April 2004

Fig.2

Fig.3

Diagnosis: Subcutaneous sarcoidosis (Darier-Roussy type)

Histopathology:
Numerous "naked," non-caseating, epithelioid granulomas. AFB and GMS stains were negative. See photos 1, 2, 3, 4.

Discussion:
Sarcoidosis is a granulomatous disorder of unknown etiology that generally affects multiple organ systems. The highest incidence in the world occurs in Sweden (64/100,000). In the United States, the racial variation is 10/ to 14/100,000 for Caucasians and 35/ to 64/ 100,000 for African Americans; females have a higher incidence than their respective male counterparts in each racial group. Current theories regarding its pathogenesis include immunologic (TH1 milieu), genetic (association with certain HLA alleles on chromosome 6), infectious (conflicting data on mycobacterial DNA by PCR), and environmental.

Cutaneous manifestations occur in around 25% of cases and generally at the onset. Aside from erythema nodosum, which generally correlates with a more acute self-limited course, cutaneous lesions do not have any correlations with the extent and severity of the disease. Specific cutaneous manifestations include maculopapules, nodules, plaques, subcutaneous nodules, and lupus pernio (indurated, dusky red, shiny skin changes occurring on the nose and face which may be destructive).

There are four specific syndromes seen in sarcoidosis. Löfgren's syndrome consists of acute sarcoidosis, erythema nodosum, migratory polyarthritis, fever, and iritis. As mentioned previously, this form is self-limited and generally resolves without therapy. Heerfordt-Waldenström syndrome consists of fever, parotid enlargement, anterior uveitis, and facial nerve palsy. This syndrome can be followed by neurologic sequelee. Mikulicz's syndrome consists of bilateral sarcoidosis of the parotid, submandilbular, sublingual, and lacrimal glands. Darier-Roussy type is characterized by multiple subcutaneous nodules on the trunk and extremities.

Sarcoidosis is a diagnosis of exclusion. If clinically suspicious skin lesions are present, a biopsy should be performed. The histopathology of sarcoidosis should show granulomas composed of epithelioid histiocytes and multinucleate giant cells with only a sparse infiltrate of lymphocytes at the periphery ("naked" granulomas). These granulomas are in superficial dermis but may extend into the deep dermis or the sub cutis. AFB stains should be done to rule out mycobacterial infections. If sarcoidosis is suspected additional workup should include serum liver function tests, BUN, creatinine, CBC, ESR, and calcium to identify possible multi-organ involvements. A PPD should be placed to rule out TB. A chest x-ray and pulmonary function test should be performed to rule restrictive patterns. An EKG should be performed since sarcoidal infiltrations of the heart can rarely cause heart block. A full ophthalmologic exam should be performed to rule out uveitis, which can result in blindness.

Treatment for cutaneous sarcoidosis are divided into topical and systemic treatments. Topical treatments such as topical and intralesional steroids for may be effective for limited skin involvements. For severe or recalcitrant disease, systemic treatments may be more effective. Traditional systemic modalities have included glucocorticoids, hydroxychloroquine, methotrextate, allopurinol, thalidomide, retinoid, melatonin, and PUVA. A recent case series reported treatment success with minocycline at a dose of 500 mg BID. Finally, current insight into the pathogenesis of sarcoidosis as a TH1 mediated condition have led some to suggest the use of TNF inhibitors. Only a few reported cases with favorable outcomes have been published so far and more research in this area needs to be done.

References:
Bachelez, H et al. The Use of Tetracyclines for the Treatment of Sarcoidosis. Arch Dermatol 2001;137:69-73.
English III, J et al. Sarcoidosis. J Am Acad Dermatol 2001;44:725-43.
Moller, DR. Treatment of sarcoidosis ­ from a basic science point of view. J Int Med 2003;253:31-40.