Cutaneous manifestations of sarcoidosis in blacks

The diverse patterns of skin lesions occurring in black patients with sarcoidosis are described. Shiny, somewhat waxy papular lesions are the most frequent cutaneous manifestation of sarcoidosis in blacks. Erythema nodosum remains an infrequent finding when compared with the frequency of other cutaneous lesions. Because of its protean cutaneous manifestations, sarcoidosis should be included in the differential diagnosis of all chronic dermatoses in blacks.     

Foreign bodies in granulomatous cutaneous lesions of patients with systemic sarcoidosis

OBJECTIVE: To assess the presence of foreign material in the granulomatous cutaneous lesions of patients with systemic sarcoidosis. DESIGN AND SETTING: Observational study reevaluating histological specimens at a university referral hospital. PATIENTS: Sixty-five patients diagnosed as having sarcoidosis who developed granulomatous cutaneous involvement. MAIN OUTCOME MEASURES: To detect the presence of polarizable foreign particles in cutaneous biopsy specimens and to evaluate the association with clinical features of the patients. RESULTS: Granulomatous cutaneous involvement was demonstrated in 65 (15.3%) of 425 patients with systemic sarcoidosis. In 14 (22%) of the 65 patients, the cutaneous biopsy specimen showed foreign particles in polarized light. The skin lesions corresponded to 3 different clinical patterns: an admixture of papules and infiltration of previously undetected minute scars (n = 6); scar sarcoidosis (n = 4); and subcutaneous nodules (n = 4). The lesions were located most frequently in the extremities, involving the knees in 10 patients. CONCLUSIONS: The presence of polarizable foreign body material in granulomatous cutaneous lesions is not infrequent in patients with systemic sarcoidosis. Inoculation of foreign matter from a previous inapparent minor trauma may induce granuloma formation in individuals with sarcoidosis.     

Cutaneous sarcoidosis in black South Africans

BACKGROUND: It has been observed that, in the USA, sarcoidosis is more common in African-Americans than in other races. It has also been noted that sarcoidosis in African-Americans is characterized by more severe extrapulmonary involvement and more exuberant skin lesions. There is little information on sarcoidosis in black Africans. METHODS: Fifty-four black South African patients with cutaneous lesions of sarcoidosis proven by biopsy were prospectively studied. Dermatologic and ophthalmologic examinations and chest X-rays were performed in all patients. Other investigations relevant in the diagnosis of extracutaneous sarcoidosis were also performed in a variable number of patients. RESULTS: In 40 patients (71%), systemic sarcoidosis was found with lung, eye, and acral bone involvement being most common. Great variations in the morphology of skin lesions were observed. In one-quarter of patients, atypical cutaneous lesions (hypopigmented, ichthyosiform, lymphedematous, mutilating, ulcerative, verrucous) were found. Lupus pernio, once thought to be confined to Northern Europe, was observed in five patients in the subtropical milieu of South African Transvaal. Sarcoidal dactylitis with nail changes was seen in eight patients. Fibrinoid necrosis was found in 12% of the biopsies. CONCLUSIONS: Sarcoidosis in black South Africans is characterized by extensive cutaneous involvement. The lesions are morphologically extremely variable, frequently atypical, and often demonstrate fibrinoid necrosis on histology.     

Specific cutaneous lesions in patients with systemic sarcoidosis: relationship to severity and chronicity of disease

Background. Specific (granulomatous) cutaneous lesions are seen in 9–37% of cases of systemic sarcoidosis, and are usually classified into maculopapules, plaques, lupus pernio (LP), scar sarcoidosis, and subcutaneous sarcoidosis. Their prognostic significance has not been fully established. Aim. To analyse the relationship between the clinical type of granulomatous cutaneous lesions and the systemic features and prognosis of systemic sarcoidosis. Methods. The clinical charts of 86 patients (19 men, 67 women, mean age 46.82 years) with systemic sarcoidosis and granulomatous cutaneous involvement followed up for > 2 years at Bellvitge University Hospital were reviewed. Results. Cutaneous lesions developed before or at the time of diagnosis of systemic sarcoidosis in 80.23% of patients. The main cutaneous lesions were classified as maculopapules (28 patients), plaques (31), LP (6), scar sarcoidosis (7) and subcutaneous sarcoidosis (14). Erythema nodosum (EN) was seen in 30 patients. Radiological stage was 0 for 8 patients, I for 48, II for 24, III for 5 and IV for 1. Systemic sarcoidosis activity persisted for > 2 years in 47 patients, and 42 received systemic corticosteroid treatment for their disease. Maculopapular and subcutaneous sarcoidosis were mainly seen in patients with EN and radiological stage I. Plaques and LP were associated with chronic disease and requirement for systemic corticosteroids. Conclusions. Cutaneous granulomatous lesions are usually present at the diagnosis of systemic sarcoidosis, and the type of cutaneous involvement may have prognostic significance.     

