The correct answer is 3. In the inguinal region, the lymph nodes can acquire a size of up to 1.5 cm being normal. In addition, the rest of the data of the inguinal exploration (no pain, mobile, soft, etc.) corroborates this. On the other hand, there are no signs or symptoms that make us think of a sexually transmitted infection.

[HIDDEN] In the inguinal region, the lymph nodes can acquire a size of up to 1.5 cm being normal. In addition, the rest of the data of the inguinal exploration (no pain, mobile, soft, etc.) corroborates this. On the other hand, there are no signs or symptoms that make us think of a sexually transmitted infection.

A 24-year-old woman consults after noticing inguinal lymphadenopathies. The interrogation does not show any local discomfort or data suggestive of sexually transmitted infection. The examination revealed two lymphadenopathies, one in each groin, 1 cm in diameter, soft, mobile, non-painful. No skin lesions are seen on the lower limbs, anus or perineum. Which test do you consider essential?

A lupus serology since it is most likely a Treponema pallidum infection.

A gynecological examination to rule out ovarian cancer.

From the clinical features it seems to be normal lymph nodes and complementary explorations should not be performed.

A Paul-Bunell test should be performed to rule out infectious mononucleosis.

Genital ulcer

Overview A genital ulcer may be located on the vulva, penis, perianal region, or anus. Globally, the incidence of genital ulcers is estimated to be approximately 20 million cases annually. The most likely cause of a genital ulcer varies depending on the characteristics of a population and location. The most common cause of genital ulcers in the United States is herpes simplex infections, with syphilis the second most common cause, and chancroid the third. These common causes of genital ulcer disease (HSV-1, HSV-2 and treponema pallidum) can all be efficiently transmitted through oral sex. Important signs associated with genital ulcers that may assist in the diagnosis of the cause of the genital ulcer may include the presence of tender or non-tender enlarged lymph nodes in the groin area, a painful or non-painful genital ulcer, or the presence of vesicular lesions, which are small, painful, elevated blisters.

Inguinal lymph nodes

Clinical significance The presence of swollen inguinal lymph nodes is an important clinical sign because lymphadenopathy (swelling) may indicate an infection, or spread as a metastasis from cancers, such as anal cancer and vulvar cancer. Inguinal lymph nodes may normally be up to 2 cm. The cut-off value for normal sized inguinal nodes is up to 10 mm. Additional images References Lymphatic organ anatomy

Inguinal lymphadenopathy

Inguinal lymphadenopathy causes swollen lymph nodes in the groin area. It can be a symptom of infective or neoplastic processes. Infective aetiologies include Tuberculosis, HIV, non-specific or reactive lymphadenopathy to recent lower limb infection or groin infections. Another notable infectious cause is Lymphogranuloma venereum, which is a sexually transmitted infection of the lymphatic system. Neoplastic aetiologies include lymphoma, leukaemia and metastatic disease from primary tumours in the lower limb, external genitalia or perianal region and melanoma. References Further reading Inflammations Diseases of veins, lymphatic vessels and lymph nodes

Lymphogranuloma venereum

The secondary stage most often occurs 10–30 days later, but can present up to six months later. The infection spreads to the lymph nodes through lymphatic drainage pathways. The most frequent presenting clinical manifestation of LGV among males whose primary exposure was genital is unilateral (in two-thirds of cases) lymphadenitis and lymphangitis, often with tender inguinal and/or femoral lymphadenopathy because of the drainage pathway for their likely infected areas. Lymphangitis of the dorsal penis may also occur and resembles a string or cord. If the route was anal sex, the infected person may experience lymphadenitis and lymphangitis noted above. They may instead develop proctitis, inflammation limited to the rectum (the distal 10–12 cm) that may be associated with anorectal pain, tenesmus, and rectal discharge, or proctocolitis, inflammation of the colonic mucosa extending to 12 cm above the anus and associated with symptoms of proctitis plus diarrhea or abdominal cramps.

InternalMed_Harrison

Diagnosis Although most genital ulcerations cannot be diagnosed confidently on clinical grounds alone, clinical findings (Table 163-7) FIGURE 163-5 Chancroid: multiple, painful, punched-out ulcers with undermined borders on the labia occurring after autoinoculation. Sexually Transmitted Infections: Overview and Clinical Approach FIGURE 163-6 Genital herpes. A relatively mild, superficial ulcer is typically seen in episodic outbreaks. (Courtesy of Michael Remington, University of Washington Virology Research Clinic.) FIGURE 163-7 Lymphogranuloma venereum (LGV): striking ten-der lymphadenopathy occurring at the femoral and inguinal lymph nodes, separated by a groove made by Poupart’s ligament. This “sign-of-the-groove” is not considered specific for LGV; for example, lym-phomas may present with this sign. InITIAL MAnAgEMEnT of gEnITAL oR PERIAnAL uLCER

Anatomy, Abdomen and Pelvis: Female External Genitalia -- Clinical Significance -- Sexually Transmitted Infections

Treponema pallidum : Syphilis infections result from Treponema pallidum . This infection usually manifests as a painless chancre in the primary stage. If the disease is left untreated, it will progress to the secondary stage. In the secondary stage, it manifests as fever, widespread maculopapular skin rashes involving the palms and soles,  widespread lymphadenopathy (epitrochlear node is pathognomic), and genital lesions similar to genital warts (condylomata lata- has a rounder surface when compared with condylomata acuminata). If there is still no treatment during the secondary stage, the infection will progress into the tertiary stage. The tertiary stage causes necrotic lesions called Gummas, neurological symptoms such as tabes dorsalis, Argyll Robertson pupils, and general paresis, cardiac symptoms such as aortitis. The treatment of syphilis is with the use of penicillin.

Gynecology_Novak

Several clinical presentations are highly suggestive of specific diagnoses: 1. A painless and minimally tender ulcer, not accompanied by inguinal lymphadenopathy, is likely to be syphilis, especially if the ulcer is indurated. A nontreponemal rapid plasma reagin (RPR) test, or venereal disease research laboratory (VDRL) test, and a confirmatory treponemal test—ﬂuorescent treponemal antibody absorption (FTA ABS) or microhemagglutinin–T. pallidum (MHA TP)—should be used to diagnose syphilis presumptively. Some laboratories screen samples with treponemal enzyme immunoassay (EIA) tests, the results of which should be confirmed with nontreponemal tests. The results of nontreponemal tests usually correlate with disease activity and should be reported quantitatively. 2.

Sexually Transmitted Infections -- History and Physical -- Granuloma Inguinale

Females and males: Signs and symptoms: Patients will present with highly vascularized lesions over the genitals and perineum that tend to be painless. [37] [38] It can cause severe scarring. Physical Exam: Typical findings include ulcer-like lesions that are beefy red, consistent with high vascularization that bleeds easily with manipulation. Subcutaneous granulomas may be present, but lymphadenopathy is uncommon. The lesions tend to be relatively large and irregular. It is often found to be associated with secondary infections. Four main lesions can be seen on examination: 1. Ulcerovegetative: large painless ulcer on the patient's physical exam. 2. Nodular: soft and erythematous that tend to ulcerate throughout the infectious process. 3. Cicatricial: dry ulcerations that tend to transition into plaques. 4. Hypertrophic: lesions are thick and painless. [37] [39]

[A chancre instead of cancer].

Syphilis (lues) is a sexually transmitted infection caused by the spirochete Treponema pallidum. In adolescents, the diagnosis of primary syphilis can be made promptly by taking a sexual medical history and inspecting the glans penis. A 17-year-old male was referred to the paediatric oncology centre for additional diagnostics due to inguinal lymphadenopathy, with a strong suspicion of a malignant lymphoma. None of the physicians took a sexual medical history or investigated the glans penis, as a result of which essential information was lacking. The combination of inguinal lymphadenopathy and the ultrasound findings for the inguinal region made the physicians only consider a malignancy. However, it actually concerned a reactive lymphadenopathy associated with primary syphilis. This case demonstrates that a full medical history and thorough physical examination can prevent the need for costly and invasive diagnostics.

Anatomy, Abdomen and Pelvis: Inguinal Lymph Node -- Clinical Significance -- Lymphadenopathy

Syphilis is a bacterial infection caused by the spirochete Treponema pallidum. Clinical presentation of secondary syphilis can present with diffuse lymphadenopathy along with fever, skin rashes, and condylomata lata. [7] Chancroid

InternalMed_Harrison

node is an enlarged left supraclavicular node infiltrated with metastatic cancer from a gastrointestinal primary. Metastases to supraclavicular nodes also occur from lung, breast, testis, or ovarian cancers. Tuberculosis, sarcoidosis, and toxoplasmosis are nonneoplastic causes of supraclavicular adenopathy. Axillary adenopathy is usually due to injuries or localized infections of the ipsilateral upper extremity. Malignant causes include melanoma or lymphoma and, in women, breast cancer. Inguinal lymphadenopathy is usually secondary to infections or trauma of the lower extremities and may accompany sexually transmitted diseases such as lymphogranuloma venereum, primary syphilis, genital herpes, or chancroid. These nodes may also be involved by lymphomas and metastatic cancer from primary lesions of the rectum, genitalia, or lower extremities (melanoma).

