title: Acne

text: Large nodules were previously called cysts. The term "nodulocystic" has been used in the medical literature to describe severe cases of inflammatory acne. True cysts are rare in those with acne, and the term "severe nodular acne" is now the preferred terminology.


title: Acne

text: "Acne inversa" (L. invertō, "upside-down") and "acne rosacea" (rosa, "rose-colored" + -āceus, "forming") are not forms of acne and are alternate names that respectively refer to the skin conditions hidradenitis suppurativa (HS) and rosacea. Although HS shares certain overlapping features with acne vulgaris, such as a tendency to clog skin follicles with skin cell debris, the condition otherwise lacks the hallmark features of acne and is therefore considered a distinct skin disorder.


title: Acne

text: Typical features of acne include increased secretion of oily sebum by the skin, microcomedones, comedones, papules, nodules (large papules), pustules, and often results in scarring. The appearance of acne varies with skin color. It may result in psychological and social problems.


title: Acne

text: Acne scars are caused by inflammation within the dermis and are estimated to affect 95% of people with acne vulgaris. Abnormal healing and dermal inflammation create the scar. Scarring is most likely to take place with severe acne but may occur with any form of acne vulgaris. Acne scars are classified based on whether the abnormal healing response following dermal inflammation leads to excess collagen deposition or loss at the site of the acne lesion.


title: Acne

text: Atrophic acne scars have lost collagen from the healing response and are the most common type of acne scar (accounting for approximately 75% of all acne scars). Ice-pick scars, boxcar scars, and rolling scars are subtypes of atrophic acne scars. Boxcar scars are round or ovoid indented scars with sharp borders and vary in size from 1.5–4 mm across. Ice-pick scars are narrow (less than 2 mm across), deep scars that extend into the dermis. Rolling scars are broader than ice-pick and boxcar scars (4–5 mm across) and have a wave-like pattern of depth in the skin.


title: Acne

text: Hypertrophic scars are uncommon and are characterized by increased collagen content after the abnormal healing response. They are described as firm and raised from the skin. Hypertrophic scars remain within the original margins of the wound, whereas keloid scars can form scar tissue outside of these borders. Keloid scars from acne occur more often in men and people with darker skin, and usually occur on the trunk of the body.


title: Acne

text: In November 2021 a study was published exposing the consensus of twenty-four renowned international plastic surgeons and dermatologists about the most effective energy-based devices for the treatment of acne scars.


title: Acne

text: After an inflamed nodular acne lesion resolves, it is common for the skin to darken in that area, which is known as postinflammatory hyperpigmentation (PIH). The inflammation stimulates specialized pigment-producing skin cells (known as melanocytes) to produce more melanin pigment, which leads to the skin's darkened appearance. PIH occurs more frequently in people with darker skin color. Pigmented scar is a common term used for PIH, but is misleading as it suggests the color change is permanent. Often, PIH can be prevented by avoiding any aggravation of the nodule and can fade with time. However, untreated PIH can last for months, years, or even be permanent if deeper layers of skin are affected. Even minimal skin exposure to the sun's ultraviolet rays can sustain hyperpigmentation. Daily use of SPF 15 or higher sunscreen can minimize such a risk.


title: Acne

text: Risk factors for the development of acne, other than genetics, have not been conclusively identified. Possible secondary contributors include hormones, infections, diet, and stress. Studies investigating the impact of smoking on the incidence and severity of acne have been inconclusive. Sunlight and cleanliness are not associated with acne.


title: Acne

text: Acne appears to be highly heritable; genetics explain 81% of the variation in the population. Studies performed in affected twins and first-degree relatives further demonstrate the strongly inherited nature of acne. Acne susceptibility is likely due to the influence of multiple genes, as the disease does not follow a classic (Mendelian) inheritance pattern. These gene candidates include certain variations in tumor necrosis factor-alpha (TNF-alpha), IL-1 alpha, and CYP1A1 genes, among others. The 308 G/A single nucleotide polymorphism variation in the gene for TNF is associated with an increased risk for acne. Acne can be a feature of rare genetic disorders such as Apert's syndrome. Severe acne may be associated with XYY syndrome.


title: Acne

text: Hormonal activity, such as occurs during menstrual cycles and puberty, may contribute to the formation of acne. During puberty, an increase in sex hormones called androgens causes the skin follicle glands to grow larger and make more oily sebum. The androgen hormones testosterone, dihydrotestosterone (DHT), and dehydroepiandrosterone (DHEA) are all linked to acne. High levels of growth hormone (GH) and insulin-like growth factor 1 (IGF-1) are also associated with worsened acne. Both androgens and IGF-1 seem to be essential for acne to occur, as acne does not develop in individuals with complete androgen insensitivity syndrome (CAIS) or Laron syndrome (insensitivity to GH, resulting in very low IGF-1 levels).


title: Acne

text: Medical conditions that commonly cause a high-androgen state, such as polycystic ovary syndrome, congenital adrenal hyperplasia, and androgen-secreting tumors, can cause acne in affected individuals. Conversely, people who lack androgenic hormones or are insensitive to the effects of androgens rarely have acne. Pregnancy can increase androgen levels, and consequently, oily sebum synthesis. Acne can be a side effect of testosterone replacement therapy or anabolic steroid use. Over-the-counter bodybuilding and dietary supplements often contain illegally added anabolic steroids.


title: Acne

text: The anaerobic bacterial species "Cutibacterium acnes" (formerly "Propionibacterium acnes") contributes to the development of acne, but its exact role is not well understood. There are specific sub-strains of "C. acnes" associated with normal skin and others with moderate or severe inflammatory acne. It is unclear whether these undesirable strains evolve on-site or are acquired, or possibly both depending on the person. These strains have the capability of changing, perpetuating, or adapting to the abnormal cycle of inflammation, oil production, and inadequate sloughing of dead skin cells from acne pores. Infection with the parasitic mite "Demodex" is associated with the development of acne. It is unclear whether eradication of the mite improves acne.


title: Acne

text: High-glycemic-load diets have been found to have different degrees of effect on acne severity. Multiple randomized controlled trials and nonrandomized studies have found a lower-glycemic-load diet to be effective in reducing acne. There is weak observational evidence suggesting that dairy milk consumption is positively associated with a higher frequency and severity of acne. Milk contains whey protein and hormones such as bovine IGF-1 and precursors of dihydrotestosterone. Studies suggest these components promote the effects of insulin and IGF-1 and thereby increase the production of androgen hormones, sebum, and promote the formation of comedones. Available evidence does not support a link between eating chocolate or salt and acne severity. Few studies have examined the relationship between obesity and acne. Vitamin B may trigger skin outbreaks similar to acne (acneiform eruptions), or worsen existing acne when taken in doses exceeding the recommended daily intake.


title: Acne

text: There are few high-quality studies to demonstrate that stress causes or worsens acne. Despite being controversial, some research indicates that increased acne severity is associated with high stress levels in certain contexts, such as hormonal changes seen in premenstrual syndrome.


title: Acne

text: Some individuals experience severe intensification of their acne when they are exposed to hot humid climates; this is due to bacteria and fungus thriving in warm, moist environments. This climate induced acne exacerbation has been termed tropical acne.


title: Acne

text: Mechanical obstruction of skin follicles with helmets or chinstraps can worsen pre-existing acne. However, when acne is caused by mechanical obstruction it is not considered a form of acne vulgaris when being very technical. It would be an other acneiform eruption known as Acne mechanica.


title: Acne

text: form of acne. Examples of such medications include lithium, hydantoin, isoniazid, glucocorticoids, iodides, bromides, and testosterone. When acne medicamentosa is specifically caused by anabolic–androgenic steroids it can simply be referred to as steroid acne.


title: Acne

text: Genetically susceptible individuals can get acne breakouts as a result of polymorphous light eruption; a condition triggered by sunlight and artificial UV light exposure. This form of acne is called Acne aestivalis and it's specifically caused by intense UVA light exposure. Affected individuals usually experience seasonal acne breakouts on their upper arms, shoulder girdle, back, and chest. The breakouts typically occur one-to-three days after they've been exposed to intese UVA radiation. Unlike other forms of acne the condition spares the face; this could possibly be a result of the pathogenesis of polymorphous light eruption, in which areas of the skin that are "newly" exposed to intense ultraviolet radiation are affected. Since faces are typically left uncovered at all stages of life there's little-to-no likelihood for an eruption to appear there. Studies show that both polymorphous light eruption outbreaks and the acne aestivalis breakout response can be prevented by topical antioxidants combined with the application of a broad spectrum sunscreen.


title: Acne

text: Acne vulgaris is a chronic skin disease of the pilosebaceous unit and develops due to blockages in the skin's hair follicles. These blockages occur as a result of the following four abnormal processes: increased oily sebum production (influenced by androgens), excessive deposition of the protein keratin leading to comedo formation, colonization of the follicle by "Cutibacterium acnes" ("C. acnes") bacteria, and the local release of pro-inflammatory chemicals in the skin.


title: Acne

text: The earliest pathologic change is the formation of a plug (a microcomedone), which is driven primarily by excessive growth, reproduction, and accumulation of skin cells in the hair follicle. In healthy skin, the skin cells that have died come up to the surface and exit the pore of the hair follicle. In people with acne, the increased production of oily sebum causes the dead skin cells to stick together. The accumulation of dead skin cell debris and oily sebum blocks the pore of the hair follicle, thus forming the microcomedone. The "C. acnes" biofilm within the hair follicle worsens this process. If the microcomedone is superficial within the hair follicle, the skin pigment melanin is exposed to air, resulting in its oxidation and dark appearance (known as a blackhead or open comedo). In contrast, if the microcomedone occurs deep within the hair follicle, this causes the formation of a whitehead (known as a closed comedo).


title: Acne

text: The main hormonal driver of oily sebum production in the skin is dihydrotestosterone. Another androgenic hormone responsible for increased sebaceous gland activity is DHEA-S. The adrenal glands secrete higher amounts of DHEA-S during adrenarche (a stage of puberty), and this leads to an increase in sebum production. In a sebum-rich skin environment, the naturally occurring and largely commensal skin bacterium "C. acnes" readily grows and can cause inflammation within and around the follicle due to activation of the innate immune system. "C. acnes" triggers skin inflammation in acne by increasing the production of several pro-inflammatory chemical signals (such as IL-1α, IL-8, TNF-α, and LTB4); IL-1α is essential to comedo formation.