Foreign bodies in sarcoidosis

Sarcoidosis is a multisystem disease of unknown etiology. The demonstration of polarizable foreign bodies in cutaneous granulomas is generally thought to exclude a diagnosis of sarcoidosis. Nevertheless. some investigators have reported systemic sarcoidosis with cutaneous manifestations in which polarizable particles were associated with granuloma formation in the skin. We searched the biopsy specimens of granulomatous lesions from 50 patients with cutaneous sarcoidosis using polarization microscopy to estimate the frequency of polarizable foreign bodies in cutaneous lesions of sarcoidosis. Using electron probe microanalysis, we sought to determine what elements compose these foreign bodies. Polarizable foreign bodies were found in the granulomatous skin lesions of 12 of 50 patients with cutaneous sarcoidosis. All 12 patients also had at least one other granulomatous systemic lesion, and 4 had biopsy specimens of a systemic lesion available for review. Polarizable foreign bodies were found in two cases. The elements identified were calcium, phosphorus, silicon, and aluminum. Polarizable foreign bodies were found in cutaneous sarcoidosis far more often than expected. Foreign bodies were also found in granulomatous systemic lesions. The foreign body may serve as an inciting stimulus for granuloma formation in selected cases of sarcoidosis.     

Cutaneous sarcoidosis: differential diagnosis

Sarcoidosis is a multisystem disease with cutaneous lesions present in 20%-35% of patients. Given the wide variability of clinical manifestations, it is one of the "great imitators," making it necessary to consider clinical, epidemiological, radiographic, laboratory, and histopathological criteria to make the diagnosis. Cutaneous lesions have been classified as specific and nonspecific, depending on the presence of noncaseating granulomas on histologic studies. Specific lesions include maculopapules, plaques, nodules, lupus pernio, scar infiltration, alopecia, ulcerative lesions, and hypopigmentation among others. Nail, mucosal, and childhood sarcoidosis represent a distinct subset of the disease process. The most common nonspecific lesion is erythema nodosum. Others include calcifications, prurigo, erythema multiforme, nail clubbing, and Sweet syndrome. The importance of considering cutaneous sarcoidosis in the clinical differential diagnosis of a given skin lesion relies on the association with systemic involvement and the convenience of the skin as a tissue source for histologic analysis.     

Erythema nodosum-like eruption in sarcoidosis

Two cases of sarcoidosis with tender, erythematous nodules on the legs are reported. The cutaneous lesions were clinically similar to those of erythema nodosum, but histologically showed non-caseating epithelioid granulomas. A review of 14 cases of this particular sarcoid eruption reported in Japan showed that 13 had ocular involvement as in our cases. In the light of the high frequency of ocular involvement, a skin biopsy should be considered in patients presenting with erythema nodosum-like eruptions situated on the legs.     

Polymorphous cutaneous and chronic multisystem sarcoidosis

Sarcoidosis is a systemic disorder in which cutaneous findings are often prominent. These may be polymorphous to the extent that sarcoidosis may mimic many other cutaneous diseases. We describe a 56-year-old woman with involvement of the skin, eyes, bones, heart, and lung. After an initial presentation 10 years earlier of erythema nodosum with bilateral hilar adenopathy, there were three types of cutaneous changes: subcutaneous, nut-sized palpable nodules localized along the upper and lower extremities, annular plaques on the shins, and erythema nodosum-like palpable and slightly tender nodules. It is very unusual to have all three types of skin lesions, especially the erythema nodosum-like histologically specific cutaneous ones in this setting, which is what prompted this report.     