InternalMed_Harrison

Approach to the Patient with an Infectious Disease regions (e.g., popliteal, inguinal, epitrochlear, axillary, multiple cervical regions), with notation of the location, size (normal, <1 cm), presence or absence of tenderness, and consistency (soft, firm, or shotty) and of whether the nodes are matted (i.e., connected and moving together). Of note, palpable epitrochlear nodes are always pathologic. Of patients presenting with lymphadenopathy, 75% have localized findings, and the remaining 25% have generalized lymphadenopathy (i.e., that involving more than one anatomic region). Localized lymphadenopathy in the head and neck region is found in 55% of patients, inguinal lymphadenopathy in 14%, and axillary lymphadenopathy in 5%. Determining whether the patient has generalized versus localized lymphadenopathy can help narrow the differential diagnosis, as various infections present differently.

Swollen lymph nodes usually indicate infection from bacteria or viruses. Swollen inguinal lymph nodes could indicate an infection of areas of the lower body. One of the more concerning causes of inguinal lymphadenopathy is sexually transmitted infections. Sexually transmitted infections that commonly presents with inguinal lymphadenopathy are lymphogranuloma venereum, secondary syphilis, and chancroid caused by Chlamydia trachomatis (L1-L3), Treponema pallidum , and Haemophilus ducreyi , respectively. Lymphogranuloma venereum

Sexually Transmitted Infections -- History and Physical -- Chancroid

Females and males: Signs and symptoms: Often occurs in the 20 to 30-year-old age group, frequently among sex workers and their clients. The areas most often affected include the distal portion of the penis in men, while in women, the vagina, labia, and perianal regions are involved. The most significant symptom is the extremely high pain level noted when the lesion reaches the ulcerative stage. [6] Physical Exam: The lesion starts as a reddish papule which rapidly progresses to a pustule followed by an extremely painful ulcer. The ulcer sometimes called a "soft chancre," will have soft and irregular margins with a friable base and a grayish-yellowish exudate. It tends to bleed easily. The ulcers are typically 1 cm to 2 cm in diameter and usually resolve spontaneously within three months, even if left untreated. Close to half of the affected individuals will develop regional lymphadenopathy, which may be tender. A minority (about 25%) of these patients will progress to infected bulla or abscesses, which can rupture and become superinfected leading to significant tissue destruction and damage to the genitalia. It is estimated that 10% of affected individuals will also have syphilis or genital herpes as well.

Anatomy, Abdomen and Pelvis: Inguinal Lymph Node -- Introduction

The inguinal lymph node can be subdivided into the superficial and deep lymph nodes and collectively drains the anal canal(below the pectinate line), the skin below the umbilicus, lower extremity, scrotum, vulva, glans penis, and clitoris. The lymph node's primary function is to filter for harmful substances as lymphatic fluids travel through its cortex, paracortex, and medulla. Clinical signs of inguinal lymphadenopathy can help to clue physicians in possible diagnoses of sexually transmitted diseases such as syphilis, chancroid, and lymphogranuloma venereum. The lymph node can also serve to assist in the diagnosis of cancer.

Yaws

Serological tests cannot distinguish yaws from the closely related syphilis; no test distinguishing yaws from syphilis is widely available. The two genomes differ by about 0.2%. PCR and DNA sequencing can distinguish the two. There are also no common blood tests which distinguish among the four treponematoses: syphilis (Treponema pallidum pallidum), yaws (Treponema pallidum pertenue), bejel (Treponema pallidum endemicum), and pinta (Treponema carateum). Haemophilus ducreyi infections can cause skin conditions that mimic primary yaws. People infected with Haemophilus ducreyi lesions may or may not also have latent yaws, and thus may or may not test positive on serological tests. This was discovered in the mid 2010s. It seems that a recently diverged strain of Haemophilus ducreyi has evolved from being a sexually transmitted infection to being a skin ulcer pathogen that looks like yaws. Yaws has been reported in nonendemic countries.

Disseminated lupus vulgaris.

A 28-year-old woman presented with reddish raised, shiny lesions over the face and ears present for the past 3 years. Four years ago, she developed in her left axilla a nodule that became fluctuant and tender, which ruptured to discharge seropurulent material. It subsided after the patient had received antibiotics for 6 months, leaving puckered scarring. There was no history of antituberculous treatment. After 1 year, she developed papulonodular lesions on her face, nose, and ears. There was now a history of malaise, fever, dry cough, and anorexia and weight loss for the past 2 months. The patient was fully vaccinated in childhood, including against varicella infection. The general physical examination revealed lymphadenopathy involving cervical, axillary, and inguinal lymph nodes 0.5 x 0.5 cm to 1 x 1.5 cm, firm in consistency, and nontender. They were discrete except in the left axilla where multiple matted lymph nodes were present with overlying scarring and a papule. Her systemic examination was normal. Cutaneous examination showed a shiny erythematous plaque 3x2 cm with central atrophy and scarring on the face (Figure). It was comprised of multiple shiny nontender soft papules arranged in annular configuration. Similar discrete papules and nodules with adherent fine scaling were seen bilaterally on the alar prominence of the nose, lower lip, and post-auricular area. On diascopy, apple jelly nodules were seen. The hemogram, liver function tests, and renal function tests were normal, except for an elevated erythrocyte sedimentation rate. The Mantoux test showed erythema and an induration of 20 x 20 cm. A posteroanterior view on the chest x-ray showed fibrotic changes suggestive of pulmonary tuberculosis. Ultrasonography of the abdomen and pelvis showed no tubercular foci. Human immunodeficiency virus serology by enzyme-linked immunosorbent assay with 3 different kits was nonreactive. Histopathology from a nodule showed a focally thinned-out epidermis with follicular plugging and multiple epithelioid cell granulomas, rimmed by lymphocytes in the deeper portion of the dermis, mainly peri-appendageal. Stain for acid-fast bacteria was negative. Cultures from the skin lesions were negative. The patient was diagnosed as having lupus vulgaris with multiple lesions of varying morphology at different sites with pulmonary tuberculosis and healed lymph node involvement.

Sexually Transmitted Infections -- History and Physical -- Lymphogranuloma venereum (LGV)

Females and males: Signs and symptoms: Patients will present with painful lymphadenopathy localized to the inguinal area. Patients may note the initial presentation of a pustule that gradually progresses to large painful ulceration. [41] Men tend to present with early or acute stages, while women typically present much later. [19] Physical Exam: Lymphogranuloma venereum presents with two stages: Primary phase is a small painless papule/pustule that will ulcerate and can be visualized throughout the affected genital area. During the secondary phase, patients present with unilateral lymphadenopathy that is fluctuant with palpation or may be suppurative in a presentation known as buboes. [38] Buboes tend to rupture in the acute phase and progress to a thickened mass. [42]

InternalMed_Harrison

Lymphadenopathy may be an incidental finding in patients being examined for various reasons, or it may be a presenting sign or symptom of the patient’s illness. The physician must eventually decide whether the lymphadenopathy is a normal finding or one that requires further study, up to and including biopsy. Soft, flat, submandibular nodes (<1 cm) are often palpable in healthy children and young adults; healthy adults may have palpable inguinal nodes of up to 2 cm, which are considered normal. Further evaluation of these normal nodes is not warranted. In contrast, if the physician believes the node(s) to be abnormal, then pursuit of a more precise diagnosis is needed. APPROACH TO THE PATIENT:

Cervical lymphadenopathy

Cervical lymphadenopathy is a sign or a symptom, not a diagnosis. The causes are varied, and may be inflammatory, degenerative, or neoplastic. In adults, healthy lymph nodes can be palpable (able to be felt), in the axilla, neck and groin. In children up to the age of 12 cervical nodes up to 1 cm in size may be palpable and this may not signify any disease. If nodes heal by resolution or scarring after being inflamed, they may remain palpable thereafter. In children, most palpable cervical lymphadenopathy is reactive or infective. In individuals over the age of 50, metastatic enlargement from cancers (most commonly squamous cell carcinomas) of the aerodigestive tract should be considered. Classification Cervical lymphadenopathy can be thought of as local where only the cervical lymph nodes are affected, or general where all the lymph nodes of the body are affected. Causes

InternalMed_Harrison

adenopathy that is sometimes mistaken for malignancy; syphilis, LGV, HSV infection, and chancroid involving the anus can produce inguinal adenopathy because anal lymphatics drain to inguinal lymph nodes.

Unusual Manifestations of Secondary Syphilis: Case Presentations.