title: Acne

text: "C. acnes"' ability to bind and activate a class of immune system receptors known as toll-like receptors (TLRs), especially TLR2 and TLR4, is a core mechanism of acne-related skin inflammation. Activation of TLR2 and TLR4 by "C. acnes" leads to increased secretion of IL-1α, IL-8, and TNF-α. The release of these inflammatory signals attracts various immune cells to the hair follicle, including neutrophils, macrophages, and Th1 cells. IL-1α stimulates increased skin cell activity and reproduction, which, in turn, fuels comedo development. Furthermore, sebaceous gland cells produce more antimicrobial peptides, such as HBD1 and HBD2, in response to the binding of TLR2 and TLR4.


title: Acne

text: "C. acnes" also provokes skin inflammation by altering the fatty composition of oily sebum. Oxidation of the lipid squalene by "C. acnes" is of particular importance. Squalene oxidation activates NF-κB (a protein complex) and consequently increases IL-1α levels. Additionally, squalene oxidation increases 5-lipoxygenase enzyme activity, which catalyzes the conversion of arachidonic acid to leukotriene B4 (LTB4). LTB4 promotes skin inflammation by acting on the peroxisome proliferator-activated receptor alpha (PPARα) protein. PPARα increases the activity of activator protein 1 (AP-1) and NF-κB, thereby leading to the recruitment of inflammatory T cells. "C. acnes"' ability to convert sebum triglycerides to pro-inflammatory free fatty acids via secretion of the enzyme lipase further explains its inflammatory properties. These free fatty acids spur increased production of cathelicidin, HBD1, and HBD2, thus leading to further inflammation.


title: Acne

text: This inflammatory cascade typically leads to the formation of inflammatory acne lesions, including papules, infected pustules, or nodules. If the inflammatory reaction is severe, the follicle can break into the deeper layers of the dermis and subcutaneous tissue and cause the formation of deep nodules. The involvement of AP-1 in the aforementioned inflammatory cascade activates matrix metalloproteinases, which contribute to local tissue destruction and scar formation.


title: Acne

text: Along with the bacteria "C. acnes", the bacterial species "Staphylococcus epidermidis" ("S. epidermidis") also takes a part in the physiopathology of acne vulgaris. The proliferation of "S. epidermidis" with "C. acnes" causes the formation of biofilms, which blocks the hair follicles and pores, creating an anaerobic environment under the skin. This enables for increased growth of both "C. acnes" and "S. epidermidis" under the skin. The proliferation of "C. acnes" causes the formation of biofilms and a biofilm matrix, making it even harder to treat the acne.


title: Acne

text: Acne vulgaris is diagnosed based on a medical professional's clinical judgment. The evaluation of a person with suspected acne should include taking a detailed medical history about a family history of acne, a review of medications taken, signs or symptoms of excessive production of androgen hormones, cortisol, and growth hormone. Comedones (blackheads and whiteheads) must be present to diagnose acne. In their absence, an appearance similar to that of acne would suggest a different skin disorder. Microcomedones (the precursor to blackheads and whiteheads) are not visible to the naked eye when inspecting the skin and require a microscope to be seen. Many features may indicate that a person's acne vulgaris is sensitive to hormonal influences. Historical and physical clues that may suggest hormone-sensitive acne include onset between ages 20 and 30; worsening the week before a woman's period; acne lesions predominantly over the jawline and chin; and inflammatory/nodular acne lesions.


title: Acne

text: Several scales exist to grade the severity of acne vulgaris, but disagreement persists about the ideal one for diagnostic use. Cook's acne grading scale uses photographs to grade severity from 0 to 8, with higher numbers representing more severe acne. This scale was the first to use a standardized photographic protocol to assess acne severity; since its creation in 1979, the scale has undergone several revisions. The Leeds acne grading technique counts acne lesions on the face, back, and chest and categorizes them as inflammatory or non-inflammatory. Leeds scores range from 0 (least severe) to 10 (most severe) though modified scales have a maximum score of 12. The Pillsbury acne grading scale classifies the severity of the acne from grade 1 (least severe) to grade 4 (most severe).


title: Acne

text: Many skin conditions can mimic acne vulgaris, and these are collectively known as acneiform eruptions. Such conditions include angiofibromas, epidermal cysts, flat warts, folliculitis, keratosis pilaris, milia, perioral dermatitis, and rosacea, among others. Age is one factor that may help distinguish between these disorders. Skin disorders such as perioral dermatitis and keratosis pilaris can appear similar to acne but tend to occur more frequently in childhood. Rosacea tends to occur more frequently in older adults. Facial redness triggered by heat or the consumption of alcohol or spicy food is also more suggestive of rosacea. The presence of comedones helps health professionals differentiate acne from skin disorders that are similar in appearance. Chloracne and occupational acne due to exposure to certain chemicals & industrial compounds, may look very similar to acne vulgaris.


title: Acne

text: Many different treatments exist for acne. These include alpha hydroxy acid, anti-androgen medications, antibiotics, antiseborrheic medications, azelaic acid, benzoyl peroxide, hormonal treatments, keratolytic soaps, nicotinamide, retinoids, and salicylic acid. Acne treatments work in at least four different ways, including the following: reducing inflammation, hormonal manipulation, killing "C. acnes", and normalizing skin cell shedding and sebum production in the pore to prevent blockage. Typical treatments include topical therapies such as antibiotics, benzoyl peroxide, and retinoids, and systemic therapies, including antibiotics, hormonal agents, and oral retinoids.


title: Acne

text: Recommended therapies for first-line use in acne vulgaris treatment include topical retinoids, benzoyl peroxide, and topical or oral antibiotics. Procedures such as light therapy and laser therapy are not first-line treatments and typically have only an add on role due to their high cost and limited evidence. Blue light therapy is of unclear benefit. Medications for acne target the early stages of comedo formation and are generally ineffective for visible skin lesions; acne generally improves between eight and twelve weeks after starting therapy.


title: Acne

text: People often view acne as a short-term condition, some expecting it to disappear after puberty. This misconception can lead to depending on self-management or problems with long-term adherence to treatment. Communicating the long-term nature of the condition and better access to reliable information about acne can help people know what to expect from treatments.


title: Acne

text: In general, it is recommended that people with acne do not wash affected skin more than twice daily. The application of a fragrance-free moisturizer to sensitive and acne-prone skin may reduce irritation. Skin irritation from acne medications typically peaks at two weeks after onset of use and tends to improve with continued use. Dermatologists recommend using cosmetic products that specifically say non-comedogenic, oil-free, and won't clog pores.


title: Acne

text: Acne vulgaris patients, even those with oily skin, should moisturize in order to support the skin's moisture barrier since skin barrier dysfunction may contribute to acne. Moisturizers, especially ceramide-containing moisturizers, as an adjunct therapy are particularly helpful for the dry skin and irritation that commonly results from topical acne treatment. Studies show that ceramide-containing moisturizers are important for optimal skin care; they enhance acne therapy adherence and complement existing acne therapies. In a study where acne patients used 1.2% clindamycin phosphate / 2.5% benzoyl peroxide gel in the morning and applied a micronized 0.05% tretinoin gel in the evening the overwhelming majority of patients experienced no cutaneous adverse events throughout the study. It was concluded that using ceramide cleanser and ceramide moisturizing cream caused the favorable tolerability, did not interfere with the treatment efficacy, and improved adherence to the regimen. The importance of preserving the acidic mantle and its barrier functions is widely accepted in the scientific community. Thus, maintaining a pH in the range 4.5 - 5.5 is essential in order to keep the skin surface in its optimal, healthy conditions.


title: Acne

text: Causal relationship is rarely observed with diet/nutrition and dermatologic conditions. Rather, associations — some of them compelling — have been found between diet and outcomes including disease severity and the number of conditions experienced by a patient. Evidence is emerging in support of medical nutrition therapy as a way of reducing the severity and incidence of dermatologic diseases, including acne. Researchers observed a link between high glycemic index diets and acne. Dermatologists also recommend a diet low in simple sugars as a method of improving acne. As of 2014, the available evidence is insufficient to use milk restriction for this purpose.


title: Acne

text: Benzoyl peroxide (BPO) is a first-line treatment for mild and moderate acne due to its effectiveness and mild side-effects (mainly skin irritation). In the skin follicle, benzoyl peroxide kills "C. acnes" by oxidizing its proteins through the formation of oxygen free radicals and benzoic acid. These free radicals likely interfere with the bacterium's metabolism and ability to make proteins. Additionally, benzoyl peroxide is mildly effective at breaking down comedones and inhibiting inflammation. Combination products use benzoyl peroxide with a topical antibiotic or retinoid, such as benzoyl peroxide/clindamycin and benzoyl peroxide/adapalene, respectively. Topical benzoyl peroxide is effective at treating acne.


title: Acne

text: Side effects include increased skin photosensitivity, dryness, redness, and occasional peeling. Sunscreen use is often advised during treatment, to prevent sunburn. Lower concentrations of benzoyl peroxide are just as effective as higher concentrations in treating acne but are associated with fewer side effects. Unlike antibiotics, benzoyl peroxide does not appear to generate bacterial antibiotic resistance.


title: Acne

text: Retinoids are medications that reduce inflammation, normalize the follicle cell life cycle, and reduce sebum production. They are structurally related to vitamin A. Studies show dermatologists and primary care doctors underprescribe them for acne. The retinoids appear to influence the cell life cycle in the follicle lining. This helps prevent the accumulation of skin cells within the hair follicle that can create a blockage. They are a first-line acne treatment, especially for people with dark-colored skin. Retinoids are known to lead to faster improvement of postinflammatory hyperpigmentation.


title: Acne

text: Topical retinoids include adapalene, retinol, retinaldehyde, isotretinoin, tazarotene, trifarotene, and tretinoin. They often cause an initial flare-up of acne and facial flushing and can cause significant skin irritation. Generally speaking, retinoids increase the skin's sensitivity to sunlight and are therefore recommended for use at night. Tretinoin is the least expensive of the topical retinoids and is the most irritating to the skin, whereas adapalene is the least irritating but costs significantly more. Most formulations of tretinoin are incompatible for use with benzoyl peroxide. Tazarotene is the most effective and expensive topical retinoid but is usually not as well tolerated. In 2019 a tazarotene lotion formulation, marketed to be a less irritating option, was approved by the FDA. Retinol is a form of vitamin A that has similar but milder effects and is present in many over-the-counter moisturizers and other topical products.