Clinical spectrum and histological analysis of 32 cases of specific cutaneous sarcoidosis

BACKGROUND: Sarcoidosis is a multisystem granulomatous disorder of unknown aetiology in which skin involvement is frequent. OBJECTIVE: To review histological characteristics of biopsies of specific cutaneous lesions of sarcoidosis and their relationship with clinical course. PATIENTS AND METHODS: Biopsies from 32 patients with specific cutaneous sarcoidosis were reviewed. Histological findings and clinical characteristics of these patients were analysed. RESULTS: The initial clinical lesions of the patients were ten infiltrated nodule-plaques, eight papules, four maculopapular eruptions, five scar sarcoidosis, four subcutaneous nodules and one lupus pernio. Sarcoidal granulomas were located at dermis in 31 cases (74%) and at subcutaneous fat in 12 (28%) but only four were subcutaneous exclusively. Perivascular or periannexial distribution of granulomas was observed in eight cases (19%) and they had coalescence in 29 samples. The presence of foreign material was demonstrated in 11 cases (26%). CONCLUSIONS: Clinical spectrum of specific lesions of cutaneous sarcoidosis showed a good correlation with granulomas localization in the biopsies. However, traditional classification of specific cutaneous sarcoidosis is often overlapping. On the other hand, foreign bodies and other atypical histological findings were more common than initially expected.     

Subcutaneous sarcoidosis--clinicopathological study of 10 cases

BACKGROUND: Subcutaneous sarcoidosis is a specific cutaneous lesion of sarcoidosis that is rarely reported. OBJECTIVE: Our purpose was to analyse the clinicopathological features of 10 patients with subcutaneous sarcoidosis and its relationship with the systemic features of the disease. PATIENTS AND METHODS: The patients with systemic sarcoidosis, diagnosed from 1974 to 2002 at a university hospital in Barcelona, Spain, who developed subcutaneous involvement, were included in the study. The diagnosis of systemic sarcoidosis was made according to conventional criteria. All the patients were monitored prospectively at the sarcoidosis clinic of the hospital. Skin biopsies were performed when granulomatous cutaneous involvement was suspected clinically. RESULTS: Granulomatous cutaneous involvement was demonstrated in 85 of 480 patients with systemic sarcoidosis. In 10 of these 85 patients subcutaneous sarcoidosis was diagnosed (11.8%). The lesions were most frequently located in the extremities, involving the forearms in nine patients. Indurated linear bands from the elbow to the hand were observed in five patients. In all of our patients the subcutaneous nodules appeared at the beginning of the disease. In six patients, the nodules remitted spontaneously in less than 2 years. In two cases foreign particles were detected under polarized light. CONCLUSIONS: Subcutaneous sarcoidosis is a quite uniform clinicopathological entity usually appearing at the beginning of the disease. It usually heralds forms of sarcoidosis with nonsevere systemic involvement and is not associated with chronic fibrotic disease.     

The use of tetracyclines for the treatment of sarcoidosis

BACKGROUND: To evaluate the safety and efficacy of minocycline in the treatment of sarcoidosis, a nonrandomized, open study was performed in patients with cutaneous sarcoidosis. OBSERVATIONS: Twelve patients with cutaneous sarcoidosis were treated with minocycline, 200 mg/d, for a median duration of 12 months. Three patients had extracutaneous lesions at the time of the study. The median follow-up was 26 months. A clinical response was observed in 10 patients, consisting of complete responses in 8 patients and partial responses in 2 patients. A progression of skin lesions was observed in 1 patient, and lesions remained stable in another patient. Adverse effects were minimal, except in 1 patient, who developed hypersensitivity syndrome. A slight hyperpigmentation occurred in 2 patients at the site of previous lesions, which completely disappeared after minocycline use was discontinued. A relapse of skin symptoms occurred after minocycline withdrawal in 3 patients, who further received doxycycline, 200 mg/d, allowing a complete remission of lesions. CONCLUSIONS: These results support that minocycline and doxycycline may be beneficial for the treatment of cutaneous sarcoidosis. Randomized controlled studies are warranted for the evaluation of the true efficacy of tetracyclines in these patients.     

Cutaneous sarcoidosis in Nigeria

The study is a retrospective analysis of the cutaneous manifestations of sarcoidosis in patients seen during a 10-year period at the skin and chest clinics of the Lagos University Teaching Hospital. Of the 43 patients with sarcoidosis 30% had skin lesions. The most common was sarcoidal infiltration of scarification marks. Facial macropapular lesions also were frequently present.     

