Sarcoidosis

SARCOIDOSIS It is a systemic granulomatous disease of undetermined etiology. The important features are ---1. The characteristic and similar histopathology should be present in all tissues 2. The process is usually generalized and widespread and any organ of the body ay be affected. THE MOST FREQUENTLY AFFECTED ORGANS ARE THE LYMPH NODES, LUNGS, LIVER, SPLEEN, SKIN, EYES, SMALL BONES OF THE HANDS AND FEET AND SALIVARY GLANDS. 3. A varying and inconstant degree of suppression or weakening of tuberculin and other ID responses and raised immunoglobulin and calcium levels and other changes are present. 4. The positive reaction of Kviem test in most active cases. Though etiology is unknown, yet 2 main areas of speculation are ---------- unusual host response to infectious (mycobacteria, mycoplasma, borrelia, P.acnes, histoplasma, Cryptococcus, EBV, CMV, HSV, rubella) or noninfectious (aluminium, zirconium, talc, pine tree pollen and clay) agent and genetic factors (familial cases of sarcoidosis are known to occur). HPE: The characteristic feature is the presence of CIRCUMSCRIBED EPITHELOID GRANULOMAS WITH LITTLE OR NO CASEATION NECROSIS. A few multinucleate giant cells are usually but not invariably present though they may be present in large numbers in older lesions. Small deposits of fibrin can be present. Only sparce infiltrates of lymphocytes are present in the periphery of these granulomas --------- hence the name “naked granulomas”. 3 types of inclusion bodies are observed within the giant cells but are non specific ---------

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Schaumann bodies ---- basophilic concentric lamellar structures 100 micrometer in diameter. It is composed of lipomucoglycoproteins impregnated with calcium and iron and showing central birefringent crystals.

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Asteroid bodies ---- measuring between 10 and 15 micrometer in size, with their central core being surrounded by radiating spicules composed of collagen.

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Residual bodies ---- composed of lipomucoprotein granules.

The granuloma occurs lower in the dermis than in LV and are usually scattered throughout the dermis with occasional extension to the panniculus. Immunological aspects --- Depressed CMI is the hallmark ---- Depression of sensitivity to tuberculin. This anergy extends to other ID allergens like candida, pertussis, trichophyton and mumps antigens. Response to DNCB is also defective.  The levels of circulating suppressor T lymphocytes are increased in sarcoidosis and correlate with the defect in CMI  All classes of Igs are raised  Immune complexes are present in more than 50% of sarcoid patients and are manifested clinically by EN, POLYARTHRITIS AND UVIETIS. SARCOIDOSIS OF SKIN Skin lesions occur in approximately 20-40% of patients with systemic sarcoidosis but cutaneous sarcoidosis can also occur without systemic involvement. 2 TYPES OF CUTANEOUS LESIONS ARE RECOGNIZED ------------

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SPECIFIC CUTANEOUS SARCOIDAL LESIONS --- associated with a more chronic and less favourable course. They comprise of dense collections of epitheloid granulomas in the dermis. The SC tissue is involved by extension in the deep infiltrative lesions. MAJORITY OF SPECIFIC LESIONS ARE PAPULES AND PLAQUES. THEIR COLOUR RANGES FROM YELLOW OCHRE TO LIVID VIOLACEOUS HUE AND ON DIASCOPY A PALE YELLOW-GREY COLOUR REMAINS. NONSPECIFIC NONSARCOIDAL REACTIVE LESIONS ---- associated with acute but more benign disease.

FORMS OF PRESENTATION: 1. Angiolupoid form 2. Annular form 3. Lupus pernio 4. maculopapular and erythematous form 5. nodular forms 6. papular forms 7. plaque forms 8. Scar sarcoid 9. EN 10. atypical forms --- erythrodermic, ichthyosiform, atrophic, ulcerating, verrucous,hypopigmented and alopecic, SC nodules. ANGIOLUPOID FORM: It is a rare but characteristic form that occurs in women. It generally consists of one or two soft hemispherical lesions of reddish brown or more livid hue (due to marked telangiectatic component). They are seen mostly at the side of the bridge of nose toward the corner of the eye below the inner edge of the eyebrow or on the adjacent area of cheek. There is little tendency to spontaneous resolution. LUPUS PERNIO: It is a relatively common type of cutaneous sarcoid occurring in older patients and twice commoner in women. They are bluish red glistening nodules and plaques occurring in the nose, cheeks, ears, fingers, hands and toes. When the surface is stretched large pilosebaceous follicles are seen. Rarely ulcerations can occur. Massive swelling of ears (turkey ears) and nasal vestibule can occur with ulceration and crusting. Lupus pernio can be associated with other forms of chronic fibrotic sarcoidosis including respiratory tract sarcoidosis, pulmonary sarcoidosis, bone cysts, lacrimal gland sarcoidosis, chronic uvietis and renal sarcoidosis. IT TENDS TO PERSIST FOR LONG.

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NAIL INVOLVEMENT RARE Occurs in association with chronic sarcoidosis Presents mostly as dystrophic changes of the nail plate -------- pitting, cracking, longitudinal ridging, fragility, opacity and loss of nail plates. Such changes are usually associated with lupus pernio, sarcoid dactylitis and cystic bone changes of the phalanx. MUCOSAL INVOLVEMENT

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Diffuse pale yellow plaques, nodules or ulceration are seen in the buccal mucosa, palate, larynx or tongue. Involvement of nasal mucosa is found in lupus pernio. Nasal bones may be involved and nasal cartilage may collapse.

