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--aka sarcoid from Gr "sark" and "oid" means flesh-like
--Besnier-Boeck disease
--immune disorder krkrized by non-caseating granulomas usu in lungs or lymph

PRESENTATION
--often asymptomatic
--symptoms usu appear gradually
--can affect any organ
--varying severity and inconstant distribution means varying presentation
--most often manifests as a restrictive disease of the lungs
----decrease in lung volume & compliance
----higher than normal expiratory flow ratios
----decreased vital capacity (full breath in, to full breath out)
----FEV1/FVC ratio is increased from the normal of about 80%, to 90%
----obstructive lung changes mbdt enlarged lymph nodes in chest, internal inflam or nodules impede airflow
--most pts seek help for resp probs: SOB, cough, chest pain, hemoptysis (hacking dry cough)
--or for general symptoms: fever, fatigue, weight loss, anorexia, night sweats
--peripheral lympyhadenopathy
--curtaneous lesions
--eye involvement (dry eyes, blurry vision: uveitis, uveoparotitis, retinal inflam--> lowered acuity or blindness)
--splenomegaly
--hepatomegaly
--muscle weakness, aches, tenderness, fatigue
--Löfgren syndrome = erythema nodosum, bilateral hilar lymphadenopathy, arthralgia (good prognosis)
--granulomas <--- masses of immune system cells, particularly T cells
--Renal, liver (including portal hypertension), heart or brain involvement more Sx, altered fx
--brain or nerves: neurosarcoidosis
--uveoparotitis = anterior uveitis, parotitis and fever, assoc w/ Heerfordt-Waldenstrom syn
--Hypercalcemia due to excessive activation of vitamin D by epitheliod macrophages

PROGNOSIS
--unpredictable course
--can be progressive & chronic or have remissions
--can remit permanently, spontaneous of induced by steroid therapy
--65-70% of pts recover with minimal or no lasting effects
--20% have permanent loss of some lung fx or permanent visual impairment
--10-15% die of cardiac or CNS damage, progressive pulmonary fibrosis and cor pulmonale
--cor pulmonale = pulmonary hypertensive heart disease (usu R ventricular hypertrophy)
--pts with hilar lymphadenompathy have best prognosis, followed by those with adenopathy and pulmonary infiltrates
--pts with pulmonary disease and no adenopathy have few spontaneous remissions and are most likely to develop chronic pulmonary fibrosis

DIAGNOSIS
--often discovered by accident with chest xray
--bilateral hilar lymphadenopathy or lung involvement on chest radiographs in 90% of cases
--granulomas has central necrosis
--next most common sign: eye and skin lesions
--histologic diagnosis of sarcoidosis is made by exluding mycobacteria, fungi & berylliosis which all can form hard granulomas
--Chest X-ray changes (4 stages)
--1) bihilar lymphadenopathy
--2) bihilar lymphadenopathy and reticulonodular infiltrates
--3) bilateral infiltrates
--4) fibrocystic sarcoidosis typically w/ upward hilar retraction, cystic & bullous changes
--follow-up: electrocardiogram, ocular examination by an optometrist or ophthalmologist, liver function tests, serum calcium and 24-hour urine calcium
--3/4 of pts have spleen changes (microscopic) 1/5 have enlargement
--liver also sometimes involved, less than spleen
--bone marrow is also favored site
--skin lesions in 1/2 to 1/3 of cases, also mucus membranes
--muscle involvement underdiagnosed, asymptomatic/weakness, aches, tenderness, fatigue

PATHOGENESIS
--antigen driven proliferation of T cells
--ratio of CD4:CD8 ranges from 5:1 to 15:1
--increased IL2 and IFNgamma
--70% of pts have Propionibacterium acnes in bronchoalveolar lavage, 25% of controls
--Rickettsia also suggested but no evidence for causal association
--increased macrophage and CD4 helper T-cell activation --> inflam
--suppressed response to antigen challenges such as tuberculin, candida
--paradoxic state suggests anergy
--anergy may be responsible for increased risk of infections and cancer
--appears that regulatory T-lymphocytes in the periphery of sarcoid granulomas suppress IL-2 secretion --?--> state of anergy by preventing antigen-specific memory responses

SUSCEPTIBILITY
--most common in adults under 40 (peak 20-29)
--slightly more common in females
--most prevalent in N. Eur, highest incidence in Sweden, Iceland
--incidence in Africans 35.5:100,000, in Caucasians 10.9:100,000
--rare among Chinese and SE Asians
--in US highest rates in southeast
--working hypothesis: genetically susceptible individuals get sarcoidosis via immune response alteration after exposure to an external agent
--associated with celiac disease
--some cases caused by inhalation of the dust from the collapse of WTC after 9/11/01
--reports of transmission via organ transplant
--familial and racial patterns suggest genetic influence but no gene markers known yet
--siblings have modestly increased risk (hazard ratio 5) to develop sarcoidosis
--associated with MHC class I types: HLA-A1 and HLA-B8

SECONDARY ISSUES
--causes a dysregulation of vitamin D production (increase in extrarenal production); macrophages inside the granulomas activate vitamin D--> elevated levels-->fatigue, lack of strength or energy, irritability, metallic taste, temporary memory loss/cognitive problems
--pt compensate by decreasing parathyroid hormone levels
--to much calcium may also be caused by high levels of estradiol and prolactin (preg)-->hypercalciuria and/or compensatory hypoparathyroidism [14]
--Prolactin frequently increased (3–32% cases develop hyperprolactinemia), may exacerbate symptoms of autoimmune diseases

ALLOPATHIC Tx:
--standard: corticosteroids, esp. prednisone, some pts respond slowly, others no response
--disease may remit spontaneously
--steroids for severe symptoms
--often used: steroid-sparing agents such as azathioprine and methotrexate (and rarely cyclophosphamide)
--some early indications of success using immunosuppressants, interleukin-2 inhibitors or anti-tumor necrosis factor-alpha treatment (such as infliximab). Unfortunately, none of these has provided reliable treatment, and there can be significant side effects such as an increased risk of reactivating latent tuberculosis.
--for hypercalcemia, avoid sunlight and vit D foods

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