Cutaneous sarcoidosis in Asians: a report of 25 patients from Singapore

Sarcoidosis is a systemic noncaseating granulomatous disorder of unknown origin involving multiple organ systems. There has been no report so far to describe the epidemiological pattern of cutaneous involvement in sarcoidosis in South-East Asia with diverse ethnic groups. A retrospective study examining the clinicopathological features of all patients diagnosed with sarcoidosis at a tertiary dermatology centre in Singapore from 1980 to 2003 was conducted. Cutaneous sarcoidosis was diagnosed in 25 patients: 13 were Indian, 11 were Chinese and one was Eurasian. Cutaneous manifestations included papules, nodules, plaques and scarring alopecia. Extracutaneous involvement of lymph nodes (four patients), lungs (eight patients) and eyes (two patients) was seen. Eight patients had abnormal chest radiographic findings. Histopathological examination of skin lesions revealed noncaseating, epithelioid granulomatous infiltration in the dermis without evidence of mycobacterial infection, deep fungal infection or polarizable birefringent material. Treatment modalities included corticosteroids, hydroxychloroquine, isotretinoin, methotrexate and surgical excision. Five patients had complete resolution of the cutaneous lesions. Cutaneous sarcoidosis is rare in Asia and indeed in Singapore. Extracutaneous involvement is not uncommon and a thorough clinical evaluation should be undertaken.     

Relationship of cutaneous sarcoidosis to systemic disease

Cutaneous sarcoidosis can be represented by an acute, nonspecific process (eg, erythema nodosum) or by a more chronic process represented histologically by the noncaseating granuloma. These manifestations have adequately been documented in other sections of this issue (see chapters 4 and 9). It is the purpose of this section to relate those skin lesions to the potential for internal organ involvement, and the correlation of a particular cutaneous variant with a specific type of organ involvement.

In preparing this section, I began to review the data generated by our practice; then I compared and contrasted it to data reported in the literature. Much of the data is difficult to analyze for a number of reasons. Many of the studies (including ours) have an inclusion bias. For example, patients seen in a pulmonary clinic necessarily have a higher incidence of lung involvement in contrast to those studies seen by dermatologists who may have milder systemic disease. Another problem relates to the inability of a pulmonary specialist to describe the exact nature of the skin lesions or a dermatologist to adequately and thoroughly evaluate the systemic nature of the patient. Despite these biases, this section will deal with studies of systemic disease in patients with cutaneous disease, specifically, lupus pernio, subcutaneous lesions, and the miscellaneous cutaneous manifestations.     

Clinical characteristics of sarcoidosis patients with systemic sclerosis‐specific autoantibody: Possible involvement of thymus and activation‐regulated chemokine and a review of the published works

Sarcoidosis and systemic sclerosis (SSc) are both multisystem disorders of unknown etiology. Some cases having both sarcoidosis and SSc have been reported previously. The present study was to investigate clinical features in sarcoidosis patients who possessed SSc‐specific autoantibody. The pathophysiology of each disease, including shared pathways leading to the development of both conditions, is reviewed in addition to previous reports of patients with concomitant SSc and sarcoidosis. SSc‐specific autoantibodies including anticentromere antibody (ACA), anti‐topoisomerase I antibody, anti‐RNA polymerase III antibody and anti‐U1RNP antibody were examined in sarcoidosis patients. Complete medical histories, clinical examinations and laboratory tests were conducted for all patients. For reviewing previously published reports, all cases were retrieved through a PubMed search. ACA was most frequently observed in sarcoidosis patients. Plaques and papules were the most frequent as the cutaneous sarcoidosis lesions. Soluble interleukin‐2 receptor was elevated in most of the cases (6/8, 75%), and thymus and activation‐regulated chemokine (TARC) was elevated in all cases (6/6, 100%). Together with our two cases (cases 1 and 3), a review of previously reported cases of sarcoidosis patients concomitant with SSc showed high frequency of ACA and plaques as cutaneous lesions. We suppose that TARC may play some roles in the production of SSc‐specific autoantibodies and development of concomitance with SSc in sarcoidosis, although the mechanisms remain unknown.     