Dear Editor, Syphilis is an infection caused by Treponema pallidum. Without treatment, it goes through the following stages: primary, secondary, latent, and tertiary (1). The clinical picture of secondary syphilis is very variable (2,3). We present two rare cases of secondary syphilis, one with nodular lesions initially considered to be lymphoma and second with periostitis, which was initially interpreted as an osteoma. To date, only 15 cases with nodular lesions and 10 cases with periostitis in secondary syphilis have been reported in the literature. The first patient was a 59 year old man who presented in a private practice with nodular lesions on the face and axillary and inguinal folds (Figure 1, a, b). The initial diagnostic consideration was lymphoma. A biopsy specimen was taken, and the histopathological features revealed epidermal hyperplasia with papillomatosis, minimal spongiosis with many neutrophils and with a marked inflammatory infiltrate in dermis, consisting of lymphocytes, plasma cells, and neutrophils; the diagnosis of interfaced dermatitis was established (Figure 1, d, e). After one month, the patient presented to our clinic with numerous nodular lesions, some of them painful, located on the trunk and intertriginous folds, including the intergluteal cleft - the lesions in this area being suggestive of condylomata lata (Figure 1, c). The diagnosis of secondary syphilis was taken into consideration, and screening serum tests were performed and found reactive: a Venereal Diseases Research Laboratory (VDRL) titer of 1:64 and Treponema pallidum Hemaglutination Assay (TPHA) titer of 1:80. Hepatitis and anti-human immunodeficiency virus (HIV) antibodies serology was negative. The biopsy was repeated and showed the same histopathological changes. In addition, Warthin-Starry staining was performed, revealing the presence of some spiral micro-organisms in the dermis corresponding to Treponema pallidum (Figure 1, f). A diagnosis of secondary syphilis was established, and the patient was treated with benzathine penicillin G 2.4 million units by intramuscular injection once a week for 2 consecutive weeks. The skin lesions regressed within 1 month, and serological tests showed a VDRL titer of 1:8 3 months after treatment. The second patient was a homosexual male, 35 years old, diagnosed with HIV infection, stage B2. He presented with bone pain in the calves and forearms, with insidious onset. He also presented with an associated erythematous maculo-papular rash on the trunk and limbs and generalized lymphadenopathy (Figure 2, a, b). The tibial crest and radius were sensitive to palpation. A right leg radiography was performed, raising suspicion of osteoid osteoma. The CT scan excluded the diagnosis of osteoma; taking into account the epidemiological context, the diagnosis of syphilis was suspected. The diagnosis was confirmed by leg ultrasound examination (2D US) which showed thickening of the compact tibial bone associated with subperiosteal destructive and proliferative changes (Figure 2, c, d) and by serology for syphilis: the VDRL titer was 1:32 and the TPHA titer was 1:80. The patient was treated with benzathine penicillin 2.4 million units, once a week, for 2 consecutive weeks, with clinical improvement. Syphilis continues to be a serious public health problem worldwide, even if it is a controllable disease due to diagnostic tests and effective and accessible treatment. According to the World Health Organization in 2008, the estimated number of new cases of sexually transmitted diseases in adults with syphilis is 10.6 million cases (4). The cases presented in this paper were characterized by unusual manifestations, requiring good collaboration between the dermatologist and other specialties. In the first case, the diagnosis of secondary syphilis was confirmed by positive serological, clinical, and histopathological findings. The main differential diagnosis of nodular syphilis includes lymphoma, sarcoidosis, Kaposi's sarcoma, atypical mycobacteriosis, deep fungal infections, leprosy, tuberculosis, leishmaniasis, and lymphomatoid papulosis (5). Another important differential diagnosis is between secondary and tertiary syphilis, especially when ulcerating nodules are present. Tertiary syphilis is characterized by unilateral, deep ulcerating nodules with necrotizing granulomas (6). Bone involvement during syphilis is mainly represented by polyarthritis, synovitis, osteitis, and periostitis (7,8). Syphilitic periostitis is characterized by localized or diffuse pain, particularly during the night, which is relieved by movement. The skull, the shoulder girdle, and the long bones are the most common sites of involvement (9). In conclusion, we presented two different cases of secondary syphilis that contribute to the clinical experience of rare cases presented in the literature, raising the awareness of dermatologists and other specialists about less specific clinical aspects of syphilis.

Lymphadenopathy

Lymph node enlargement is recognized as a common sign of infectious, autoimmune, or malignant disease. Examples may include: Reactive: acute infection (e.g., bacterial, or viral), or chronic infections (tuberculous lymphadenitis, cat-scratch disease). The most distinctive sign of bubonic plague is extreme swelling of one or more lymph nodes that bulge out of the skin as "buboes." The buboes often become necrotic and may even rupture. Infectious mononucleosis is an acute viral infection usually caused by Epstein-Barr virus and may be characterized by a marked enlargement of the cervical lymph nodes. It is also a sign of cutaneous anthrax and Human African trypanosomiasis Toxoplasmosis, a parasitic disease, gives a generalized lymphadenopathy (Piringer-Kuchinka lymphadenopathy). Plasma cell variant of Castleman's disease - associated with HHV-8 infection and HIV infection

Chancroid

About half of infected men have only a single ulcer. Women frequently have four or more ulcers, with fewer symptoms. The ulcers are typically confined to the genital region most of the time. The initial ulcer may be mistaken as a "hard" chancre, the typical sore of primary syphilis, as opposed to the "soft chancre" of chancroid. Approximately one-third of the infected individuals will develop enlargements of the inguinal lymph nodes, the nodes located in the fold between the leg and the lower abdomen. Half of those who develop swelling of the inguinal lymph nodes will progress to a point where the nodes rupture through the skin, producing draining abscesses. The swollen lymph nodes and abscesses are often referred to as buboes.

Sézary disease

Generalized erythroderma– redness of the skin Lymphadenopathy – swollen, enlarged lymph nodes Atypical T-cells – malignant lymphocytes known as "Sézary cells" seen in the peripheral blood with typical cerebriform nuclei (brain-shaped, convoluted nuclei) Hepatosplenomegaly– enlarged liver and spleen Palmoplantar keratoderma – thickening of the palms of the hands, and soles of the feet Diagnosis Those who have Sézary disease often present with skin lesions that do not heal with normal medication. A blood test generally reveals any change in the levels of lymphocytes in the blood, which is often associated with a cutaneous T-cell lymphoma. Finally, a biopsy of a skin lesion can be performed to rule out any other causes.

Gynecology_Novak

3. One to three extremely painful ulcers, accompanied by tender inguinal lymphadenopathy, are unlikely to be anything except chancroid. This is especially true if the adenopathy is ﬂuctuant. 4. An inguinal bubo accompanied by one or several ulcers is most likely chancroid. If no ulcer is present, the most likely diagnosis is LGV. Recommended regimens for the treatment of chancroid include azithromycin, 1 g orally in a single dose; ceftriaxone, 250 mg intramuscularly in a single dose; ciproﬂoxacin, 500 mg orally twice a day for 3 days; or erythromycin base, 500 mg orally four times daily for 7 days. Patients should be reexamined 3 to 7 days after initiation of therapy to ensure the gradual resolution of the genital ulcer, which can be expected to heal within 2 weeks unless it is unusually large.

Scrotal lymphangioma circumscriptum.

Lymphangioma circumscriptum (LC) is anuncommon, benign, cutaneous disorder thatinvolves lymphatic dilatation to cause vesicularand papular lesions on the trunk, extremities, andanogenital areas. It may be a diagnostic challengewhen appearing in the anogenital region andoften is misdiagnosed and mistreated as infectiousetiologies, which include molluscum contagiosumand condylomata accuminata. We report a healthy40-year-old man with a six-month history of aneruption of multiple, asymptomatic, scrotal papulesthat were diagnosed as lymphangiomas. Awarenessof scrotal LC in adult men without prior disease orsymptoms is necessary for proper diagnosis andavoidance of unnecessary treatment.

Primary syphilis of the oropharynx: an unusual location of a chancre.

A 33-year-old man presented with a two-week history of an asymptomatic ulcer of the oropharynx and submandibular lymph nodes swelling. Laboratory examinations were normal, but serological tests revealed positivity for rapid plasma reagin, Treponema pallidum haemagglutination assay and anti-T. pallidum IgM antibodies. Since the patient denied any homosexual relationship, a biopsy of the lesion was performed, which confirmed primary syphilis. The patient received an intramuscular injection of Benzathine Penicillin G (2.4 MU) with complete resolution of the lesion. Extragenital chancres occur in at least 5% of patients with primary syphilis, and the oral mucosa is the most frequent location as a consequence of orogenital/oroanal contact with an infectious lesion. Because of their transient nature, these oral ulcerations are often underestimated by the patient or by any unsuspecting clinician. Health professionals should consider the recent sexual history of their patients and should be prepared to recognise oral and systemic manifestations of sexually transmitted infections.

InternalMed_Harrison

The presentation of chancroid does not usually include all of the typical clinical features and is sometimes atypical. Multiple ulcers can coalesce to form giant ulcers. Ulcers can appear and then resolve, with inguinal adenitis (Fig. 182-2) and suppuration following 1–3 weeks later; this clinical picture can be confused with that of lymphogranuloma venereum (Chap. 213). Multiple small ulcers can resemble folliculitis. Other differential diagnostic considerations include the various infections causing genital ulceration, such as primary syphilis, secondary syphilis (condyloma latum), genital herpes, and donovanosis. In rare cases, chancroid lesions become secondarily infected with bacteria; the result is extensive inflammation. FIGURE 182-2 Chancroid with characteristic penile ulcers and associated left inguinal adenitis (bubo).

Glandular fever and pulmonary artery thrombosis in a paraplegic patient, who had undergone splenectomy for splenic trauma sustained along with spinal cord injury: misdiagnosed initially as urine infection and later as lymphoma when CT scan revealed enlarged lymph nodes: a case report.

