SkIndia Quiz 5: Shiny, waxy papules on face and extremities in a female with dyspnea

A 40-year-old woman presented with asymptomatic pinkish red raised lesions over face, neck, and upper extremities since six months. Lesions gradually increased in size and number. She also complained of breathlessness on mild exertion.

Examination revealed multiple, firm, erythematous, and skin-colored papules and plaques distributed over forehead, nose, nape of neck, extensor aspect of forearms, and dorsum of both the hands [Figures 1 and 2]. Her complete hemogram, sparse peripheral smear, antinuclear antibodies, antibodies to ds-DNA, lipid profile, bleeding and coagulation profile, liver function and renal function tests were within normal limits. X-ray of both hands and feet revealed no abnormality. Spirometry showed mild, large and severe small airway obstruction without any bronchodilator response as well as reduced lung diffusion capacity. Computer tomography (CT) scan of thorax revealed interstitial septal thickening with bilateral perihilar and mediastinal lymphadenopathy.

Figure 1.

Erythematous shiny papules over the dorsum of nose

Figure 2.

Skin-colored, waxy papules over the left dorsal hand

Punch biopsy from erythematous papule over right forearm revealed a nodular infiltrate of epithelioid cells, Langhans giant cells, and foamy macrophages in the upper dermis [Figures 3 and 4].

Figure 3.

Biopsy from a papule revealed focal nodular infiltrate of histiocytes and foamy macrophages in upper dermis (H and E, ×200)

Figure 4.

Granuloma consists of multiple Langhans giant cells, epithelioid cells, and histiocytes, some of which are foamy (H and E, ×400)

ANSWER

Diagnosis

Sarcoidosis

DISCUSSION

Sarcoidosis is a multisystem disease commonly involving lungs, liver, spleen, lymph nodes, eyes, and skin. Cutaneous involvement occurs in 20 to 35% of patients with systemic sarcoidosis, though it can also occur in isolation. Genetic factors and infections (Mycobacterium tuberculosis and other mycobacteria) play a role in the etiopathogenesis.[1]

Cutaneous lesions are classified into specific and nonspecific lesions based on the presence of noncaseating epithelioid granulomas on skin biopsy. Specific lesions include papules, plaques, nodules, lupus pernio, scar sarcoidosis, hypopigmented macules, erythroderma, alopecia, and other rare forms. These types are more chronic and tend to resolve with scarring. Nonspecific lesions include erythema nodosum, erythema multiforme, prurigo, calcifications, nail clubbing, etc.[2,3]

Histologically, sarcoidosis is characterized by the presence of non-caseating epithelioid cell granulomas and peripheral cuffing by lymphocytes.[4] Noncaseating granulomas with dense lymphocytic infiltrate, fibrinoid necrosis in center of granuloma, well-demarcated elastophagocytosis within the naked granulomas, and mucin deposition in center of granuloma are other unusual histological variants.[5–7] In our case, the granuloma was focal, small, and composed of epithelioid cells, foamy histiocytes, and Langhans giant cells. These granulomas were neither associated with appendages nor with vasculitis. There was no evidence of any foreign body or organisms. Overlying epidermis was normal. Foamy change noted in the granuloma was an unusual finding. Foamy change of histiocytes is an indication of the phagocytic activity of macrophages and the presence of phagolysosomes containing foreign body or organisms or lipid material. However, such a change in sarcoidosis is intriguing and needs further confirmation by larger histopathological studies of sarcoidosis. Hypergammaglobulinemia and raised angiotensin-converting enzyme levels (our case, 246 u/l; normal 8-52 u/l) correlate with the disease activity. Sarcoid granulomas are known to produce 1,25-dihydroxyvitamin D and hence, there is a risk of nephrocalcinosis.[1,7] Roentgenogram of chest reveals hilar lymphadenopathy and calcification of lymph nodes imparting eggshell-like appearance. X-ray of hands and feet often reveal bone cysts (however, absent in present case). Hilar lymphadenopathy and lung involvement can be assessed by CT scan of chest. Gallium uptake in the nasopharynx, lacrimal and parotid glands is called Panda sign and uptake in perihilar lymph nodes is called Lambda sign.[8] In our patient, above discussed histological changes and investigations helped us in excluding other differential diagnoses like cutaneous tuberculosis, tuberculids, foreign body granulomas, and xanthomas.

The treatment of cutaneous sarcoidosis is often unyielding due to high relapse rate. Localized lesions are treated with topical or intralesional steroids, whereas systemic involvement requires systemic corticosteroids, immunosuppressants, antimalarials, or biological agents (etanercept, infliximab, and alefacept).[1,9]