A. Characteristics

1. Non-caseating granulomas
   1. Non-necrotic granulomas: non-caseating means non-"cheese-like"
   2. TB also has granulomas, but these do caseate (necrose) in most cases
   3. Other non-caseating granulomatous disease include Crohn's Disease, idiopathic disease
2. Affects lung interstitium: restrictive disease
3. Lymph nodes (hilar) which may become calcified
4. Lesions can appear almost anywhere
5. May present initially as painful polyarthritis
   1. Acute painful polyarthritis, usually hands or ankles
   2. May have chronic polyarthritis as well

B. Symptoms and Signs

1. Shortness of Breath
2. Hemoptysis
3. Skin Lesions
   1. Hypopigmented papular (bumpy) skin lesions
   2. Also get hyperpigmented, macular lesions
   3. Erythema nodosum (red, nodular lesions) - inflammation of subcutaneous fat
   4. Rash may have lupus pernio (looks like frostbite) form
4. Can get CNS (especially cranial nerve) involvement
   1. Bell's Palsey (CN VII) not uncommon
   2. CN III and VI not uncommon
5. Uveitis - typically anterior disease (iridocyclitis)
6. Liver Disease - granulomatous, often with obstructive symptoms
7. Polyarthropathy / arthritis
   1. Small joints of hands, wrists
   2. May involve ankles, feet
   3. Quite painful

C. Staging of Lung Lesions

1. Stage I: Perihilar Lymph node enlargement
2. Stage II: LN and lung parenchyma
3. Stage III: Lung parenchyma only
4. Stage IV: Complete lung destruction with Fibrosis (End Stage Lung Disease)

D. Etiology and Diagnosis

1. Abnormal CD4 cells at point of eruption have been demonstrated (human Vß8 implicated)
2. Often have a reversal in serum CD4:CD8 T cell ratio, from normal ~2 to ~0.8
3. Diagnosis usually requires biopsy
   1. Skin lesions are easiest to biopsy
   2. Bronchoscopy may be required
4. Ophthalmological examinations should be performed evey 6 months to 2 years
5. Peripheral leukopenia, relative depletion of CD4 cells
6. Isolated increase of alkaline phosphatase (± bilirubin) for liver involvement
7. ACE levels increase in ~50% of patients (non-specific)
8. Kveim challenge test is rapidly becoming obsolete

E. Therapy

1. Glucocorticoids for Lung Disease
   1. Prednisone, initially 50-60mg qd, tapered to 5-15 q.d. after 1-2 months
   2. Most patients can be controlled 10-15mg prednisone q.d. with little or no side effects
   3. Asymptomatic patients should generally not be treated
2. Indications for treatement of lung disease
   1. Symptomatic lung involvement
   2. CNS sarcoid (independent of symptoms) - cytotoxic agents may be required
   3. Uveitis should be treated
   4. Liver disease does not respond to steroids
3. Therapy for Sarcoid Arthritis
   1. May respond to NSAIDs in high doses (consider safety aspects)
   2. Low dose prednisone very effective
   3. Consider methotrexate 7.5-20mg po or sc weekly for difficult cases
4. Methotrexate may also be used for steroid sparing activity in lung/other disease

F. Lofgren's Syndrome [3]

1. Components of Syndrome
   1. Sarcoid with hilar lymphadenopathy or pulmonary infiltration
   2. Erythema nodosum
   3. Ankle arthritis / periarthritis and/or arthralgia
   4. All three findings are present in ~25% of patients at presentation
2. Other Findings
   1. Fever
   2. Cough or dyspnea
   3. Hepatomegaly (splenomegaly is rare)
   4. Peripheral adenopathy
3. Most common in Caucasians (rare in blacks)
4. May be more common in young women
5. Chest radiologic stages I and II were always (no Stage III or IV)
6. Biopsy of skin lesions with typical chest radiography is most common diagnostic
7. Rarely progresses to chronic disease: ~90% undergo spontaneous remission
8. May be treated with NSAIDs or low dose prednisone with rapid taper

References

1. Pettersson T. 1998. Curr Opin Rheumatol. 10(1):73
2. Totemchokchyakarn K and Ball GV. 1997. Bull Rheum Dis. 46(3):3
3. Mana J, Gomez-Vaquero C, Montero A, et al. 1999. Am J Med. 107(3):240