A 36-year-old male sustained fracture of first lumbar vertebra, splenic tear and paraplegia in a motorcycle accident in 2001; splenectomy was performed. In 2008, he presented with temperature and feeling rough. With a diagnosis of urine infection, he was prescribed ciprofloxacin, followed by trimethoprim, amoxicillin, and gentamicin, as temperature did not subside. White cell count was 21.2 x 109/L; lymphocytes were 13.05 x 109/L (1.00 - 4.00). Therefore, computerised tomography (CT) of chest and abdomen was performed. Thrombus was present in pulmonary arteries bilaterally involving the lobar and segmental branches. Enlarged lymph nodes were seen in axillae, chest, abdomen and inguinal regions. Radiological diagnosis was lymphoma. Cell marker showed an excess of large granular lymphocytes and activated lymphocytes. The Glandular Fever Slide Test was positive. Subsequently, Paul Bunnell test was also positive. Epstein Barr virus serology was consistent with recent Epstein Barr virus infection. Antibiotic was omitted; enoxaparin was prescribed for pulmonary artery thrombosis. Learning points from this case: (1) Although routine administration of antibiotic to a spinal cord injury patient with pyrexia may be acceptable in outpatient setting, other possibilities such as infection by multi-drug resistant organism, viral infection, venous or, arterial thrombosis should be considered if a patient does not respond promptly to antibacterial therapy. (2) When full blood count showed lymphocytosis (comprising > 50% of white blood cells) with atypical morphology, lymphocyte surface markers, Paul Bunnell test, and Epstein Barr virus serology should be performed. These tests would have led to a diagnosis of infectious mononucleosis, and abdominal imaging studies could have been avoided. (3) Lymphoid hyperplasia is the hallmark of infectious mononucleosis; therefore, we should have suspected glandular fever rather than lymphoma when CT scan revealed enlarged lymph nodes in abdomen, mediastinum, axillae and inguinal regions in this patient, who had lymphocytosis with atypical morphology. (4) A soft tissue mass, situated inferior to left hemidiaphragm in this asplenic patient, was misinterpreted as lymph nodes; review of CT led to the correct diagnosis of splenunculus. (5) Acute infection with Epstein Barr virus may lead to transient induction of anti-phospholipid antibodies, which can cause vascular thrombosis. (6) This case illustrates the value of reviewing test results and discussion with senior doctors, as these measures help to recognize medical errors and improve patient care.

Sexual health clinic

In a private room or space, the patient will partially undress. The clinician may inspect the patient's: Throat and lymph nodes of the neck for inflammation Pubic hair for lice Lymph nodes of the groin for swelling Genitals, anus, and surrounding areas for sores and warts The clinician may swab the patient's: Throat to test for gonorrhea and possibly chlamydia Cheek, inside, to diagnose HIV Sores of the genitals, anus, and surrounding areas to test for herpes Urethra to test for gonorrhea and possibly chlamydia Vagina to test for chlamydia and possibly gonorrhea Cervix to test for cervical intraepithelial neoplasia (a Pap test) Rectum to test for gonorrhea and possibly chlamydia The clinician may take small blood samples by pricking a finger or from a vein to test for HIV, syphilis, and possibly herpes and hepatitis C.

Infectious mononucleosis

Physical examination The presence of an enlarged spleen, and swollen posterior cervical, axillary, and inguinal lymph nodes are the most useful to suspect a diagnosis of infectious mononucleosis. On the other hand, the absence of swollen cervical lymph nodes and fatigue are the most useful to dismiss the idea of infectious mononucleosis as the correct diagnosis. The insensitivity of the physical examination in detecting an enlarged spleen means it should not be used as evidence against infectious mononucleosis. A physical examination may also show petechiae in the palate. Heterophile antibody test


Ivabradine, in fact, is contraindicated in patients with atrial fibrillation. Initially (although evidence has recently emerged that qualifies this information) ivabradine was said to be selective over the sodium If current in the sinus node. If the patient is in AF, it makes no sense to act on the sinus node.

An 84-year-old man with chronic heart failure in functional grade II secondary to ischemic heart disease with severe non-revascularizable systolic dysfunction, stage 3 chronic kidney disease (glomerular filtration rate 45-50 mL/min) and permanent atrial fibrillation with heart rate >80 beats per minute. Which of the following drugs does NOT provide benefit to the patient according to the currently available evidence?

Angiotensin converting enzyme inhibitors.

[Pharmacotherapy of chronic heart failure in clinical practice].

Chronic heart failure affects between 1-5% of the population and rise steeply with age. Most patients with chronic heart failure should be routinely managed with a combination of 4 types of drugs: a diuretic, an angiotensin converting enzyme inhibitors (ACE-I), beta-blocker and usually digitalis. Diuretics are essential for symptomatic treatment when fluid overload is present, and should always be administrated in combination with ACE-I if possible. ACE-I improves survival and symptoms and reduces hospitalization in patients with moderate to severe ventricular systolic dysfunction, and in the absence of fluid retention should be given first. Angiotensin II receptor antagonist could be considered in patients who not tolerate ACE-I. beta-blocking agents are recommended for treatment of patients with stable, mild, moderate and severe heart failure unless there is a contraindication. Bisoprolol, metoprolol and carvedilol have been associated with reduction in total mortality, cardiovascular mortality and sudden death. Cardiac glycosides are indicated in atrial fibrillation and any degree of symptomatic heart failure in order slow ventricular rate. Indications for antiarrhythmic drug therapy include atrial fibrillation, non-sustained or sustained ventricular tachycardia. Oral anticoagulation reduces the risk of stroke in patients with atrial fibrillation, and there is a lack of evidence to support the use of antithrombotic therapy in patients in sinus rhythm.

[Features of the treatment of heart failure in the elderly].

PHARMACOLOGICAL MODIFICATIONS TO BE TAKEN INTO ACCOUNT: In elderly patients, there is a modification in the distribution columns of drugs, an alteration in glomerular filtration (doses require adaptation) and tubular function (greater sensitivity to low salt diet and diuretics), and a reduction in the hepatic elimination capacity. FOR SYSTOLIC HEART FAILURE: The choice of drugs is in practice the same as that for younger patients: diuretics, antialdosterone agents, converting enzyme inhibitors, angiotensin II receptor antagonists, beta-blockers and digitalics. FOR DIASTOLIC HEART FAILURE: The therapeutic approach combines an etiologic treatment (blood pressure, myocardial ischaemia), prevention and the rapid treatment of the decompensation factors (atrial arrhythmia), a pharmacological treatment (converting enzyme inhibitors, angiotensin II receptor antagonists, and bradycardia lowering agents). Non-pharmacological measures include dietary restrictions, regular physical exercise, and education for the patient and the family.

Cardiovascular outcomes in high-risk hypertensive patients stratified by baseline glomerular filtration rate.

Chronic kidney disease is common in older patients with hypertension. To compare rates of coronary heart disease (CHD) and end-stage renal disease (ESRD) events; to determine whether glomerular filtration rate (GFR) independently predicts risk for CHD; and to report the efficacy of first-step treatment with a calcium-channel blocker (amlodipine) or an angiotensin-converting enzyme inhibitor (lisinopril), each compared with a diuretic (chlorthalidone), in modifying cardiovascular disease (CVD) outcomes in high-risk patients with hypertension stratified by GFR. Post hoc subgroup analysis. Multicenter randomized, double-blind, controlled trial. Persons with hypertension who were 55 years of age or older with 1 or more risk factors for CHD and who were stratified into 3 baseline GFR groups: normal or increased (> or = 90 mL/min per 1.73 m2; n = 8126 patients), mild reduction (60 to 89 mL/min per 1.73 m2; n = 18,109 patients), and moderate or severe reduction (< 60 mL/min per 1.73 m2; n = 5662 patients). Random assignment to chlorthalidone, amlodipine, or lisinopril. Rates of ESRD, CHD, stroke, and combined CVD (CHD, coronary revascularization, angina, stroke, heart failure, and peripheral arterial disease). In participants with a moderate to severe reduction in GFR, 6-year rates were higher for CHD than for ESRD (15.4% vs. 6.0%, respectively). A baseline GFR of less than 53 mL/min per 1.73 m2 (compared with >104 mL/min per 1.73 m2) was independently associated with a 32% higher risk for CHD. Amlodipine was similar to chlorthalidone in reducing CHD (16.0% vs. 15.2%, respectively; hazard ratio, 1.06 [95% CI, 0.89 to 1.27]), stroke, and combined CVD (CHD, coronary revascularization, angina, stroke, heart failure, and peripheral arterial disease), but less effective in preventing heart failure. Lisinopril was similar to chlorthalidone in preventing CHD (15.1% vs. 15.2%, respectively; hazard ratio, 1.00 [CI, 0.84 to 1.20]), but was less effective in reducing stroke, combined CVD events, and heart failure. Proteinuria data were not available, and combination therapies were not tested. Older high-risk patients with hypertension and reduced GFR are more likely to develop CHD than to develop ESRD. A low GFR independently predicts increased risk for CHD. Neither amlodipine nor lisinopril is superior to chlorthalidone in preventing CHD, stroke, or combined CVD, and chlorthalidone is superior to both for preventing heart failure, independent of level of renal function.

