Signs and symptoms of<unk> <unk> coid affecting the skin<unk>  is a systemic inflammatory disease that can affect any organ, although it can be asymptomatic and is discovered by accident in about 5% of cases. Common symptoms, which tend to be vague, include fatigue (unrelieved by sleep; occurs in up to 85% of cases ), lack of energy, weight loss, joint aches and pains (which occur in about 70% of cases), arthritis (14–38% of cases), dry eyes, swelling of the knees, blurry vision, shortness of breath, a dry, hacking cough, or skin lesions. Less commonly, people may cough up blood.<unk>  is also accompanied by psychological distress and symptoms of anxiety and depression, which are also associated with fatigue. The cutaneous symptoms vary, and range from rashes and noduli (small bumps) to erythema nodosum, granuloma annulare, or lupus pernio.<unk>  and cancer may mimic one another, making the distinction difficult. The combination of erythema nodosum, bilateral hilar lymphadenopathy, and joint pain is called Löfgren syndrome, which has a relatively good prognosis. This form of the disease occurs significantly more often in Scandinavian patients than in those of non-Scandinavian origin. Respiratory tract Localization to the lungs is by far the most common manifestation of<unk> . At least 90% of those affected experience lung involvement. Overall, about 50% develop permanent pulmonary abnormalities, and 5 to 15% have progressive fibrosis of the lung parenchyma.<unk>  of the lung is primarily an interstitial lung disease in which the inflammatory process involves the alveoli, small bronchi, and small blood vessels. In acute and subacute cases, physical examination usually reveals dry crackles. At least 5% of cases include pulmonary arterial hypertension. The upper respiratory tract (including the larynx, pharynx, and sinuses) may be affected, which occurs in between 5 and 10% of cases. The four stages of pulmonary involvement are based on radiological stage of the disease, which is helpful in prognosis: * Stage I: bilateral hilar lymphadenopathy (BHL) alone * Stage II: BHL with pulmonary infiltrates * Stage III: pulmonary infiltrates without BHL * Stage IV: fibrosis Use of the Scadding scale only provides general information regarding the prognosis of the pulmonary disease over time. Caution is recommended, as it only shows a general relation with physiological markers of the disease and the variation is such that it has limited applicability in individual assessments, including treatment decisions. Skin<unk>  involves the skin in between 9 and 37% of cases and is more common in African Americans than in European Americans. The skin is the second-most commonly affected organ after the lungs. The most common lesions are erythema nodosum, plaques, maculopapular eruptions, subcutaneous nodules, and lupus pernio. Treatment is not required, since the lesions usually resolve spontaneously in 2–4 weeks. Although it may be disfiguring, cutaneous<unk>  rarely causes major problems.<unk>  of the scalp presents with diffuse or patchy hair loss. Heart Histologically,<unk>  of the heart is an active granulomatous inflammation surrounded by reactive oedema. The distribution of affected areas is patchy with localised enlargement of heart muscles. This causes scarring and remodelling of the heart, which leads to dilatation of heart cavities and thinning of heart muscles. As the situation progresses, it leads to aneurysm of heart chambers. When the distribution is diffuse, there would be dilatation of both ventricles of the heart, causing heart failure and arrhythmia. When the conduction system in the intraventricular septum is affected, it would lead to heart block, ventricular tachycardia and ventricular arrhythmia, causing sudden death. Nevertheless, the involvement of pericardium and heart valves are uncommon. The frequency of cardiac involvement varies and is significantly influenced by race; in Japan, more than 25% of those with<unk>  have symptomatic cardiac involvement, whereas in the US and Europe, only about 5% of cases present with cardiac involvement. Autopsy studies in the US have revealed a frequency of cardiac involvement of about 20–30%, whereas autopsy studies in Japan have shown a frequency of 60%. The presentation of cardiac<unk>  can range from asymptomatic conduction abnormalities to fatal ventricular arrhythmia. Conduction abnormalities are the most common cardiac manifestations of<unk>  in humans and can include complete heart block. Second to conduction abnormalities, in frequency, are ventricular arrhythmias, which occurs in about 23% of cases with cardiac involvement. Sudden cardiac death, either due to ventricular arrhythmias or complete heart block is a rare complication of cardiac<unk> . Cardiac<unk>  can cause fibrosis, granuloma formation, or the accumulation of fluid in the interstitium of the heart, or a combination of the former two. Cardiac<unk>  may also cause congestive heart failure when granulomas cause myocardial fibrosis and scarring. Congestive heart failure affects 25-75% of those with