title: Acne

text: Isotretinoin is an oral retinoid that is very effective for severe nodular acne, and moderate acne that is stubborn to other treatments. One to two months of use is typically adequate to see improvement. Acne often resolves completely or is much milder after a 4–6 month course of oral isotretinoin. After a single round of treatment, about 80% of people report an improvement, with more than 50% reporting complete remission. About 20% of people require a second course, but 80% of those report improvement, resulting in a cumulative 96% efficacy rate.


title: Acne

text: There are concerns that isotretinoin is linked to adverse effects, like depression, suicidality, and anemia. There is no clear evidence to support some of these claims. Isotretinoin has been found in some studies to be superior to antibiotics or placebo in reducing acne lesions. However, a 2018 review comparing inflammatory lesions after treatment with antibiotics or isotretinoin found no difference. The frequency of adverse events was about twice as high with isotretinoin use, although these were mostly dryness-related events. No increased risk of suicide or depression was conclusively found.


title: Acne

text: Medical authorities strictly regulate isotretinoin use in women of childbearing age due to its known harmful effects in pregnancy. For such a woman to be considered a candidate for isotretinoin, she must have a confirmed negative pregnancy test and use an effective form of birth control. In 2008, the United States started the iPLEDGE program to prevent isotretinoin use during pregnancy. iPledge requires the woman to have two negative pregnancy tests and to use two types of birth control for at least one month before isotretinoin therapy begins and one month afterward. The effectiveness of the iPledge program is controversial due to continued instances of contraception nonadherence.


title: Acne

text: People may apply antibiotics to the skin or take them orally to treat acne. They work by killing "C. acnes" and reducing inflammation. Although multiple guidelines call for healthcare providers to reduce the rates of prescribed oral antibiotics, many providers do not follow this guidance. Oral antibiotics remain the most commonly prescribed systemic therapy for acne. Widespread broad-spectrum antibiotic overuse for acne has led to higher rates of antibiotic-resistant "C. acnes" strains worldwide, especially to the commonly used tetracycline (e.g., doxycycline) and macrolide antibiotics (e.g., topical erythromycin). Therefore, dermatologists prefer antibiotics as part of combination therapy and not for use alone.


title: Acne

text: Commonly used antibiotics, either applied to the skin or taken orally, include clindamycin, erythromycin, metronidazole, sulfacetamide, and tetracyclines (e.g., doxycycline or minocycline). Doxycycline 40 milligrams daily (low-dose) appears to have similar efficacy to 100 milligrams daily and has fewer gastrointestinal side effects. However, low-dose doxycycline is not FDA-approved for the treatment of acne. Antibiotics applied to the skin are typically used for mild to moderately severe acne. Oral antibiotics are generally more effective than topical antibiotics and produce faster resolution of inflammatory acne lesions than topical applications. Topical and oral antibiotics are not recommended for use together.


title: Acne

text: Oral antibiotics are recommended for no longer than three months as antibiotic courses exceeding this duration are associated with the development of antibiotic resistance and show no clear benefit over shorter durations. If long-term oral antibiotics beyond three months are used, then it is recommended that benzoyl peroxide or a retinoid be used at the same time to limit the risk of "C. acnes" developing antibiotic resistance.


title: Acne

text: The antibiotic dapsone is effective against inflammatory acne when applied to the skin. It is generally not a first-line choice due to its higher cost and a lack of clear superiority over other antibiotics. Topical dapsone is sometimes a preferred therapy in women or for people with sensitive or darker-toned skin. It is not recommended for use with benzoyl peroxide due to the risk of causing yellow-orange skin discoloration with this combination. Minocycline is an effective acne treatment, but it is not a first-line antibiotic due to a lack of evidence that it is better than other treatments, and concerns about its safety compared to other tetracyclines.


title: Acne

text: Sarecycline is the most recent oral antibiotic developed specifically for the treatment of acne, and is FDA-approved for the treatment of moderate to severe inflammatory acne in patients nine years of age and older. It is a narrow-spectrum tetracycline antibiotic that exhibits the necessary antibacterial activity against pathogens related to acne vulgaris and a low propensity for inducing antibiotic resistance. In clinical trials, sarecycline demonstrated clinical efficacy in reducing inflammatory acne lesions as early as three weeks and reduced truncal (back and chest) acne.


title: Acne

text: In women, the use of combined birth control pills can improve acne. These medications contain an estrogen and a progestin. They work by decreasing the production of androgen hormones by the ovaries and by decreasing the free and hence biologically active fractions of androgens, resulting in lowered skin production of sebum and consequently reduce acne severity. First-generation progestins such as norethindrone and norgestrel have androgenic properties and may worsen acne. Although oral estrogens decrease IGF-1 levels in some situations, which could theoretically improve acne symptoms, combined birth control pills do not appear to affect IGF-1 levels in fertile women. Cyproterone acetate-containing birth control pills seem to decrease total and free IGF-1 levels. Combinations containing third- or fourth-generation progestins, including desogestrel, dienogest, drospirenone, or norgestimate, as well as birth control pills containing cyproterone acetate or chlormadinone acetate, are preferred for women with acne due to their stronger antiandrogenic effects. Studies have shown a 40 to 70% reduction in acne lesions with combined birth control pills. A 2014 review found that oral antibiotics appear to be somewhat more effective than birth control pills at reducing the number of inflammatory acne lesions at three months. However, the two therapies are approximately equal in efficacy at six months for decreasing the number of inflammatory, non-inflammatory, and total acne lesions. The authors of the analysis suggested that birth control pills may be a preferred first-line acne treatment, over oral antibiotics, in certain women due to similar efficacy at six months and a lack of associated antibiotic resistance. In contrast to combined birth control pills, progestogen-only birth control forms that contain androgenic progestins have been associated with worsened acne.


title: Acne

text: Antiandrogens such as cyproterone acetate and spironolactone can successfully treat acne, especially in women with signs of excessive androgen production, such as increased hairiness or skin production of sebum, or scalp hair loss. Spironolactone is an effective treatment for acne in adult women. Unlike combined birth control pills, it is not approved by the United States Food and Drug Administration for this purpose. Spironolactone is an aldosterone antagonist and is a useful acne treatment due to its ability to additionally block the androgen receptor at higher doses. Alone or in combination with a birth control pill, spironolactone has shown a 33 to 85% reduction in acne lesions in women. The effectiveness of spironolactone for acne appears to be dose-dependent. High-dose cyproterone acetate alone reportedly decreases acne symptoms in women by 75 to 90% within three months. It is usually combined with an estrogen to avoid menstrual irregularities and estrogen deficiency. The medication appears to be effective in the treatment of acne in males, with one study finding that a high dosage reduced inflammatory acne lesions by 73%. However, spironolactone and cyproterone acetate's side effects in males, such as gynecomastia, sexual dysfunction, and decreased bone mineral density, generally make their use for male acne impractical.


title: Acne

text: Pregnant and lactating women should not receive antiandrogens for their acne due to a possibility of birth disorders such as hypospadias and feminization of male babies. Women who are sexually active and who can or may become pregnant should use an effective method of contraception to prevent pregnancy while taking an antiandrogen. Antiandrogens are often combined with birth control pills for this reason, which can result in additive efficacy. The FDA added a black-box warning to spironolactone about possible tumor risks based on preclinical research with very high doses (>100-fold clinical doses) and cautioned that unnecessary use of the medication should be avoided. However, several large epidemiological studies subsequently found no greater risk of tumors in association with spironolactone in humans. Conversely, strong associations of cyproterone acetate with certain brain tumors have been discovered and its use has been restricted. The brain tumor risk with cyproterone acetate is due to its strong progestogenic actions and is not related to antiandrogenic activity nor shared by other antiandrogens.


title: Acne

text: Flutamide, a pure antagonist of the androgen receptor, is effective in treating acne in women. It appears to reduce acne symptoms by 80 to 90% even at low doses, with several studies showing complete acne clearance. In one study, flutamide decreased acne scores by 80% within three months, whereas spironolactone decreased symptoms by only 40% in the same period. In a large long-term study, 97% of women reported satisfaction with the control of their acne with flutamide. Although effective, flutamide has a risk of serious liver toxicity, and cases of death in women taking even low doses of the medication to treat androgen-dependent skin and hair conditions have occurred. As such, the use of flutamide for acne has become increasingly limited, and it has been argued that continued use of flutamide for such purposes is unethical. Bicalutamide, a pure androgen receptor antagonist with the same mechanism as flutamide and with comparable or superior antiandrogenic efficacy but with a far lower risk of liver toxicity, is an alternative option to flutamide in the treatment of androgen-dependent skin and hair conditions in women.


title: Acne

text: Clascoterone is a topical antiandrogen that has demonstrated effectiveness in the treatment of acne in both males and females and was approved for clinical use for this indication in August 2020. It has shown no systemic absorption or associated antiandrogenic side effects. In a small direct head-to-head comparison, clascoterone showed greater effectiveness than topical isotretinoin. 5α-Reductase inhibitors such as finasteride and dutasteride may be useful for the treatment of acne in both males and females but have not been adequately evaluated for this purpose. Moreover, 5α-reductase inhibitors have a strong potential for producing birth defects in male babies and this limits their use in women. However, 5α-reductase inhibitors are frequently used to treat excessive facial/body hair in women and can be combined with birth control pills to prevent pregnancy. There is no evidence as of 2010 to support the use of cimetidine or ketoconazole in the treatment of acne.


title: Acne

text: Hormonal treatments for acne such as combined birth control pills and antiandrogens may be considered first-line therapy for acne under many circumstances, including desired contraception, known or suspected hyperandrogenism, acne during adulthood, acne that flares premenstrually, and when symptoms of significant sebum production (seborrhea) are co-present. Hormone therapy is effective for acne both in women with hyperandrogenism and in women with normal androgen levels.