TIMI

TIMI Risk Score for STEMI Age 65-74 years? Yes (+2) – or – Age ≥75 years? Yes (+3) Diabetes, Hypertension or Angina? Yes (+1) Systolic BP < 100 mmHg? Yes (+3) Heart rate > 100? Yes (+2) Killip Class II-IV (JVD or any pulmonary exam findings of CHF)? Yes (+2) Weight < 67kg (147.7 lbs)? Yes (+1) Anterior ST Elevation or LBBB? Yes (+1) Time to treatment > 4 hours? Yes (+1) What Does This Score Mean? TIMI Risk Score for HF in Diabetes Prior heart failure? Yes (+2) History of atrial fibrillation? Yes (+1) Coronary artery disease? Yes (+1) eGFR < 60 ml/min/1.73*m2? Yes (+1) Urine albumin-to-creatinine ratio >300 mg/g? Yes (+2) – or – Urine albumin-to-creatinine ratio 30-300 mg/g? Yes (+1) What Does This Score Mean?

Pharmacotherapy for heart failure in patients with renal insufficiency.

Clinical trials have demonstrated that angiotensin-converting enzyme (ACE) inhibitors, beta-blockers, and spironolactone improve survival in patients with heart failure. Because patients with heart failure and renal insufficiency have been underrepresented in these trials, little evidence is available to guide clinicians in the optimal management of patients with both conditions. Approximately one third to one half of patients with heart failure have renal insufficiency (estimated glomerular filtration rate [GFR] <60 mL/min per 1.73 m2), and renal insufficiency is among the strongest predictors of mortality in patients with heart failure. Evidence supports the use of ACE inhibitors to improve survival in patients with moderate renal insufficiency (GFR, 30 to 60 mL/min per 1.73 m2), but there is little evidence with which to weigh the risks and benefits in patients with more advanced renal dysfunction. beta-Blockers improve survival in patients with heart failure, and their beneficial effect is unlikely to differ according to renal function. Spironolactone improves outcomes in patients with advanced heart failure, but renal insufficiency appears to increase risk for hyperkalemia and limits the use of the drug in patients with severe renal insufficiency. Future clinical trials in heart failure should include a representative number of patients with renal insufficiency to improve the evidence base and outcomes in this vulnerable population.

Angiotensin II receptor blocker

A 2016 meta-analysis including 148,334 patients found no significant differences in cancer incidence associated with ARB use. Kidney failure Although ARBs have protective effects against developing kidney diseases for patients with diabetes and previous hypertension without administration of ARBs, ARBs may worsen kidney functions such as reducing glomerular filtration rate associated with a rise of serum creatinine in patients with pre-existing proteinuria, renal artery stenosis, hypertensive nephrosclerosis, heart failure, polycystic kidney disease, chronic kidney disease, interstitial fibrosis, focal segmental glomerulosclerosis, or any conditions such as ARBs-treated but still clinically present hypertension that lead to abnormal narrowing of blood vessels to the kidney that interrupts oxygen and nutrient supply to the organ. History

Antihypertensive drug

The ratio of CCBs' anti-proteinuria effect, non-dihydropyridine to dihydropyridine was 30 to -2. ACE inhibitors ACE inhibitors inhibit the activity of angiotensin-converting enzyme (ACE), an enzyme responsible for the conversion of angiotensin I into angiotensin II, a potent vasoconstrictor. captopril enalapril fosinopril lisinopril moexipril perindopril quinapril ramipril trandolapril benazepril A systematic review of 63 trials with over 35,000 participants indicated ACE inhibitors significantly reduced doubling of serum creatinine levels compared to other drugs (ARBs, α blockers, β blockers, etc.), and the authors suggested this as a first line of defense. The AASK trial showed that ACE inhibitors are more effective at slowing down the decline of kidney function compared to calcium channel blockers and beta blockers. As such, ACE inhibitors should be the drug treatment of choice for patients with chronic kidney disease regardless of race or diabetic status.

Ivabradine

Chronic heart failure In the SHIFT study, ivabradine significantly reduced the risk of the primary composite endpoint of hospitalization for worsening heart failure or cardiovascular death by 18% (P<0.0001) compared with placebo on top of optimal therapy. These benefits were observed after 3 months of treatment. SHIFT also showed that administration of ivabradine to heart failure patients significantly reduced the risk of death from heart failure by 26% (P=0.014) and hospitalization for heart failure by 26% (P<0.0001). The improvements in outcomes were observed throughout all prespecified subgroups: female and male, with or without beta-blockers at randomization, patients below and over 65 years of age, with heart failure of ischemic or non-ischemic etiology, NYHA class II or class III, IV, with or without diabetes, and with or without hypertension.

Atrial fibrillation

Rate control Rate control to a target heart rate of fewer than 110 beats per minute is recommended in most people. Lower heart rates may be recommended in those with left ventricular hypertrophy or reduced left ventricular function. Rate control is achieved with medications that work by increasing the degree of the block at the level of the AV node, decreasing the number of impulses that conduct into the ventricles. This can be done with: Beta blockers (preferably the "cardioselective" beta blockers such as metoprolol, bisoprolol, or nebivolol) Non-dihydropyridine calcium channel blockers (e.g., diltiazem or verapamil) Cardiac glycosides (e.g., digoxin) – have less use, apart from in older people who are sedentary. They are not as effective as either beta-blockers or calcium channel blockers. In those with chronic AF either beta blockers or calcium channel blockers are recommended.

Ivabradine

Medical uses It is used for the symptomatic treatment of chronic stable angina pectoris in patients with normal sinus rhythm who cannot take beta blockers. It is also being used off-label in the treatment of inappropriate sinus tachycardia.Ivabradine stands as a pharmacological option for controlling HR and rhythm without associated side effects in postoperative CABG patients with IST Chest pain It may be as effective as the beta blocker atenolol and comparable with amlodipine in the management of chronic stable angina. Heart failure It is used in combination with beta blockers in people with heart failure with LVEF lower than 35 percent inadequately controlled by beta blockers alone and whose heart rate exceeds 70 beats per minute. In people not sufficiently managed with beta blockers for their heart failure adding ivabradine decreases the risk of hospitalization for heart failure.

Antihypertensive drug

Chronic kidney disease. ACE inhibitors or ARBs should be included in the treatment plan to improve kidney outcomes regardless of race or diabetic status. Late-stage Dementia should consider Deprescribing antihypertensives, according to the Medication Appropriateness Tool for Comorbid Health Conditions in Dementia (MATCH-D) Diabetes mellitus. The ACE inhibitors and angiotensin receptor blockers have been shown to prevent the kidney and retinal complications of diabetes mellitus. Gout may be worsened by thiazide diuretics, while losartan reduces serum urate. Kidney stones may be improved with the use of thiazide-type diuretics Heart block. β-blockers and nondihydropyridine calcium channel blockers should not be used in patients with heart block greater than first degree. JNC8 does not recommend β-blockers as initial therapy for hypertension

Glomerular filtration rate

The severity of chronic kidney disease (CKD) is described by six stages; the most severe three are defined by the MDRD-eGFR value, and first three also depend on whether there is other evidence of kidney disease (e.g., proteinuria): 0) Normal kidney function – GFR above 90 mL/min/1.73 m2 and no proteinuria 1) CKD1 – GFR above 90 mL/min/1.73 m2 with evidence of kidney damage 2) CKD2 (mild) – GFR of 60 to 89 mL/min/1.73 m2 with evidence of kidney damage 3) CKD3 (moderate) – GFR of 30 to 59 mL/min/1.73 m2 4) CKD4 (severe) – GFR of 15 to 29 mL/min/1.73 m2 5) CKD5 kidney failure – GFR less than 15 mL/min/1.73 m2 Some people add CKD5D for those stage 5 patients requiring dialysis; many patients in CKD5 are not yet on dialysis. Note: others add a "T" to patients who have had a transplant regardless of stage.

[Cardiovascular Medication in Elderly Patients].

Elderly people show increased probability to develop atherosclerotic diseases; in consequence heart failure - most often following coronary heart disease - as well as atrial fibrillation is more common. Following guidelines may lead to polypharmacy, i. e. use of more than 5 drugs daily. Thus, drug interactions as well as side effects become more likely; especially in elderly patients reduced kidney function has to be taken into account. Only drugs which have shown to prolong life or to reduce symptoms in controlled clinical trials should be used. There is little evidence to use low dose aspirin or lipid lowering agents in primary prevention especially in elderly. ACE inhibitors, β blocker and MRA are effective to improve symptoms and outcome in HFrEF but not in HFmEF or HFpEF. This also holds true for the elderly. Withdrawal of long term diuretic treatment in the elderly patients may lead to symptoms of heart failure or increase in blood pressure to hypertensive values often. In coronary heart disease ß blocker may be used to control symptoms as well as to reduce the need for coronary intervention following 1 year after myocardial infarction. Because the risk of stroke increases with age more than the risk of bleeding, the absolute benefit of oral anticoagulation in atrial fibrillation patients is highest in the elderly. NOAK appear to be safer and at least as efficacious as warfarin.