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RETICULOENDOTHELIAL SYSTEM Lymph nodes are involved in 50% cases. Most frequently involved are ----- HILAR AND PARATRACHEAL Any of the superficial LN may be involved

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Enlargement of liver and spleen occurs in some

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EYES involved in 25-50% cases eyes should be examined with slit lamp since mild asymptomatic involvement is commoner. Uvietis is the most frequent symptomatic manifestations. Anterior uveitis is usual in the acute variants of sarcoid whereas posterior uveitis is commoner in the chronic variants. Complications include glaucoma, cataract and iris synechia. Other manifestations ----------- keratoconjunctivitis sicca, phlyctenular conjunctivitis, Mikulitz syndrome (bilateral swelling of Lacrimal and salivary glands). UPPER RESPIRATORY TRACT

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It is uncommon but very disabling manifestation of the disease. It affects the nose, masopharynx and the larynx. Involvement occurs as crusting, discharge and obstruction. Cartilage or bone may be destroyed.

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UVEOPAROTID FEVER It is a febrile illness characterized by uveitis and swelling of parotids accompanied frequently by facial palsy.

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NERVOUS AND ENDOCRINE SYSTEMS Peripheral neuropathy Cranial neuropathy Meningoencephalitis SOL Epilepsy Lymphocytic meningitis Diabetes insipidus Hypopitiutarism

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SKELETAL SYSTEM Bone changes are often asymptomatic and can be detected by routine radiologic examination. Commonly involves bones of hands and feet in a middle aged women with lupus pernio ---- punched out bone cysts are most common. Sometimes diffuse infiltration of the Phalangeal shaft and destruction of cortical and medullary bone are occasionally seen. SC tissue swellings affecting several fingers and toes are frequently associated and add to the disability. Sarcoid arthritis has also been described.

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GENITOURINARY SYSTEM Kidneys are affected in 2 ways ----------- one is occurance of sarcoidal granulomas in the kidneys and the other is nephrocalcinosis ( in sarcoidosis there is increased calcium absorption from the gut due to an unexplained increase in sensitivity to vit D.

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CARDIOVASCULAR SYSTEM Affected in 2 ways: extensive pulmonary fibrosis can lead to cor pulmonale while direct myocardial involvement leads to dysrrthymias, conduction disorders, heart failure or sudden death.

PULMONARY CHANGES  Most common form of sarcoidosis  It is classified into 4 stages ----Stage 0: 5-10% of patients with sarcoidosis have a normal CXR Stage 1: Bilateral hilar lymphadenopathy in 35-45% of cases Stage 2: Bilateral hilar lymphadenopathy with parenchymal lung involvement of the fluffy or coarse type Stage 3: Late stage of pulmonary infiltration with fibrosis and pulmonary insufficiency. INVESTIGATIONS: 1. Tissue biopsy 2. Kveim Test --- the basis of Kveim test is that particulate saline suspensions of sarcoid tissue injected ID in a patient with active sarcoidosis may provoke the slow development of an epitheloid cell granuloma of sarcoid type. IT IS A HIGHLY SPECIFIC TEST. The test is performed by injecting 0.1-0.2 ml of a suspension of human sarcoid tissue ID usually into forearm, within 2-3 weeks a positive test will show a purplish red nodule at the site of injection ---- biopsy at 4-6 weeks reveals a sarcoid granuloma. AS THE DISEASE BECOMES CHRONIC, POSITIVITY BECOMES LESS COMMON. 3. CXR 4. hand X rays

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ACE test ---- serum levels of ACE are raised in about 60% of patients because ACE is produced by sarcoidal granulomas. It is non specific since it is also raised in DIABETES AND ALCOHOLIC LIVER DISEASE. 6. HYDROXYPROLINURIA indicates disease activity. Also levels of ICAM-1 7. ECG 8. Pulmonary function tests 9. ESR raised 10. Radioactive gallium 67 uptake occurs in some pulmonary infections, neoplasms as well as sarcoidosis. 11. Blood biochemistry ----- Hypochromic microcytic anemia, leucopenia, moderate eosinophilia, hypercalcemia and hypergammaglobulinemia.

D/D: Lupus vulgaris, leprosy, syphilis, tinea corporis, plaque psoriasis, LP, LE, lymphocytoma cutis, NLD, GA, Granuloma faciale, Drug eruption. Histological D/D of naked granulomas are -------- LV, foreign body granuloma, leprosy and lymphoma. LEPROSY AND FOREIGN BODY REACTION ARE USUALLY THE MOST DIFFICULT TO DIFFRENTIATE FROM SARCOIDOSIS. TREATMENT: Corticosteroids are the mainstay. Topical or IL are tried only in cutaneous involvement whereas oral steroids are used in systemic cases (lung, nervous involvement). In cases where steroids are ineffective or contraindicated ---------- cytotoxic agents are used. In chronic cutaneous forms of sarcoidosis -------- antimalarials are useful. Thalidomide is useful in steroid resistant cases.