cardiac<unk> . Diabetes mellitus and<unk> -related arrhythmias are believed to be strong risk factors of heart failure in<unk> . A small (20-40%) increased risk of acute myocardial infarction has also been described. Pulmonary arterial hypertension occurs by two mechanisms in cardiac<unk> : reduced left heart function due to granulomas weakening the heart muscle or from impaired blood flow. Eye Eye involvement occurs in about 10–90% of cases. Manifestations in the eye include uveitis, uveoparotitis, and retinal inflammation, which may result in loss of visual acuity or blindness. The most common ophthalmologic manifestation of<unk>  is uveitis. The combination of anterior uveitis, parotitis, VII cranial nerve paralysis and fever is called uveoparotid fever or Heerfordt syndrome (). Development of scleral nodule associated with<unk>  has been observed. Nervous system Any of the components of the nervous system can be involved.<unk>  affecting the nervous system is known as neurosarcoidosis. Cranial nerves are most commonly affected, accounting for about 5–30% of neurosarcoidosis cases, and peripheral facial nerve palsy, often bilateral, is the most common neurological manifestation of<unk> . It occurs suddenly and is usually transient. The central nervous system involvement is present in 10–25% of<unk>  cases. Other common manifestations of neurosarcoidosis include optic nerve dysfunction, papilledema, palate dysfunction, neuroendocrine changes, hearing abnormalities, hypothalamic and pituitary abnormalities, chronic meningitis, and peripheral neuropathy. Myelopathy, that is spinal cord involvement, occurs in about 16–43% of neurosarcoidosis cases and is often associated with the poorest prognosis of the neurosarcoidosis subtypes. Whereas facial nerve palsies and acute meningitis due to<unk>  tend to have the most favourable prognosis, another common finding in<unk>  with neurological involvement is autonomic or sensory small-fiber neuropathy. Neuroendocrine<unk>  accounts for about 5–10% of neurosarcoidosis cases and can lead to diabetes insipidus, changes in menstrual cycle and hypothalamic dysfunction. The latter can lead to changes in body temperature, mood, and prolactin (see the endocrine and exocrine section for details). Endocrine and exocrine Prolactin is frequently increased in<unk> , between 3 and 32% of cases have hyperprolactinemia this frequently leads to amenorrhea, galactorrhea, or nonpuerperal mastitis in women. It also frequently causes an increase in 1,25-dihydroxy vitamin D, the active metabolite of vitamin D, which is usually hydroxylated within the kidney, but in<unk>  patients, hydroxylation of vitamin D can occur outside the kidneys, namely inside the immune cells found in the granulomas the condition produces. 1,25-dihydroxy vitamin D is the main cause for hypercalcemia in<unk>  and is overproduced by<unk> coid granulomata. Gamma-interferon produced by activated lymphocytes and macrophages plays a major role in the synthesis of 1 alpha, 25(OH)2D3. Hypercalciuria (excessive secretion of calcium in one's urine) and hypercalcemia (an excessively high amount of calcium in the blood) are seen in <10% of individuals and likely results from the increased 1,25-dihydroxy vitamin D production. Thyroid dysfunction is seen in 4.2–4.6% of cases. Parotid enlargement occurs in about 5–10% of cases. Bilateral involvement is the rule. The gland is usually not tender, but firm and smooth. Dry mouth can occur; other exocrine glands are affected only rarely. The eyes, their glands, or the parotid glands are affected in 20–50% of cases. Gastrointestinal and genitourinary Symptomatic gastrointestinal (GI) involvement occurs in less than 1% of cases (if one excludes the liver), and most commonly the stomach is affected, although the small or large intestine may also be affected in a small portion of cases. Studies at autopsy have revealed GI involvement in less than 10% of people. These cases would likely mimic Crohn's disease, which is a more commonly intestine-affecting granulomatous disease. About 1–3% of people have evidence of pancreatic involvement at autopsy. Symptomatic kidney involvement occurs in just 0.7% of cases, although evidence of kidney involvement at autopsy has been reported in up to 22% of people and occurs exclusively in cases of chronic disease. Symptomatic kidney involvement is usually nephrocalcinosis, although granulomatous interstitial nephritis that presents with reduced creatinine clearance and little proteinuria is a close second. Less commonly, the epididymis, testicles, prostate, ovaries, fallopian tubes, uterus, or the vulva may be affected, the latter may cause vulva itchiness. Testicular involvement has been reported in about 5% of people at autopsy. In males,<unk>  may lead to infertility. Around 70% of people have granulomas in their livers, although only in about 20–30% of cases, liver function test anomalies reflecting this fact are seen. About 5–15% of
Sarcoidosis
Cat-scratch disease
Melioidosis
Tuberculosis
Gamasoidosis
Sporotrichosis
Milk-alkali syndrome
Amyloidosis