Heart failure

Beta-adrenergic blocking agents (beta blockers) also form part of the first line of treatment, adding to the improvement in symptoms and mortality provided by ACE-I/ARB. The mortality benefits of beta blockers in people with systolic dysfunction who also have atrial fibrillation is more limited than in those who do not have it. If the ejection fraction is not diminished (HFpEF), the benefits of beta blockers are more modest; a decrease in mortality has been observed, but reduction in hospital admission for uncontrolled symptoms has not been observed. In people who are intolerant of ACE-I and ARBs or who have significant kidney dysfunction, the use of combined hydralazine and a long-acting nitrate, such as isosorbide dinitrate, is an effective alternate strategy. This regimen has been shown to reduce mortality in people with moderate heart failure. It is especially beneficial in the black population.

Renin-angiotensin inhibition in systolic heart failure and chronic kidney disease.

The role of renin-angiotensin inhibition in older patients with systolic heart failure with chronic kidney disease remains unclear. Of the 1665 patients (aged≥65 years) with systolic heart failure (ejection fraction<45%) and chronic kidney disease (estimated glomerular filtration rate<60 mL/min/1.73 m(2)), 1046 received angiotensin-converting enzyme inhibitors or angiotensin receptor blockers. Propensity scores for the receipt of these drugs, estimated for each of the 1665 patients, were used to assemble a matched cohort of 444 pairs of patients receiving and not receiving these drugs who were balanced on 56 baseline characteristics. During more than 8 years of follow-up, all-cause mortality occurred in 75% and 79% of matched patients with chronic kidney disease receiving and not receiving angiotensin-converting enzyme inhibitors or angiotensin receptor blockers, respectively (hazard ratio [HR], 0.86; 95% confidence interval [CI], 0.74-0.996; P=.045). There was no significant association with heart failure hospitalization (HR, 0.86; 95% CI, 0.72-1.03; P=.094). Similar mortality reduction (HR, 0.83; 95% CI, 0.70-1.00; P=.046) occurred in a subgroup of matched patients with estimated glomerular filtration rate less than 45 mL/min/1.73 m(2). Among 171 pairs of propensity-matched patients without chronic kidney disease, the use of these drugs was associated with a significant reduction in all-cause mortality (HR, 0.72; 95% CI, 0.55-0.94; P=.015) and heart failure hospitalization (HR, 0.71; 95% CI, 0.52-0.95; P=.023). Discharge prescription of angiotensin-converting enzyme inhibitors or angiotensin receptor blockers was associated with a significant modest reduction in all-cause mortality in older patients with systolic heart failure with chronic kidney disease, including those with more advanced chronic kidney disease.

[The use of beta blockers in heart failure: clinical studies].

Although inhibitors of angiotensin-converting enzyme (ACE) have improved the treatment of chronic heart failure (CHF), mortality related to this disorder remains unacceptably high. Results from studies started more than 25 years ago in Sweden suggested that long-term therapy with beta-blockers could improve hemodynamics and increase survival in patients with CHF; this hypothesis is confirmed by the results of six double-blind, randomized, placebo-controlled trials (MDC, CIBIS, ANZ, US Carvedilol Study, CIBIS II and MERIT-HF) who enrolled about 9000 patients with CHF. In these trials beta-blockers (metoprolol, bisoprolol or carvedilol) where added to the stable usual treatment of each patient (ACE-inhibitors, diuretics, digoxin). Baseline characteristics of patients enrolled into the beta-blocker or placebo arm were similar in all these studies. Specifically the mean patient's age was < 60 years, with a mean left ventricular ejection fraction of 25-26%, 30% of enrolled patients were in NYHA functional class II and 60% in NYHA functional class III, CHF was due to ischemic heart disease in about 60% of patients. The average follow-up for all the trials was 14.5 +/- 5.6 months. On the whole in patients on beta-blocker treatment there is a 33.3% reduction in total mortality rate, a 34.2% reduction in cardiac death rate, a 37.7% reduction in sudden death rate, and a 41.7% reduction in worsening heart failure mortality rate. Moreover, in beta-blocker patients there is a 31.7% reduction in all-cause readmissions to hospital and a 26% reduction in the combined end point (total mortality and hospital readmission). Beta-blockers improved ventricular function but there was no significant improvement in functional capacity. In conclusion, the results of the six trials considered indicate that there is convincing evidence supporting a favorable effect of beta-blockade on the risk of death and readmission to hospital in patients with dilated cardiomyopathy with systolic dysfunction, aged < 70 years, in NYHA functional class II-III. The effects of these drugs in CHF patients a) with normal left ventricular ejection fraction, b) aged > 65-70 years, c) in NYHA functional class IV, and d) with comorbilities such as obstructive lung disease, diabetes, peripheral arterial diseases, require additional study.

Digitalis

under current regulations by the Food and Drug Administration on the basis of prospective, randomized study and clinical trials. It was also approved for the control of ventricular response rate for patients with atrial fibrillation. American College of Cardiology/American Heart Association guidelines recommend digoxin for symptomatic chronic heart failure for patients with reduced systolic function, preservation of systolic function, and/or rate control for atrial fibrillation with a rapid ventricular response. Heart Failure Society of America guidelines for heart failure provide similar recommendations. Despite its relatively recent approval by the Food and Drug Administration and the guideline recommendations, the therapeutic use of digoxin is declining in patients with heart failure—likely the result of several factors. The main factor is the more recent introduction of several drugs shown in randomised controlled studies to improve outcomes in heart failure. Safety concerns

Renal implications of the renin-angiotensin-aldosterone system blockade in heart failure.

The renin-angiotensin-aldosterone system actively participates in the derangement of renal function since the early stages of heart failure (HF). A diminished capacity to excrete sodium secondary to increased proximal tubular re-absorption and loss of the renal functional reserve are the two most relevant initial alterations of renal function in which angiotensin II has been proven to act directly. Meanwhile, the octapeptide contributes to maintain glomerular filtration rate (GFR) within normal limits through efferent arteriole vasoconstriction. Administration of angiotensin converting enzyme inhibitors (ACEi) or angiotensin receptor antagonists (ARA) may thus be accompanied by a functional fall in that parameter. Advanced age, higher initial serum creatinine, history of hypertension, diabetes and atrial fibrillation predict the onset of GFR impairment associated with blockade of the renin-angiotensin system. Concomitant administration of betablockers may help to protect renal function, and preliminary data indicate that the combination of ACEi and ARA is not accompanied by a higher renal risk. The good prognostic effects of aldosterone antagonists in HF does not seem to be related to intrarenal effects of these compounds with the exception of preventing potassium loss and hypokalemia. The systematic therapeutic use of drug(s) provided with beneficial renal effects, to treat arterial hypertension or myocardial ischemia, may contribute to delay of, or prevent the development of HF.

Protection: risk ratio of antihypertensive drug treatment in the elderly.

In recent controlled trials using clinic-based manometry, thiazides and beta-blockers prevented cerebrovascular and coronary deaths in patients aged 60-79 years with cryptogenic hypertension (diastolic 90-119 mm Hg). Elderly patients should usually take low-dose thiazide with potassium replacement. beta-Blockers also postpone death, but may mask hypoglycaemia. Calcium blockers and low-dose angiotensin-converting enzyme (ACE) inhibitors appear preferable in diabetes, and thiazides or ACE inhibitors in heart failure or peripheral vascular disease. Maintaining average diastolic pressure at 80-84 mm Hg impairs function of the kidneys, and possibly the myocardium. Metabolic reactions worsen with age. Drug treatment should match individual daily function. By clinic manometry, the protection:risk ratio of antihypertensive treatment progressively decreases with age, reaching less than 1.0 in patients over 80-85 years. Twenty-four-hour ambulatory blood pressure information should guide treatment more reliably in patients greater than or equal to 60 years.

Heart failure

Treatment depends on the severity and cause of the disease. In people with chronic stable mild heart failure, treatment commonly consists of lifestyle modifications such as stopping smoking, physical exercise, and dietary changes, as well as medications. In those with heart failure due to left ventricular dysfunction, angiotensin converting enzyme inhibitors, angiotensin receptor blockers, or valsartan/sacubitril along with beta blockers are recommended. For those with severe disease, aldosterone antagonists, or hydralazine with a nitrate may be used. Diuretics are useful for preventing fluid retention and the resulting shortness of breath. Sometimes, depending on the cause, an implanted device such as a pacemaker or an implantable cardiac defibrillator may be recommended. In some moderate or severe cases, cardiac resynchronization therapy (CRT) or cardiac contractility modulation may be of benefit. A ventricular assist device (for the left, right, or both ventricles), or

Beta-blocker therapy in elderly patients with renal dysfunction and heart failure.