title: Acne

text: Azelaic acid is effective for mild to moderate acne when applied topically at a 15–20% concentration. Treatment twice daily for six months is necessary, and is as effective as topical benzoyl peroxide 5%, isotretinoin 0.05%, and erythromycin 2%. Azelaic acid is an effective acne treatment due to its ability to reduce skin cell accumulation in the follicle and its antibacterial and anti-inflammatory properties. It has a slight skin-lightening effect due to its ability to inhibit melanin synthesis. Therefore, it is useful in treating individuals with acne who are also affected by post-inflammatory hyperpigmentation. Azelaic acid may cause skin irritation. It is less effective and more expensive than retinoids. Azelaic acid also led to worse treatment response when compared to benzoyl peroxide. When compared to tretinoin, azelaic acid makes little or no treatment response.


title: Acne

text: Salicylic acid is a topically applied beta-hydroxy acid that stops bacteria from reproducing and has keratolytic properties. It is less effective than retinoid therapy. Salicylic acid opens obstructed skin pores and promotes the shedding of epithelial skin cells. Dry skin is the most commonly seen side effect with topical application, though darkening of the skin can occur in individuals with darker skin types.


title: Acne

text: Topical and oral preparations of nicotinamide (the amide form of vitamin B) are alternative medical treatments. Nicotinamide reportedly improves acne due to its anti-inflammatory properties, its ability to suppress sebum production, and its wound healing properties. Topical and oral preparations of zinc are suggested treatments for acne; evidence to support their use for this purpose is limited. Zinc's capacities to reduce inflammation and sebum production as well as inhibit "C. acnes" growth are its proposed mechanisms for improving acne. Antihistamines may improve symptoms among those already taking isotretinoin due to their anti-inflammatory properties and their ability to suppress sebum production.


title: Acne

text: Hydroquinone lightens the skin when applied topically by inhibiting tyrosinase, the enzyme responsible for converting the amino acid tyrosine to the skin pigment melanin, and is used to treat acne-associated post-inflammatory hyperpigmentation. By interfering with the production of melanin in the epidermis, hydroquinone leads to less hyperpigmentation as darkened skin cells are naturally shed over time. Improvement in skin hyperpigmentation is typically seen within six months when used twice daily. Hydroquinone is ineffective for hyperpigmentation affecting deeper layers of skin such as the dermis. The use of a sunscreen with SPF 15 or higher in the morning with reapplication every two hours is recommended when using hydroquinone. Its application only to affected areas lowers the risk of lightening the color of normal skin but can lead to a temporary ring of lightened skin around the hyperpigmented area. Hydroquinone is generally well-tolerated; side effects are typically mild (e.g., skin irritation) and occur with the use of a higher than the recommended 4% concentration. Most preparations contain the preservative sodium metabisulfite, which has been linked to rare cases of allergic reactions, including anaphylaxis and severe asthma exacerbations in susceptible people. In extremely rare cases, the frequent and improper application of high-dose hydroquinone has been associated with a systemic condition known as exogenous ochronosis (skin discoloration and connective tissue damage from the accumulation of homogentisic acid).


title: Acne

text: Combination therapy—using medications of different classes together, each with a different mechanism of action—has been demonstrated to be a more effective approach to acne treatment than monotherapy. The use of topical benzoyl peroxide and antibiotics together is more effective than antibiotics alone. Similarly, using a topical retinoid with an antibiotic clears acne lesions faster than the use of antibiotics alone. Frequently used combinations include the following: antibiotic and benzoyl peroxide, antibiotic and topical retinoid, or topical retinoid and benzoyl peroxide. Dermatologists generally prefer combining benzoyl peroxide with a retinoid over the combination of a topical antibiotic with a retinoid. Both regimens are effective, but benzoyl peroxide does not lead to antibiotic resistance.


title: Acne

text: Although sebaceous gland activity in the skin increases during the late stages of pregnancy, pregnancy has not been reliably associated with worsened acne severity. In general, topically applied medications are considered the first-line approach to acne treatment during pregnancy, as they have little systemic absorption and are therefore unlikely to harm a developing fetus. Highly recommended therapies include topically applied benzoyl peroxide (pregnancy category C) and azelaic acid (category B). Salicylic acid carries a category C safety rating due to higher systemic absorption (9–25%), and an association between the use of anti-inflammatory medications in the third trimester and adverse effects to the developing fetus including too little amniotic fluid in the uterus and early closure of the babies' ductus arteriosus blood vessel. Prolonged use of salicylic acid over significant areas of the skin or under occlusive (sealed) dressings is not recommended as these methods increase systemic absorption and the potential for fetal harm. Tretinoin (category C) and adapalene (category C) are very poorly absorbed, but certain studies have suggested teratogenic effects in the first trimester. The data examining the association between maternal topical retinoid exposure in the first trimester of pregnancy and adverse pregnancy outcomes is limited. A systematic review of observational studies concluded that such exposure does not appear to increase the risk of major birth defects, miscarriages, stillbirths, premature births, or low birth weight. Similarly, in studies examining the effects of topical retinoids during pregnancy, fetal harm has not been seen in the second and third trimesters. Nevertheless, since rare harms from topical retinoids are not ruled out, they are not recommended for use during pregnancy due to persistent safety concerns. Retinoids contraindicated for use during pregnancy include the topical retinoid tazarotene, and oral retinoids isotretinoin and acitretin (all category X). Spironolactone is relatively contraindicated for use during pregnancy due to its antiandrogen effects. Finasteride is not recommended as it is highly teratogenic.


title: Acne

text: Topical antibiotics deemed safe during pregnancy include clindamycin, erythromycin, and metronidazole (all category B), due to negligible systemic absorption. Nadifloxacin and dapsone (category C) are other topical antibiotics that may be used to treat acne in pregnant women but have received less study. No adverse fetal events have been reported from the topical use of dapsone. If retinoids are used there is a high risk of abnormalities occurring in the developing fetus; women of childbearing age are therefore required to use effective birth control if retinoids are used to treat acne. Oral antibiotics deemed safe for pregnancy (all category B) include azithromycin, cephalosporins, and penicillins. Tetracyclines (category D) are contraindicated during pregnancy as they are known to deposit in developing fetal teeth, resulting in yellow discoloration and thinned tooth enamel. Their use during pregnancy has been associated with the development of acute fatty liver of pregnancy and is further avoided for this reason.


title: Acne

text: Limited evidence supports comedo extraction, but it is an option for comedones that do not improve with standard treatment. Another procedure for immediate relief is the injection of a corticosteroid into an inflamed acne comedo. Electrocautery and electrofulguration are effective alternative treatments for comedones.


title: Acne

text: Light therapy is a treatment method that involves delivering certain specific wavelengths of light to an area of skin affected by acne. Both regular and laser light have been used. The evidence for light therapy as a treatment for acne is weak and inconclusive. Various light therapies appear to provide a short-term benefit, but data for long-term outcomes, and outcomes in those with severe acne, are sparse; it may have a role for individuals whose acne has been resistant to topical medications. A 2016 meta-analysis was unable to conclude whether light therapies were more beneficial than placebo or no treatment, nor the duration of benefit.


title: Acne

text: When regular light is used immediately following the application of a sensitizing substance to the skin such as aminolevulinic acid or methyl aminolevulinate, the treatment is referred to as photodynamic therapy (PDT). PDT has the most supporting evidence of all light therapy modalities. PDT treats acne by using various forms of light (e.g., blue light or red light) that preferentially target the pilosebaceous unit. Once the light activates the sensitizing substance, this generates free radicals and reactive oxygen species in the skin, which purposefully damage the sebaceous glands and kill "C. acnes" bacteria. Many different types of nonablative lasers (i.e., lasers that do not vaporize the top layer of the skin but rather induce a physiologic response in the skin from the light) have been used to treat acne, including those that use infrared wavelengths of light. Ablative lasers (such as CO and fractional types) have also been used to treat active acne and its scars. When ablative lasers are used, the treatment is often referred to as laser resurfacing because, as mentioned previously, the entire upper layers of the skin are vaporized. Ablative lasers are associated with higher rates of adverse effects compared with non-ablative lasers, with examples being post-inflammatory hyperpigmentation, persistent facial redness, and persistent pain. Physiologically, certain wavelengths of light, used with or without accompanying topical chemicals, are thought to kill bacteria and decrease the size and activity of the glands that produce sebum. Disadvantages of light therapy can include its cost, the need for multiple visits, the time required to complete the procedure(s), and pain associated with some of the treatment modalities. Typical side effects include skin peeling, temporary reddening of the skin, swelling, and post-inflammatory hyperpigmentation.


title: Acne

text: Dermabrasion is an effective therapeutic procedure for reducing the appearance of superficial atrophic scars of the boxcar and rolling varieties. Ice-pick scars do not respond well to treatment with dermabrasion due to their depth. The procedure is painful and has many potential side effects such as skin sensitivity to sunlight, redness, and decreased pigmentation of the skin. Dermabrasion has fallen out of favor with the introduction of laser resurfacing. Unlike dermabrasion, there is no evidence that microdermabrasion is an effective treatment for acne.


title: Acne

text: Dermal or subcutaneous fillers are substances injected into the skin to improve the appearance of acne scars. Fillers are used to increase natural collagen production in the skin and to increase skin volume and decrease the depth of acne scars. Examples of fillers used for this purpose include hyaluronic acid; poly(methyl methacrylate) microspheres with collagen; human and bovine collagen derivatives, and fat harvested from the person's own body (autologous fat transfer).


title: Acne

text: Microneedling is a procedure in which an instrument with multiple rows of tiny needles is rolled over the skin to elicit a wound healing response and stimulate collagen production to reduce the appearance of atrophic acne scars in people with darker skin color. Notable adverse effects of microneedling include post-inflammatory hyperpigmentation and tram track scarring (described as discrete slightly raised scars in a linear distribution similar to a tram track). The latter is thought to be primarily attributable to improper technique by the practitioner, including the use of excessive pressure or inappropriately large needles.


title: Acne

text: Subcision is useful for the treatment of superficial atrophic acne scars and involves the use of a small needle to loosen the fibrotic adhesions that result in the depressed appearance of the scar.