Perineural granulomas in cutaneous sarcoidosis may be associated with sarcoidosis small‐fiber neuropathy

Perineural granulomas in cutaneous sarcoidosis have been rarely reported and their clinical significance has yet to be evaluated. Recently, a 27‐year‐old male presented with multiple pink papules on the flank and lower back, accompanied by a painful, burning sensation. Biopsies revealed well‐defined granulomas, consistent with sarcoidosis, in the dermis and involving small cutaneous nerves. We hypothesized that perineural granulomas may be an under‐recognized feature of cutaneous sarcoidosis and may be responsible for sensory disturbances. We reviewed cases from 29 consecutive patients with cutaneous sarcoidosis. Perineural granulomas were identified in 18/29 (62%) patients and in 22/40 (55%) biopsies. Perineural granulomas were identified in 7/9 biopsies from the proximal upper extremity, 1/3 from the distal upper extremity, 7/12 from the head and the neck, including 4/4 from the nose, 5/9 from the back, 1/2 from the flank and 1/1 from the proximal lower extremity and 0/4 from the distal lower extremity. The anatomical distribution is similar to sarcoidosis small‐fiber neuropathy (SSFN), in which sarcoidosis patients without evident skin lesions experience sensory disturbances of unknown etiology involving the face, the proximal extremities and the trunk. Our results indicate perineural granulomas in cutaneous sarcoidosis are more common than previously appreciated, primarily involve the head, the proximal upper extremities and the back, and may be responsible for neurological manifestations.     

Cutaneous sarcoidosis

We report on three clinical cases of cutaneous sarcoidosis. One of them was associated with erythema nodosum, another with erythema annulare centrifugum. The third case showed an annular lesion having persisted for 10 years; X-ray of the lungs revealed stage 3 disease.     

Cutaneous sarcoidosis presenting as a testicular mass

Urologic involvement in sarcoidosis is rare. We report a patient who presented with a testicular mass and, shortly thereafter, manifested nasal lesions of the papular variant of cutaneous sarcoidosis. Histologic examination from both organ systems yielded sarcoidal granulomas. The patient was successfully treated using oral corticosteroids. Sarcoidosis continues to replace syphilis as "the great imitator of the 1990s," and clinicians must be increasingly aware of its variable presentations.     

Cutaneous sarcoidosis treated with levamisole.

16 patients with cutaneous sarcoidosis were treated intermittently over a period of 6 months with levamisole in an open study. The skin lesions cleared in 2 of 13 patients completing the course of treatment. Aggravation of the sarcoidosis was noted in 2 other patients after a few weeks of treatment. Tuberculin sensitivity did not increase during the treatment period. Dinitrochlorobenzene sensitivity increased in 5 patients but the lesions did not clear in any of these patients. It is concluded that levamisole is not useful in the treatment of cutaneous sarcoidosis.     

Clinicopathologic features of ulcerative-atrophic sarcoidosis

BACKGROUND: Sarcoidosis is a chronic granulomatous disease of unknown etiology. Cutaneous disease is common and includes two clinicopathologic categories: granulomatous infiltration or a reactive phenomenon. In the granulomatous infiltrative group, clinical manifestations can be variable. Ulcers in sarcoidosis are uncommonly recognized and have been categorized previously under the rubric of atrophic, necrobiosis-like, or ulcerative sarcoidosis. PATIENTS AND METHODS: We evaluated retrospectively sarcoidosis patients presenting to the Johns Hopkins Department of Dermatology between June 1989 and May 2002. Multiple skin biopsies were performed for histopathologic evaluation. Investigation for extracutaneous manifestations, including routine serologic assays, chest radiography, pulmonary function tests, electrocardiogram, and angiotensin-converting enzyme level, and referral for ophthalmologic examination were performed in all patients. RESULTS: Of 147 consecutive patients presenting with cutaneous sarcoidosis, seven demonstrated ulcerative-atrophic sarcoidosis lesions. All patients were African-American (five females and two males). All patients had ulcers surrounded by atrophic necrobiosis lipoidica-like plaques on the pretibial areas. All patients had other mucocutaneous manifestations of sarcoidosis, with the majority having evidence of internal disease. Combined immunosuppressive and immunomodulatory therapy was effective in controlling the cutaneous manifestations of all patients with ulcerative sarcoidosis. CONCLUSIONS: The ulcerative variant is a poorly defined subset of cutaneous sarcoidosis. Trauma, superimposed on atrophic plaques, appears to be the principal mechanism of this rare variant of cutaneous sarcoidosis.