To assess the role of beta-blockers (BB) in patients with chronic kidney disease (CKD) aged ≥ 75 years. From January 2008 to July 2014, we included 390 consecutive patients ≥ 75 years of age with ejection fraction ≤ 35% and glomerular filtration rate (GFR) ≤ 60 mL/min per 1.73 m<sup2</sup. We analyzed the relationship between treatment with BB and mortality or cardiovascular events. The mean age of our population was 82.6 ± 4.1 years. Mean ejection fraction was 27.9% ± 6.5%. GFR was 60-45 mL/min per 1.73 m<sup2</sup in 50.3% of patients, 45-30 mL/min per 1.73 m<sup2</sup in 37.4%, and < 30 mL/min per 1.73 m <sup2</sup in 12.3%. At the conclusion of follow-up, 67.4% of patients were receiving BB. The median follow-up was 28.04 (IR: 19.41-36.67) months. During the study period, 211 patients (54.1%) died and 257 (65.9%) had a major cardiovascular event (death or hospitalization for heart failure). BB use was significantly associated with a reduced risk of death (HR = 0.51, 95% CI: 0.35-0.74;<iP</i < 0.001). Patients receiving BB consistently showed a reduced risk of death across the different stages of CKD: stage IIIa (GFR = 30-45 mL/min per 1.73 m <sup2</sup; HR = 0.47, 95% CI: 0.26-0.86,<iP</i < 0.0001), stage IIIb (GFR 30-45 mL/min per 1.73 m <sup2</sup; HR = 0.55, 95% CI: 0.26-1.06,<iP</i = 0.007), and stages IV and V (GFR < 30 mL/min per 1.73 m <sup2</sup; HR = 0.29, 95% CI: 0.11-0.76;<iP</i = 0.047). The use of BB in elderly patients with HFrEF and renal impairment was associated with a better prognosis. Use of BB should be encouraged when possible.

Renin-angiotensin inhibition in diastolic heart failure and chronic kidney disease.

The role of renin-angiotensin inhibition in older patients with diastolic heart failure and chronic kidney disease remains unclear. Of the 1340 patients (age ≥65 years) with diastolic heart failure (ejection fraction ≥45%) and chronic kidney disease (estimated glomerular filtration rate <60 mL/min/1.73 m(2)), 717 received angiotensin-converting enzyme inhibitors or angiotensin receptor blockers. Propensity scores for the use of these drugs, estimated for each of the 1340 patients, were used to assemble a cohort of 421 pairs of patients, receiving and not receiving these drugs, who were balanced on 56 baseline characteristics. During more than 8 years of follow-up, all-cause mortality occurred in 63% and 69% of matched patients with chronic kidney disease receiving and not receiving angiotensin-converting enzyme inhibitors or angiotensin receptor blockers, respectively (hazard ratio [HR], 0.82; 95% confidence interval [CI], 0.70-0.97; P = .021). There was no association with heart failure hospitalization (HR, 0.98; 95% CI, 0.82-1.18; P = .816). Similar mortality reduction (HR, 0.81; 95% CI, 0.66-0.995; P = .045) occurred in a subgroup of matched patients with an estimated glomerular filtration rate less than 45 mL/min/1.73 m(2). Among 207 pairs of propensity-matched patients without chronic kidney disease, the use of these drugs was not associated with mortality (HR, 1.03; 95% CI, 0.80-1.33; P = .826) or heart failure hospitalization (HR, 0.99; 95% CI, 0.76-1.30; P = .946). A discharge prescription for angiotensin-converting enzyme inhibitors or angiotensin receptor blockers was associated with a significant reduction in all-cause mortality in older patients with diastolic heart failure and chronic kidney disease, including those with more advanced chronic kidney disease.

Already low drug dose antagonism of the renin-angiotensin aldosterone system decreases 1-year mortality and rehospitalization in old heart failure patients.

Hospitalization for heart failure treatment (HHF) is an incisive event in the course of HF. Today, the large majority of HHF patients is ≥ 65 years and discharge HF drugs are most often not applied at dose levels acknowledged to provide prognostic benefit. This study therefore aims to investigate the treatment effect size of discharge HF drugs in old HHF patients. Drugs are analyzed according to pharmacological class. Individual discharge HF drug dose is reported as percentage of guidelines-recommended target dose. Primary endpoint was 1-year all-cause mortality (ACM) after discharge; the secondary endpoint combined 1-year ACM and first cardiovascular hospitalization within 1 year after discharge. Comparison between 65-80 years and > 80 years old study participants tested the relative treatment effect size as a function of respective age group. The 875 consecutive HHF patients had a median age of 82 years [76-87 years]; 48.6 % were females. Betablocker and diuretic treatment did not change the incidence of endpoints. Inhibition of the renin-angiotensin system (RASi), when compared to no treatment, decreased the incidence of endpoints both at the 1-25 % and the > 25 % target dose level. Antagonists of the mineralocorticoid receptor (MRA), when compared to no treatment, decreased the secondary endpoint at the 1-25 % target dose level but not at the > 25 % target dose level. The relative treatment effect size of RASi or MRA corresponded between the age strata for both endpoints. Low-dose RASi and MRA had beneficial effects in these old HHF patients.

Characteristics of clinical drugs for elderly chronic heart failure complicated with different degrees of renal insufficiency.

To investigate the characteristics of clinical therapeutic drugs in elderly chronic heart failure (CHF) patients complicated with different degrees of renal insufficiency. The elderly patients who were hospitalized from October 2010 to October 2015 in our hospital due to CHF for the first time were selected by means of retrospective case collection. The glomerular filtration rate was estimated by using the Modification of Diet in Renal Disease (MDRD) Study equation. The patients were divided into a group with normal renal function, a group with slight decrease in renal function, and a group with moderate and severe decrease in renal function. Statistical analysis was made to compare the characteristics of clinical drugs for the three groups. Compared with the normal renal function group and the slight decrease group, ACEIs and β-blockers were less used in the moderate and severe decrease group, but diuretics and spironolactone were more used (P<0.05). Compared with the normal renal function group, the use rate of ACEIs was low whereas that of diuretics was high (P<0.05). ACEIs and β-blockers were barely employed to treat elderly CHF patients complicated with renal insufficiency, but diuretics and spironolactone were frequently utilized.

The management of heart failure--an overview.

National and international societies have issued guidelines on the management of heart failure: The European Society of Cardiology, WHO, ACC/AHA Task Force Report, US Department of Health and Human Services, German Society of Cardiology. The therapeutic approaches to heart failure have undergone considerable changes during the last few years. The guidelines have to be updated almost yearly due to new results from prospective randomized studies. Although an agreement could be reached with respect to general measures and drug treatment, no agreement on mechanical devices, pacemakers and surgical interventions has been reached. The basis for medical treatment of chronic heart failure depends on diuretics, digitalis, ACE inhibitors, and beta-blockers. Calcium antagonists and other positive inotropic drugs, other than digitalis, should be avoided as far as possible. Thiazides, loop diuretics and aldosterone antagonists are needed for acute and chronic treatment of heart failure, alone or in combination (diuretic resistant heart failure!). Digitalis glycosides are needed in patients with atrial fibrillation with a fast ventricular rate or atrial flutter and in patients with systolic dysfunction, large hearts and symptomatic failure class NYHA III and IV. However, digitalis does not convert atrial fibrillation to sinus rhythm. Today there is no question that ACE inhibitors improve the prognosis of all patients with heart failure in all stages, if ejection fraction is reduced. Therefore, most patients after myocardial infarction or after having experienced pump failure due to myocarditis or cardiomyopathy are treated with ACE inhibitors and diuretics. The beneficial effects of ACE inhibitors seem to be most pronounced the worse the situation is. Relative risk reductions (mortality!) between 10% and 40% have been published depending on the severity of symptomatic left ventricular dysfunction. Those patients with high absolute risk have more to gain than those with low risk for any given "risk reduction", of course. Recent studies also indicate that most high risk cardiac patients profit from ACE inhibitors even if pump function is normal (i.e., patients with coronary heart disease, diabetes mellitus, cerebral vascular disease, hypertension) (15). AT1 antagonists can substitute for ACE inhibitors, if the latter are not tolerated due to cough. Up to now, beta-blocking agents apart from diuretics seem to be the best investigated drugs in heart failure. Large controlled studies with bisoprolol, carvedilol and metoprolol in addition to diuretics, digitalis and ACE inhibitors convincingly yielded positive results in chronic left ventricular failure patients. Reduction of mortality by 35% and even of sudden cardiac deaths by 40% have been proven beyond doubt. Thus, heart failure patients today should also receive beta-blocking agents in all stages of the disease. In the era of controlled prospective studies (evidence-based medicine), physicians are well advised to use only drugs that have been proven beneficial in large controlled studies.

Cardiovascular medication in relation to renal function after coronary artery bypass surgery.

Guidelines for recommended medication use for the secondary prevention of coronary heart disease are exceedingly important in patients with chronic kidney disease. Despite a high risk for recurrent cardiovascular events, these patients are less likely to use evidence-based recommended medications. The objective of the current study was to analyze the association between renal function and guideline-recommended drug therapy in patients with coronary heart disease. In this nationwide population-based cohort study, we included 12,332 patients with established coronary heart disease who underwent primary isolated coronary artery bypass grafting in Sweden between 2005 and 2008. Medication use was retrieved from the national Prescribed Drug Register. During the first year after coronary surgery, 94% of patients had at least two dispensed prescriptions for an antiplatelet agent, 68% for an angiotensin-converting enzyme inhibitor or angiotensin II receptor blocker, 92% for a beta-blocker, and 93% for a statin. Only 57% of all patients had prescriptions for all four medication classes. Reduced renal function (estimated glomerular filtration rate (eGFR) of 30 to 45 mL/min per 1.73 m(2) and <30 mL/min per 1.73 m(2)) was significantly associated with a lower use of all four medication classes (adjusted risk ratio 0.89, 95% confidence interval 0.82 to 0.98; and adjusted risk ratio 0.75, 95% confidence interval 0.62 to 0.90, respectively) as compared to normal renal function (eGFR >60 mL/min per 1.73 m(2)). In patients with established coronary heart disease, moderate to severe renal dysfunction was associated with significantly lower use of guideline-recommend medications as compared to normal renal function.