title: Acne

text: Chemical peels can be used to reduce the appearance of acne scars. Mild peels include those using glycolic acid, lactic acid, salicylic acid, Jessner's solution, or a lower concentration (20%) of trichloroacetic acid. These peels only affect the epidermal layer of the skin and can be useful in the treatment of superficial acne scars as well as skin pigmentation changes from inflammatory acne. Higher concentrations of trichloroacetic acid (30–40%) are considered to be medium-strength peels and affect the skin as deep as the papillary dermis. Formulations of trichloroacetic acid concentrated to 50% or more are considered to be deep chemical peels. Medium-strength and deep-strength chemical peels are more effective for deeper atrophic scars but are more likely to cause side effects such as skin pigmentation changes, infection, and small white superficial cysts known as milia.


title: Acne

text: Researchers are investigating complementary therapies as treatment for people with acne. Low-quality evidence suggests topical application of tea tree oil or bee venom may reduce the total number of skin lesions in those with acne. Tea tree oil appears to be approximately as effective as benzoyl peroxide or salicylic acid but is associated with allergic contact dermatitis. Proposed mechanisms for tea tree oil's anti-acne effects include antibacterial action against "C. acnes" and anti-inflammatory properties. Numerous other plant-derived therapies have demonstrated positive effects against acne (e.g., basil oil; oligosaccharides from seaweed; however, few well-done studies have examined their use for this purpose. There is a lack of high-quality evidence for the use of acupuncture, herbal medicine, or cupping therapy for acne.


title: Acne

text: Many over-the-counter treatments in many forms are available, which are often known as cosmeceuticals. Certain types of makeup may be useful to mask acne. In those with oily skin, a water-based product is often preferred.


title: Acne

text: Acne usually improves around the age of 20 but may persist into adulthood. Permanent physical scarring may occur. Rare complications from acne or its treatment include the formation of pyogenic granulomas, osteoma cutis, and acne with facial edema. Early and aggressive treatment of acne is advocated by some in the medical community to reduce the chances of these poor outcomes.


title: Acne

text: There is good evidence to support the idea that acne and associated scarring negatively affect a person's psychological state, worsen mood, lower self-esteem, and are associated with a higher risk of anxiety disorders, depression, and suicidal thoughts.


title: Acne

text: Misperceptions about acne's causative and aggravating factors are common, and people with acne often blame themselves, and others often blame those with acne for their condition. Such blame can worsen the affected person's sense of self-esteem. Until the 20th century, even among dermatologists, the list of causes was believed to include excessive sexual thoughts and masturbation. Dermatology's association with sexually transmitted infections, especially syphilis, contributed to the stigma.


title: Acne

text: Another psychological complication of acne vulgaris is acne excoriée, which occurs when a person persistently picks and scratches pimples, irrespective of the severity of their acne. This can lead to significant scarring, changes in the affected person's skin pigmentation, and a cyclic worsening of the affected person's anxiety about their appearance.


title: Acne

text: Globally, acne affects approximately 650 million people, or about 9.4% of the population, as of 2010. It affects nearly 90% of people in Western societies during their teenage years, but can occur before adolescence and may persist into adulthood. While acne that first develops between the ages of 21 and 25 is uncommon, it affects 54% of women and 40% of men older than 25 years of age and has a lifetime prevalence of 85%. About 20% of those affected have moderate or severe cases. It is slightly more common in females than males (9.8% versus 9.0%). In those over 40 years old, 1% of males and 5% of females still have problems.


title: Acne

text: Rates appear to be lower in rural societies. While some research has found it affects people of all ethnic groups, acne may not occur in the non-Westernized peoples of Papua New Guinea and Paraguay.


title: Acne

text: Acne affects 40–50 million people in the United States (16%) and approximately 3–5 million in Australia (23%). Severe acne tends to be more common in people of Caucasian or Amerindian descent than in people of African descent.


title: Acne

text: Historical records indicate Pharaohs had acne, which may be the earliest known reference to the disease. Sulfur's usefulness as a topical remedy for acne dates back to at least the reign of Cleopatra (69–30 BCE). The sixth-century Greek physician Aëtius of Amida reportedly coined the term "" (,) or "", which seems to be a reference to facial skin lesions that occur during "the 'acme' of life" (puberty).


title: Acne

text: In the 16th century, the French physician and botanist François Boissier de Sauvages de Lacroix provided one of the earlier descriptions of acne. He used the term "psydracia achne" to describe small, red, and hard tubercles that altered a person's facial appearance during adolescence and were neither itchy nor painful.


title: Acne

text: The recognition and characterization of acne progressed in 1776 when Josef Plenck (an Austrian physician) published a book that proposed the novel concept of classifying skin diseases by their elementary (initial) lesions. In 1808 the English dermatologist Robert Willan refined Plenck's work by providing the first detailed descriptions of several skin disorders using morphologic terminology that remains in use today. Thomas Bateman continued and expanded on Robert Willan's work as his student and provided the first descriptions and illustrations of acne accepted as accurate by modern dermatologists. Erasmus Wilson, in 1842, was the first to make the distinction between acne vulgaris and rosacea. The first professional medical monograph dedicated entirely to acne was written by Lucius Duncan Bulkley and published in New York in 1885.


title: Acne

text: Scientists initially hypothesized that acne represented a disease of the skin's hair follicle, and occurred due to blockage of the pore by sebum. During the 1880s, they observed bacteria by microscopy in skin samples from people with acne. Investigators believed the bacteria caused comedones, sebum production, and ultimately acne. During the mid-twentieth century, dermatologists realized that no single hypothesized factor (sebum, bacteria, or excess keratin) fully accounted for the disease in its entirety. This led to the current understanding that acne could be explained by a sequence of related events, beginning with blockage of the skin follicle by excessive dead skin cells, followed by bacterial invasion of the hair follicle pore, changes in sebum production, and inflammation.


title: Acne

text: The approach to acne treatment underwent significant changes during the twentieth century. Retinoids became a medical treatment for acne in 1943. Benzoyl peroxide was first proposed as a treatment in 1958 and remains a staple of acne treatment. The introduction of oral tetracycline antibiotics (such as minocycline) modified acne treatment in the 1950s. These reinforced the idea amongst dermatologists that bacterial growth on the skin plays an important role in causing acne. Subsequently, in the 1970s, tretinoin (original trade name Retin A) was found to be an effective treatment. The development of oral isotretinoin (sold as Accutane and Roaccutane) followed in 1980. After its introduction in the United States, scientists identified isotretinoin as a medication highly likely to cause birth defects if taken during pregnancy. In the United States, more than 2,000 women became pregnant while taking isotretinoin between 1982 and 2003, with most pregnancies ending in abortion or miscarriage. Approximately 160 babies were born with birth defects due to maternal use of isotretinoin during pregnancy.


title: Acne

text: Treatment of acne with topical crushed dry ice, known as cryoslush, was first described in 1907 but is no longer performed commonly. Before 1960, the use of X-rays was also a common treatment.


title: Acne

text: The costs and social impact of acne are substantial. In the United States, acne vulgaris is responsible for more than 5 million doctor visits and costs over  billion each year in direct costs. Similarly, acne vulgaris is responsible for 3.5 million doctor visits each year in the United Kingdom. Sales for the top ten leading acne treatment brands in the US in 2015 amounted to $352million.


title: Acne

text: Acne vulgaris and its resultant scars are associated with significant social and academic difficulties that can last into adulthood. During the Great Depression, dermatologists discovered that young men with acne had difficulty obtaining jobs. Until the 1930s, many people viewed acne as a trivial problem among middle-class girls because, unlike smallpox and tuberculosis, no one died from it, and a feminine problem, because boys were much less likely to seek medical assistance for it. During World War II, some soldiers in tropical climates developed such severe and widespread tropical acne on their bodies that they were declared medically unfit for duty.


title: Acne

text: Efforts to better understand the mechanisms of sebum production are underway. This research aims to develop medications that target and interfere with the hormones that are known to increase sebum production (e.g., IGF-1 and alpha-melanocyte-stimulating hormone). Other sebum-lowering medications such as topical antiandrogens, peroxisome proliferator-activated receptor modulators, and inhibitors of the stearoyl-CoA desaturase-1 enzyme are also a focus of research efforts. Particles that release nitric oxide into the skin to decrease skin inflammation caused by "C. acnes" and the immune system have shown promise for improving acne in early clinical trials. Another avenue of early-stage research has focused on how to best use laser and light therapy to selectively destroy sebum-producing glands in the skin's hair follicles to reduce sebum production and improve acne appearance.


title: Acne

text: The use of antimicrobial peptides against "C. acnes" is under investigation as a treatment for acne to overcoming antibiotic resistance. In 2007, scientists reported the first genome sequencing of a "C. acnes" bacteriophage (PA6). The authors proposed applying this research toward the development of bacteriophage therapy as an acne treatment to overcome the problems associated with long-term antibiotic use, such as bacterial resistance. Oral and topical probiotics are under evaluation as treatments for acne. Probiotics may have therapeutic effects for those affected by acne due to their ability to decrease skin inflammation and improve skin moisture by increasing the skin's ceramide content. As of 2014, knowledge of the effects of probiotics on acne in humans was limited.


title: Acne

text: Decreased levels of retinoic acid in the skin may contribute to comedo formation. Researchers are investigating methods to increase the skin's production of retinoic acid to address this deficiency. A vaccine against inflammatory acne has shown promising results in mice and humans. Some have voiced concerns about creating a vaccine designed to neutralize a stable community of normal skin bacteria that is known to protect the skin from colonization by more harmful microorganisms.


title: Aktion T4

text: The killings took place from September 1939 until the end of the war in 1945; from 275,000 to 300,000 people were killed in psychiatric hospitals in Germany and Austria, occupied Poland and the Protectorate of Bohemia and Moravia (now the Czech Republic). The number of victims was originally recorded as 70,273 but this number has been increased by the discovery of victims listed in the archives of the former East Germany. About half of those killed were taken from church-run asylums, often with the approval of the Protestant or Catholic authorities of the institutions.


title: Aktion T4

text: The Holy See announced on 2 December 1940 that the policy was contrary to divine law and that "the direct killing of an innocent person because of mental or physical defects is not allowed" but the declaration was not upheld by all Catholic authorities in Germany. In the summer of 1941, protests were led in Germany by the Bishop of Münster, Clemens von Galen, whose intervention led to "the strongest, most explicit and most widespread protest movement against any policy since the beginning of the Third Reich", according to Richard J. Evans.