Antihypertensive Medication Use in Older Patients Transitioning from Chronic Kidney Disease to End-Stage Renal Disease on Dialysis.

The transition from CKD to ESRD can be particularly unstable, with high rates of death and hospitalizations. Few studies have examined medication use during this critical period. We examined patterns of antihypertensive medication use from the four quarters before and eight quarters after incident ESRD treated with maintenance dialysis. We used the US Renal Data System to identify patients aged ≥67 years initiating dialysis for ESRD between January 2008 and December 2010 with Medicare Part D and a low-income subsidy. We ascertained the incidence of AKI and hyperkalemia during each quarter on the basis of having at least 1 payment claim for the condition. We used Poisson regression with robust SEMs to formally test for changes in the trend and level of antihypertensive medication use in a series of intervention analyses. The number of antihypertensive drugs used increased as patients neared ESRD, peaking at an average of 3.4 in the quarter immediately preceding dialysis initiation, then declining to 2.2 medications by 2 years later. Angiotensin-converting enzyme inhibitor/angiotensin II receptor blocker use was stable at approximately 40%, even among patients with coronary disease and systolic heart failure, and did not correlate with AKI or hyperkalemia. Dialysis initiation was associated with a 40% (95% confidence interval, 38% to 43%) lower adjusted level of diuretic use, which continued to decline after ESRD. Three- and four-drug combinations that included a diuretic were most common before ESRD, whereas after ESRD, one- and two-drug β-blocker or calcium-channel blocker-based combinations were most common. The use of antihypertensive medications, particularly angiotensin-converting enzyme inhibitor/angiotensin II receptor blockers and diuretics, may be suboptimal during the transition from CKD to ESRD, especially in patients with coronary disease or systolic heart failure. Future studies are needed to identify strategies to increase the appropriate use of antihypertensive medications during this critical transition period.

Heart failure with preserved ejection fraction

Beta-blockers are the first-line therapy: they lower the heart rate and thus give more time for ventricles to fill. They may also improve survival. There is some evidence that calcium channel blockers may be of benefit in reducing ventricular stiffness. In some cases, (verapamil has the benefit lowering the heart rate). Angiotensin converting enzyme (ACE) inhibitors Likewise, treatment with angiotensin converting enzyme inhibitors, such as enalapril, ramipril, and many others, may be of benefit due to their effect on preventing ventricular remodeling but under control to avoid hypotension. ACE inhibitors do not appear to improve morbidity or mortality associated with HFpEF alone. However, they are important in the management of hypertension, a significant player in the pathophysiology of HFpEF. Angiotensin II receptor blockers (ARBs) ARB treatment results in an improvement in diastolic dysfunction and hypertension that is comparable to other anti-hypertensive medication.

[What can be achieved by treatment with antihypertensive agents? Report from a hearing].

Today it is considered a primary goal to reduce morbidity and mortality from stroke. It will probably also be possible to reduce other pressure-related illnesses, such as heart failure and renal failure. Coronary morbidity is influenced to some extent only, and involves risk of over-treatment. There is most probably a J-shaped relationship between achieved reduction of pressure and mortality. Treatment with drugs is considered when diastolic pressures exceed 90 mm Hg, provided that the patient has been observed when treated in other ways than by drugs for several months. If no other risk factors are present, 5-10 mm Hg higher diastolic blood pressure levels can be accepted. However, all patients with diastolic pressure above 100 mm Hg should be treated. In patients with coronary disease it is advisable not to lower diastolic blood pressure below 85 mm Hg. One should hesitate to give antihypertensive drugs to individuals with high pressures at the doctor's and normal pressures at home. They should preferably receive intense non-drug treatment aimed at reducing total cardiovascular risk.

Candesartan

Prevention of atrial fibrillation Results from a meta-analysis completed in 2005 demonstrated a reduction in atrial fibrillation in patients with systolic left ventricular dysfunction treated with candesartan, another angiotensin receptor blocker or an angiotensin converting enzyme inhibitor. Evidence for the use of candesartan specifically is also supported by an analysis of the CHARM study which demonstrated a reduction in atrial fibrillation in patients with systolic left ventricular dysfunction. While these studies have demonstrated a potential additional benefit for candesartan when used in patients with systolic left ventricular dysfunction, additional studies are required to further elucidate the role of candesartan in the prevention of atrial fibrillation in other population groups.

[Association between duration of digoxin use and adverse outcomes among Chinese patients with atrial fibrillation].

<bObjective:</b We aimed to explore the impact of digoxin use on outcomes in Chinese patients with atrial fibrillation (AF). <bMethods:</b We used the dataset from the Chinese Atrial Fibrillation Registry, a prospective, multicenter, hospital-based registry study. According to the inclusion and exclusion criteria, 10 472 eligible patients enrolled from August 2011 to December 2016 were included in this ancillary study. The patients were classified into three groups according to the status of digoxin use at study enrollment, patients already receiving digoxin before registry were represented as continuous group, patients initiated on digoxin for the first time were represented as newly group, and patients without digoxin prescription at enrollment were represented as control group. Patients were followed by telephone or outpatient service every 6 months. Kaplan-Meier survival analysis and Cox proportional hazards regression models were used to investigate the association of digoxin use with adverse outcomes (all-cause death, cardiovascular death and cardiovascular hospitalization). <bResults:</b In the overall study population, men accounted for 42.8%, and the average age was (66.9±11.8) years. There were 777（7.42%）patients in continuous group, 375 (3.58%) patients in newly group, and 9 320 (89.00%) patients in control group. Compared with the control group, the patients in the newly group and the continuous group were older, had faster heart rate, lower estimated glomerular filtration rate, higher proportion of persistent atrial fibrillation, heart failure, renal insufficiency, diabetes mellitus, ischemic stroke, coronary heart disease, vascular disease and bleeding history. At the same time, the patients in the newly group and the continuous group were treated more often with anticoagulants, antiplatelet drugs, ACE inhibitors or angiotensin receptor blockers, beta-receptor blockers while the proportion of antiarrhythmic drugs was lower as compared to control group (<iP</i<0.05). During a median follow-up of 36 months (interquartile range: 18-48 month), risk of all-cause mortality was significantly higher in newly group compared to control group (7.3% vs. 4.7%, <iP</i<0.05), the rates of all-cause mortality, cardiovascular death and cardiovascular hospitalization were all higher in continuous group than in control group (8.0% vs. 4.7%; 4.7% vs. 3.0%; 16.7% vs<i.</i 11.8%; <iP</i all<0.05). After adjustment for age, male, body mass index, blood pressure, heart rate, renal function, AF type, history of stroke, heart failure, diabetes, coronary artery disease and other drugs treatment, the association between newly group and adverse outcomes was not significant, however, digoxin use was associated with increased all-cause mortality (<iHR</i 1.26; 95%<iCI</i 1.04-1.56; <iP</i=0.019), cardiovascular death (<iHR</i 1.38; 95%<iCI</i 1.08-1.77, <iP</i =0.01), and cardiovascular hospitalization (<iHR</i 1.10; 95%<iCI</i 1.06-1.52, <iP</i=0.02) in continuous group. <bConclusion:</b Continuous digoxin use is associated with a significant increase in adverse outcomes among Chinese patients with atrial fibrillation.

Current drug treatment and treatment patterns with antihypertensive drugs.

The 4 major classes of antihypertensive drugs are diuretics, beta-blockers, ACE inhibitors and calcium antagonists. The diuretics have recently regained prominence, largely due to the results of recent controlled trials. These trials in elderly patients demonstrated that low-dose diuretics were effective not only in preventing stroke but also in greatly reducing coronary-related events. Diuretics also decrease left ventricular mass more than the other major drug classes. In addition, they are the most effective drugs for use in combination therapy. By contrast, the safety of calcium antagonists has recently been questioned because of report of increased coronary morbidity and mortality. However, these adverse events may be restricted to the short-acting preparations, especially nifedipine, which causes cardiac stimulation. ACE inhibitors, like beta-blockers, are not only effective in reducing blood pressure, particularly when combined with a diuretic, but also improve angina and decrease postinfarction mortality. They also benefit congestive heart failure, stabilise or improve renal function in hypertensive and diabetic nephropathy and reduce albuminuria. Beta-Blockers are especially effective in reducing sudden cardiac death in patients with coronary heart disease, particularly in postinfarction patients. Final proof of the relative effectiveness of these drugs in preventing morbidity and mortality must await the outcome of large comparative trials currently under way. A recent national survey in the US found that more than 75% of hypertensive patients did not have their hypertension completely controlled. Possible reasons for this disturbing statistic are discussed along with suggestions for improvement.