title: Aktion T4

text: Several reasons have been suggested for the killings, including eugenics, racial hygiene, and saving money. Physicians in German and Austrian asylums continued many of the practices of until the defeat of Germany in 1945, in spite of its official cessation in August 1941. The informal continuation of the policy led to 93,521 "beds emptied" by the end of 1941. Technology developed under , particularly the use of lethal gas on large numbers of people, was taken over by the medical division of the Reich Interior Ministry, along with the personnel of , who participated in mass murder of Jewish people. The programme was authorised by Hitler but the killings have since come to be viewed as murders in Germany. The number of people killed was about 200,000 in Germany and Austria, with about 100,000 victims in other European countries. Following the war, a number of the perpetrators were tried and convicted for murder and crimes against humanity.


title: Aktion T4

text: At the beginning of the twentieth century, the sterilisation of people carrying what were considered to be hereditary defects and in some cases those exhibiting what was thought to be hereditary "antisocial" behaviour, was a respectable field of medicine. Canada, Denmark, Switzerland and the US had passed laws enabling coerced sterilisation. Studies conducted in the 1920s ranked Germany as a country that was unusually reluctant to introduce sterilisation legislation. In his book "Mein Kampf" (1924), Hitler wrote that one day racial hygiene "will appear as a deed greater than the most victorious wars of our present bourgeois era".


title: Aktion T4

text: In July 1933, the "Law for the Prevention of Hereditarily Diseased Offspring" prescribed compulsory sterilisation for people with conditions thought to be hereditary, such as schizophrenia, epilepsy, Huntington's chorea and "imbecility". Sterilisation was also legalised for chronic alcoholism and other forms of social deviance. The law was administered by the Interior Ministry under Wilhelm Frick through special Hereditary Health Courts (), which examined the inmates of nursing homes, asylums, prisons, aged-care homes and special schools, to select those to be sterilised. It is estimated that 360,000 people were sterilised under this law between 1933 and 1939.


title: Aktion T4

text: The policy and research agenda of racial hygiene and eugenics were promoted by Emil Kraepelin. The eugenic sterilisation of persons diagnosed with (and viewed as predisposed to) schizophrenia was advocated by Eugen Bleuler, who presumed racial deterioration because of "mental and physical cripples" in his "Textbook of Psychiatry",


title: Aktion T4

text: Within the Nazi administration, the idea of including in the programme people with physical disabilities had to be expressed carefully, because the Reich Minister of Propaganda, Joseph Goebbels, had a deformed right leg. After 1937, the acute shortage of labour in Germany arising from rearmament, meant that anyone capable of work was deemed to be "useful", exempted from the law and the rate of sterilisation declined. The term is a post-war coining; contemporary German terms included (euthanasia) and (merciful death). The T4 programme stemmed from the Nazi Party policy of "racial hygiene", a belief that the German people needed to be cleansed of racial enemies, which included anyone confined to a mental health facility and people with simple physical disabilities. New insulin shock treatments were used by German psychiatrists to find out if patients with schizophrenia were curable.


title: Aktion T4

text: Karl Brandt, doctor to Hitler and Hans Lammers, the head of the Reich Chancellery, testified after the war that Hitler had told them as early as 1933—when the sterilisation law was passed—that he favoured the killing of the incurably ill but recognised that public opinion would not accept this. In 1935, Hitler told the Leader of Reich Doctors, Gerhard Wagner, that the question could not be taken up in peacetime; "Such a problem could be more smoothly and easily carried out in war". He wrote that he intended to "radically solve" the problem of the mental asylums in such an event. began with a "trial" case in late 1938. Hitler instructed Brandt to evaluate a petition sent by two parents for the "mercy killing" of their son who was blind and had physical and developmental disabilities. The child, born near Leipzig and eventually identified as Gerhard Kretschmar, was killed in July 1939. Hitler instructed Brandt to proceed in the same manner in all similar cases.


title: Aktion T4

text: On 18 August 1939, three weeks after the killing of the boy, the "Reich Committee for the Scientific Registering of Hereditary and Congenital Illnesses" was established to register sick children or newborns identified as defective. The secret killing of infants began in 1939 and increased after the war started; by 1941, more than 5,000 children had been killed. Hitler was in favour of killing those whom he judged to be ('Life unworthy of life'). A few months before the "euthanasia" decree, in a 1939 conference with Leonardo Conti, Reich Health Leader and State Secretary for Health in the Interior Ministry, and Hans Lammers, Chief of the Reich Chancellery, Hitler gave as examples the mentally ill who he said could only be "bedded on sawdust or sand" because they "perpetually dirtied themselves" and "put their own excrement into their mouths". This issue, according to the Nazi regime, assumed a new urgency in wartime.


title: Aktion T4

text: Pfannmüller advocated killing by a gradual decrease of food, which he believed was more merciful than poison injections.


title: Aktion T4

text: The German eugenics movement had an extreme wing even before the Nazis came to power. As early as 1920, Alfred Hoche and Karl Binding advocated killing people whose lives were "unworthy of life" (). Darwinism was interpreted by them as justification of the demand for "beneficial" genes and eradication of the "harmful" ones. Robert Lifton wrote, "The argument went that the best young men died in war, causing a loss to the of the best genes. The genes of those who did not fight (the worst genes) then proliferated freely, accelerating biological and cultural degeneration". The advocacy of eugenics in Germany gained ground after 1930, when the Depression was used to excuse cuts in funding to state mental hospitals, creating squalor and overcrowding.


title: Aktion T4

text: Many German eugenicists were nationalists and antisemites, who embraced the Nazi regime with enthusiasm. Many were appointed to positions in the Health Ministry and German research institutes. Their ideas were gradually adopted by the majority of the German medical profession, from which Jewish and communist doctors were soon purged. During the 1930s, the Nazi Party had carried out a campaign of propaganda in favour of euthanasia. The National Socialist Racial and Political Office (NSRPA) produced leaflets, posters and short films to be shown in cinemas, pointing out to Germans the cost of maintaining asylums for the incurably ill and insane. These films included "The Inheritance" (, 1935), "The Victim of the Past" (, 1937), which was given a major première in Berlin and was shown in all German cinemas, and "I Accuse" (, 1941) which was based on a novel by Hellmuth Unger, a consultant for "child euthanasia".


title: Aktion T4

text: In mid-1939, Hitler authorised the creation of the Reich Committee for the Scientific Registering of Serious Hereditary and Congenital Illnesses () led by his physician, Karl Brandt, administered by Herbert Linden of the Interior Ministry, leader of German Red Cross Ernst-Robert Grawitz and SS- Viktor Brack. Brandt and Bouhler were authorised to approve applications to kill children in relevant circumstances, though Bouhler left the details to subordinates such as Brack and SA- Werner Blankenburg.


title: Aktion T4

text: Extermination centres were established at six existing psychiatric hospitals: Bernburg, Brandenburg, Grafeneck, Hadamar, Hartheim, and Sonnenstein. One thousand children under the age of 17 were killed at the institutions Am Spiegelgrund and Gugging in Austria. They played a crucial role in developments leading to the Holocaust. As a related aspect of the "medical" and scientific basis of this programme, the Nazi doctors took thousands of brains from 'euthanasia' victims for research.


title: Aktion T4

text: From August 1939, the Interior Ministry registered children with disabilities, requiring doctors and midwives to report all cases of newborns with severe disabilities; the 'guardian' consent element soon disappeared. Those to be killed were identified as "all children under three years of age in whom any of the following 'serious hereditary diseases' were 'suspected': idiocy and Down syndrome (especially when associated with blindness and deafness); microcephaly; hydrocephaly; malformations of all kinds, especially of limbs, head, and spinal column; and paralysis, including spastic conditions". The reports were assessed by a panel of medical experts, of whom three were required to give their approval before a child could be killed.


title: Aktion T4

text: The Ministry used deceit when dealing with parents or guardians, particularly in Catholic areas, where parents were generally uncooperative. Parents were told that their children were being sent to "Special Sections", where they would receive improved treatment. The children sent to these centres were kept for "assessment" for a few weeks and then killed by injection of toxic chemicals, typically phenol; their deaths were recorded as "pneumonia". Autopsies were usually performed and brain samples were taken to be used for "medical research". Post mortem examinations apparently helped to ease the consciences of many of those involved, giving them the feeling that there was a genuine medical purpose to the killings. The most notorious of these institutions in Austria was Am Spiegelgrund, where from 1940 to 1945, 789 children were killed by lethal injection, gas poisoning and physical abuse. Children's brains were preserved in jars of formaldehyde and stored in the basement of the clinic and in the private collection of Heinrich Gross, one of the institution's directors, until 2001.


title: Aktion T4

text: When the Second World War began in September 1939, less rigorous standards of assessment and a quicker approval process were adopted. Older children and adolescents were included and the conditions covered came to include


title: Aktion T4

text: More pressure was placed on parents to agree to their children being sent away. Many parents suspected what was happening and refused consent, especially when it became apparent that institutions for children with disabilities were being systematically cleared of their charges. The parents were warned that they could lose custody of all their children and if that did not suffice, the parents could be threatened with call-up for 'labour duty'. By 1941, more than 5,000 children had been killed. The last child to be killed under was Richard Jenne on 29 May 1945, in the children's ward of the Kaufbeuren-Irsee state hospital in Bavaria, Germany, more than three weeks after US Army troops had occupied the town.


title: Aktion T4

text: Brandt and Bouhler developed plans to expand the programme of euthanasia to adults. In July 1939 they held a meeting attended by Conti and Professor Werner Heyde, head of the SS medical department. This meeting agreed to arrange a national register of all institutionalised people with mental illnesses or physical disabilities. The first adults with disabilities to be killed en masse by the Nazi regime were Poles. After the invasion on 1 September 1939, adults with disabilities were shot by the SS men of 16, and under the command of SS- Rudolf Tröger, with overall command by Reinhard Heydrich, during the genocidal Operation Tannenberg.


title: Aktion T4

text: All hospitals and mental asylums of the Wartheland were emptied. The region was incorporated into Germany and earmarked for resettlement by following the German conquest of Poland. In the Danzig (now Gdańsk) area, some 7,000 Polish patients of various institutions were shot and 10,000 were killed in the Gdynia area. Similar measures were taken in other areas of Poland destined for incorporation into Germany. The first experiments with the gassing of patients were conducted in October 1939 at Fort VII in Posen (occupied Poznań), where hundreds of prisoners were killed by means of carbon monoxide poisoning, in an improvised gas chamber developed by Albert Widmann, chief chemist of the German Criminal Police (Kripo). In December 1939, Heinrich Himmler witnessed one of these gassings, ensuring that this invention would later be put to much wider uses.


title: Aktion T4

text: The idea of killing adult mental patients soon spread from occupied Poland to adjoining areas of Germany, probably because Nazi Party and SS officers in these areas were most familiar with what was happening in Poland. These were also the areas where Germans wounded from the Polish campaign were expected to be accommodated, which created a demand for hospital space. The of Pomerania, Franz Schwede-Coburg, sent 1,400 patients from five Pomeranian hospitals to undisclosed locations in occupied Poland, where they were shot. The of East Prussia, Erich Koch, had 1,600 patients killed out of sight. More than 8,000 Germans were killed in this initial wave of killings carried out on the orders of local officials, although Himmler certainly knew and approved of them.


title: Aktion T4

text: The legal basis for the programme was a 1939 letter from Hitler, not a formal "Führer's decree" with the force of law. Hitler bypassed Conti, the Health Minister and his department, who might have raised questions about the legality of the programme and entrusted it to Bouhler and Brandt.


title: Aktion T4

text: The killings were administered by Viktor Brack and his staff from 4, disguised as the "Charitable Foundation for Cure and Institutional Care" offices which served as the front and was supervised by Bouhler and Brandt. The officials in charge included Herbert Linden, who had been involved in the child killing programme; Ernst-Robert Grawitz, chief physician of the SS and August Becker, an SS chemist. The officials selected the doctors who were to carry out the operational part of the programme; based on political reliability as long-term Nazis, professional reputation and sympathy for radical eugenics. The list included physicians who had proved their worth in the child-killing programme, such as Unger, Heinze and Hermann Pfannmüller. The recruits were mostly psychiatrists, notably Professor Carl Schneider of Heidelberg, Professor Max de Crinis of Berlin and Professor Paul Nitsche from the Sonnenstein state institution. Heyde became the operational leader of the programme, succeeded later by Nitsche.


title: Aktion T4

text: In early October, all hospitals, nursing homes, old-age homes and sanatoria were required to report all patients who had been institutionalised for five years or more, who had been committed as "criminally insane", who were of "non-Aryan race" or who had been diagnosed with any on a list of conditions. The conditions included schizophrenia, epilepsy, Huntington's chorea, advanced syphilis, senile dementia, paralysis, encephalitis and "terminal neurological conditions generally". Many doctors and administrators assumed that the reports were to identify inmates who were capable of being drafted for "labour service" and tended to overstate the degree of incapacity of their patients, to protect them from labour conscription. When some institutions refused to co-operate, teams of T4 doctors (or Nazi medical students) visited and compiled the lists, sometimes in a haphazard and ideologically motivated way. During 1940, all Jewish patients were removed from institutions and killed.


title: Aktion T4

text: As with child inmates, adults were assessed by a panel of experts, working at the offices. The experts were required to make their judgements on the reports, not medical histories or examinations. Sometimes they dealt with hundreds of reports at a time. On each they marked a + (death), a - (life), or occasionally a ? meaning that they were unable to decide. Three "death" verdicts condemned the person and as with reviews of children, the process became less rigorous, the range of conditions considered "unsustainable" grew broader and zealous Nazis further down the chain of command increasingly made decisions on their own initiative.


title: Aktion T4

text: The first gassings in Germany proper took place in January 1940 at the Brandenburg Euthanasia Centre. The operation was headed by Brack, who said "the needle belongs in the hand of the doctor". Bottled pure carbon monoxide gas was used. At trials, Brandt described the process as a "major advance in medical history". Once the efficacy of the method was confirmed, it became standard and was instituted at a number of centres in Germany under the supervision of Widmann, Becker and Christian Wirth – a Kripo officer who later played a prominent role in the Final Solution (extermination of Jews) as commandant of newly built death camps in occupied Poland. In addition to Brandenburg, the killing centres included Grafeneck Castle in Baden-Württemberg (10,824 dead), Schloss Hartheim near Linz in Austria (over 18,000 dead), Sonnenstein in Saxony (15,000 dead), Bernburg in Saxony-Anhalt and Hadamar in Hesse (14,494 dead). The same facilities were also used to kill mentally sound prisoners transferred from concentration camps in Germany, Austria and occupied parts of Poland.


title: Aktion T4

text: Condemned patients were transferred from their institutions to new centres in T4 Charitable Ambulance buses, called the Community Patients Transports Service. They were run by teams of SS men wearing white coats, to give it an air of medical care. To prevent the families and doctors of the patients from tracing them, the patients were often first sent to transit centres in major hospitals, where they were supposedly assessed. They were moved again to "special treatment" () centres. Families were sent letters explaining that owing to wartime regulations, it was not possible for them to visit relatives in these centres. Most of these patients were killed within 24 hours of arriving at the centres and their bodies cremated. For every person killed, a death certificate was prepared, giving a false but plausible cause of death. This was sent to the family along with an urn of ashes (random ashes, since the victims were cremated ). The preparation of thousands of falsified death certificates took up most of the working day of the doctors who operated the centres.


title: Aktion T4

text: During 1940, the centres at Brandenburg, Grafeneck and Hartheim killed nearly 10,000 people each, while another 6,000 were killed at Sonnenstein. In all, about 35,000 people were killed in T4 operations that year. Operations at Brandenburg and Grafeneck were wound up at the end of the year, partly because the areas they served had been cleared and partly because of public opposition. In 1941, however, the centres at Bernburg and Sonnenstein increased their operations, while Hartheim (where Wirth and Franz Stangl were successively commandants) continued as before. Another 35,000 people were killed before August 1941, when the T4 programme was officially shut down by Hitler. Even after that date the centres continued to be used to kill concentration camp inmates: eventually some 20,000 people in this category were killed.


title: Aktion T4

text: In 1971, Gitta Sereny conducted interviews with Stangl, who was in prison in Düsseldorf, after having been convicted of co-responsibility for killing 900,000 people, while commandant of the Sobibor and Treblinka extermination camps in Poland. Stangl gave Sereny a detailed account of the operations of the T4 programme based on his time as commandant of the killing facility at the Hartheim institute. He described how the inmates of various asylums were removed and transported by bus to Hartheim. Some were in no mental state to know what was happening to them but many were perfectly sane and for them various forms of deception were used. They were told they were at a special clinic where they would receive improved treatment and were given a brief medical examination on arrival. They were induced to enter what appeared to be a shower block, where they were gassed with carbon monoxide (the ruse was also used at extermination camps).


title: Aktion T4

text: The SS functionaries and hospital staff associated with in the German Reich were paid from the central office at 4 in Berlin from the spring of 1940. The SS and police from responsible for murdering the majority of patients in the annexed territories of Poland since October 1939, took their salaries from the normal police fund, supervised by the administration of the newly formed "Wartheland" district; the programme in Germany and occupied Poland was overseen by Heinrich Himmler. Before 2013, it was believed that 70,000 persons were murdered in the euthanasia programme, but the German Federal Archives reported that research in the archives of former East Germany indicated that the number of victims in Germany and Austria from 1939 to 1945 was about 200,000 persons and that another 100,000 persons were victims in other European countries. In the German T4 centres there was at least the semblance of legality in keeping records and writing letters. In Polish psychiatric hospitals no one was left behind. Killings were inflicted using gas-vans, sealed army bunkers and machine guns; families were not informed about the murdered relatives and the empty wards were handed over to the SS.


title: Aktion T4

text: After the official end of the euthanasia programme in 1941, most of the personnel and high-ranking officials, as well as gassing technology and the techniques used to deceive victims, were transferred under the jurisdiction of the national medical division of the Reich Interior Ministry. Further gassing experiments with the use of mobile gas chambers () were conducted at Soldau concentration camp by Herbert Lange following Operation Barbarossa. Lange was appointed commander of the Chełmno extermination camp in December 1941. He was given three gas vans by the Reich Security Main Office (RSHA), converted by the Gaubschat GmbH in Berlin and before February 1942, killed 3,830 Polish Jews and around 4,000 Romani, under the guise of "resettlement". After the Wannsee conference, implementation of gassing technology was accelerated by Heydrich. Beginning in the spring of 1942, three killing factories were built secretly in east-central Poland. The "SS" officers responsible for the earlier , including Wirth, Stangl and Irmfried Eberl, had important roles in the implementation of the "Final Solution" for the next two years. The first killing centre equipped with stationary gas chambers modelled on technology developed under was established at Bełżec in the General Government territory of occupied Poland; the decision preceded the Wannsee Conference of January 1942 by three months.


title: Aktion T4

text: In January 1939, Brack commissioned a paper from Professor of Moral Theology at the University of Paderborn, Joseph Mayer, on the likely reactions of the churches in the event of a state euthanasia programme being instituted. Mayera longstanding euthanasia advocatereported that the churches would not oppose such a programme if it was seen to be in the national interest. Brack showed this paper to Hitler in July and it may have increased his confidence that the "euthanasia" programme would be acceptable to German public opinion. Notably, when Sereny interviewed Mayer shortly before his death in 1967, he denied that he formally condoned the killing of people with disabilities but no copies of this paper are known to survive.


title: Aktion T4

text: Some bureaucrats opposed the T4 programme; Lothar Kreyssig, a district judge and member of the Confessing Church, wrote to Gürtner protesting that the action was illegal since no law or formal decree from Hitler had authorised it. Gürtner replied, "If you cannot recognise the will of the Führer as a source of law, then you cannot remain a judge" and had Kreyssig dismissed. Hitler had a policy of not issuing written instructions for matters which could later be condemned by the international community but made an exception when he provided Bouhler and Brack with written authority for the T4 programme. Hitler wrote a confidential letter in October 1939 to overcome opposition within the German state bureaucracy. Hitler told Bouhler that, "the Führer's Chancellery must under no circumstances be seen to be active in this matter". The Justice Minister, Franz Gürtner, had to be shown Hitler's letter in August 1940 to gain his co-operation.


title: Aktion T4

text: In the towns where the killing centres were located, some people saw the inmates arrive in buses, saw smoke from the crematoria chimneys and noticed that the buses were returning empty. In Hadamar, ashes containing human hair rained down on the town and despite the strictest orders, some of the staff at the killing centres talked about what was going on. In some cases families could tell that the causes of death in certificates were false, e.g. when a patient was claimed to have died of appendicitis, even though his appendix had been removed some years earlier. In other cases, families in the same town would receive death certificates on the same day. In May 1941, the Frankfurt County Court wrote to Gürtner describing scenes in Hadamar, where children shouted in the streets that people were being taken away in buses to be gassed.


title: Aktion T4

text: During 1940, rumours of what was taking place spread and many Germans withdrew their relatives from asylums and sanatoria to care for them at home, often with great expense and difficulty. In some places doctors and psychiatrists co-operated with families to have patients discharged or if the families could afford it, transferred them to private clinics beyond the reach of T4. Other doctors "re-diagnosed" patients so that they no longer met the T4 criteria, which risked exposure when Nazi zealots from Berlin conducted inspections. In Kiel, Professor Hans Gerhard Creutzfeldt managed to save nearly all of his patients. Lifton listed a handful of psychiatrists and administrators who opposed the killings; many doctors collaborated, either through ignorance, agreement with Nazi eugenicist policies or fear of the regime.


title: Aktion T4

text: Protest letters were sent to the Reich Chancellery and the Ministry of Justice, some from Nazi Party members. The first open protest against the removal of people from asylums took place at Absberg in Franconia in February 1941 and others followed. The SD report on the incident at Absberg noted that "the removal of residents from the Ottilien Home has caused a great deal of unpleasantness" and described large crowds of Catholic townspeople, among them Party members, protesting against the action. Similar petitions and protests occurred throughout Austria as rumours spread of mass killings at the Hartheim Euthanasia Centre and of mysterious deaths at the children's clinic, in Vienna. Anna Wödl, a nurse and mother of a child with a disability, vehemently petitioned to Hermann Linden at the Reich Ministry of the Interior in Berlin to prevent her son, Alfred, from being transferred from Gugging, where he lived and which also became a euthanasia center. Wödl failed and Alfred was sent to , where he was killed on 22 February 1941. His brain was preserved in formaldehyde for "research" and stored in the clinic for sixty years.


title: Aktion T4

text: The Lutheran theologian Friedrich von Bodelschwingh (director of the Bethel Institution for Epilepsy at Bielefeld) and Pastor Paul-Gerhard Braune (director of the Hoffnungstal Institution near Berlin) protested. Bodelschwingh negotiated directly with Brandt and indirectly with Hermann Göring, whose cousin was a prominent psychiatrist. Braune had meetings with Gürtner, who was always dubious about the legality of the programme. Gürtner later wrote a strongly worded letter to Hitler protesting against it; Hitler did not read it but was told about it by Lammers. Bishop Theophil Wurm, presiding over the Evangelical-Lutheran Church in Württemberg, wrote to Interior Minister Frick in March 1940 and that month a confidential report from the (SD) in Austria, warned that the killing programme must be implemented with stealth "...to avoid a probable backlash of public opinion during the war". On 4 December 1940, Reinhold Sautter, the Supreme Church Councillor of the Württemberg State Church, complained to the Nazi Ministerial Councillor Eugen Stähle against the murders in Grafeneck Castle. Stähle said "The fifth commandment Thou shalt not kill, is no commandment of God but a Jewish invention".


title: Aktion T4

text: Bishop Heinrich Wienken of Berlin, a leading member of the Caritas Association, was selected by the Fulda episcopal synod to represent the views of the Catholic Church in meetings with T4 operatives. In 2008, Michael Burleigh wrote


title: Aktion T4

text: Despite a decree issued by the Vatican on 2 December 1940 stating that the T4 policy was "against natural and positive Divine law" and that "The direct killing of an innocent person because of mental or physical defects is not allowed", the Catholic Church hierarchy in Germany decided to take no further action. Incensed by the Nazi appropriation of Church property in Münster to accommodate people made homeless by an air raid, in July and August 1941, the Bishop of Münster, Clemens August Graf von Galen, gave four sermons criticising the Nazis for arresting Jesuits, confiscating church property and for the euthanasia program. Galen sent the text to Hitler by telegram, calling on


title: Aktion T4

text: Galen's sermons were not reported in the German press but were circulated illegally in leaflets. The text was dropped by the Royal Air Force over German troops. In 2009, Richard J. Evans wrote that "This was the strongest, most explicit and most widespread protest movement against any policy since the beginning of the Third Reich". Local Nazis asked for Galen to be arrested but Goebbels told Hitler that such action would provoke a revolt in Westphalia and Hitler decided to wait until after the war to take revenge.


title: Aktion T4

text: In 1986, Lifton wrote, "Nazi leaders faced the prospect of either having to imprison prominent, highly admired clergymen and other protesters – a course with consequences in terms of adverse public reaction they greatly feared – or else end the programme". Evans considered it "at least possible, even indeed probable" that the T4 programme would have continued beyond Hitler's initial quota of 70,000 deaths but for the public reaction to Galen's sermon. Burleigh called assumptions that the sermon affected Hitler's decision to suspend the T4 programme "wishful thinking" and noted that the various Church hierarchies did not complain after the transfer of T4 personnel to . Henry Friedlander wrote that it was not the criticism from the Church but rather the loss of secrecy and "general popular disquiet about the way euthanasia was implemented" that caused the killings to be suspended.


title: Aktion T4

text: Galen had detailed knowledge of the euthanasia programme by July 1940 but did not speak out until almost a year after Protestants had begun to protest. In 2002, Beth A. Griech-Polelle wrote:


title: Aktion T4

text: On 29 June 1943, Pope Pius XII issued the encyclical , in which he condemned the fact that "physically deformed people, mentally disturbed people and hereditarily ill people have at times been robbed of their lives" in Germany. Following this, in September 1943, a bold but ineffectual condemnation was read by bishops from pulpits across Germany, denouncing the killing of "the innocent and defenceless mentally handicapped and mentally ill, the incurably infirm and fatally wounded, innocent hostages and disarmed prisoners of war and criminal offenders, people of a foreign race or descent".


title: Aktion T4

text: On 24 August 1941, Hitler ordered the suspension of the T4 killings. After the invasion of the Soviet Union in June, many T4 personnel were transferred to the eastern front. The projected death total for the T4 programme of 70,000 deaths had been reached by August 1941. The termination of the T4 programme did not end the killing of people with disabilities; from the end of 1941, on the initiative of institute directors and local party leaders, the killing of adults and children continued, albeit less systematically, until the end of the war. After the bombing of Hamburg in July 1943, occupants of old age homes were killed. In the post-war trial of Dr. Hilda Wernicke, Berlin, August 1946, testimony was given that "500 old, broken women" who had survived the bombing of Stettin in June 1944 were euthanised at the Meseritz-Oberwalde Asylum. The Hartheim, Bernberg, Sonnenstein and Hardamar centres continued in use as "wild euthanasia" centres to kill people sent from all over Germany, until 1945. The methods were lethal injection or starvation, those employed before use of gas chambers. By the end of 1941, about 100,000 people had been killed in the T4 programme. From mid-1941, concentration camp prisoners too feeble or too much trouble to keep alive were murdered after a cursory psychiatric examination under Action 14f13.


title: Aktion T4

text: After the war a series of trials was held in connection with the Nazi euthanasia programme at various places including: Dresden, Frankfurt, Graz, Nuremberg and Tübingen. In December 1946 an American military tribunal (commonly called the Doctors' trial) prosecuted 23 doctors and administrators for their roles in war crimes and crimes against humanity. These crimes included the systematic killing of those deemed "unworthy of life", including people with mental disabilities, the people who were institutionalised mentally ill, and people with physical impairments. After 140 days of proceedings, including the testimony of 85 witnesses and the submission of 1,500 documents, in August 1947 the court pronounced 16 of the defendants guilty. Seven were sentenced to death; the men, including Brandt and Brack, were executed on 2 June 1948.


title: Aktion T4

text: Earlier, in 1945, American forces tried seven staff members of the Hadamar killing centre for the killing of Soviet and Polish nationals, which was within their jurisdiction under international law, as these were the citizens of wartime allies. (Hadamar was within the American Zone of Occupation in Germany. This was before the Allied resolution of December 1945, to prosecute individuals for "crimes against humanity" for such mass atrocities.) Alfons Klein, Heinrich Ruoff and Karl Willig were sentenced to death and executed; the other four were given long prison sentences. In 1946, reconstructed German courts tried members of the Hadamar staff for the murders of nearly 15,000 German citizens there. The chief physician, Adolf Wahlmann and Irmgard Huber, the head nurse, were convicted.


title: Aktion T4

text: The Stasi (Ministry for State Security) of East Germany stored around 30,000 files of in their archives. Those files became available to the public after German Reunification in 1990, leading to a new wave of research on these wartime crimes.


title: Aktion T4

text: The German national memorial to the people with disabilities murdered by the Nazis was dedicated in 2014 in Berlin. It is located in the pavement of a site next to the Tiergarten park, the location of the former villa at Tiergartenstraße 4 in Berlin, where more than 60 Nazi bureaucrats and doctors worked in secret under the "T4" programme to organise the mass murder of sanatorium and psychiatric hospital patients deemed unworthy to live.


title: The Honourable

text: The Honourable (British English) or The Honorable (American English; see spelling differences) (abbreviation: Hon., Hon'ble, or variations) is an honorific style that is used as a prefix before the names or titles of certain people, usually with official governmental or diplomatic positions.


title: The Honourable

text: In international diplomatic relations, representatives of foreign states are often styled as "The Honourable". Deputy chiefs of mission, , consuls-general and consuls are always given the style. All heads of consular posts, whether they are honorary or career postholders, are accorded the style according to the State Department of the United States. However, the style "Excellency" instead of "The Honourable" is used for ambassadors and high commissioners.