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Cutaneous manifestations of sarcoidosis

Cutaneous manifestations of sarcoidosis
Literature review current through: Jan 2024.
This topic last updated: Dec 04, 2023.

INTRODUCTION — Sarcoidosis is a granulomatous disease characterized by the presence of noncaseating granulomas in organs and tissue, such as the skin, lung, lymph nodes, eyes, joints, brain, kidneys, and heart. Cutaneous lesions may present with a variety of morphologies, including papules, nodules, plaques, and infiltrated scars (picture 1A-J).

The diagnosis of cutaneous sarcoidosis is supported by the recognition of compatible clinical features, the detection of classic histopathologic findings, and the exclusion of other granulomatous disorders. Compared with other sites of sarcoidal involvement, histopathologic sampling of lesions in the skin is a relatively simple and safe procedure. When present, cutaneous lesions can be a valuable asset in the confirmation of a diagnosis of sarcoidosis.

In addition to skin lesions that display noncaseating granulomas on biopsy, cutaneous eruptions that are not specific for sarcoidosis may also occur in patients with sarcoidosis. Erythema nodosum is the most frequent nonspecific cutaneous disorder associated with sarcoidosis.

The clinical manifestations and diagnosis of cutaneous sarcoidosis will be discussed here. The management of cutaneous sarcoidosis, the pathogenesis of sarcoidosis, and the manifestations of extracutaneous sarcoidosis are reviewed elsewhere.

(See "Cutaneous sarcoidosis: Management".)

(See "Pathology and pathogenesis of sarcoidosis".)

(See "Clinical manifestations and diagnosis of sarcoidosis".)

(See "Overview of extrapulmonary manifestations of sarcoidosis".)

CLASSIFICATION — Skin manifestations of sarcoidosis are estimated to occur in approximately 25 percent of patients and are divided into specific and nonspecific lesions based on histopathologic features [1-7]. Patients may have both specific and nonspecific skin findings [8].

Specific lesions – Specific skin lesions contain noncaseating (sarcoidal) granulomas, which represent the classic histopathologic findings in lesional tissue. Specific lesions are estimated to occur in 9 to as many as 36 percent of patients with sarcoidosis, depending upon the characteristics of the evaluated population and study design [8,9]. Although their histopathologic features are similar, the clinical manifestations of specific lesions vary widely. Papules, nodules, plaques, and infiltrated scars are among the most common presentations; other manifestations also occur [9,10]. (See 'Specific lesions' below and 'Histopathology' below.)

Nonspecific lesions – All other cutaneous findings associated with sarcoidosis are classified as nonspecific. The nonspecific lesions of sarcoidosis include a wide spectrum of disorders.

Erythema nodosum, which typically presents as inflammatory, tender nodules on the lower legs, is the most common nonspecific cutaneous lesion of sarcoidosis. In one study of 516 patients with sarcoidosis, erythema nodosum was present in 20 percent of all patients and in 62 percent of patients with cutaneous disease [9]. (See 'Erythema nodosum' below.)

Other examples of nonspecific cutaneous manifestations include calcinosis cutis, Sweet syndrome, and nail clubbing [7,11]. (See 'Nonspecific lesions' below.)

Although some authors have considered erythema multiforme a nonspecific manifestation of sarcoidosis [12], there is little evidence to support a definitive link between sarcoidosis and erythema multiforme.

EPIDEMIOLOGY — The incidence and prevalence of sarcoidosis vary across populations [13]. Sarcoidosis is primarily a disease of adults but may also occur in children. General epidemiologic data for sarcoidosis are reviewed separately. (See "Clinical manifestations and diagnosis of sarcoidosis", section on 'Epidemiology'.)

The epidemiology of cutaneous sarcoidosis has not been well studied. Although some studies suggest that sarcoidosis is more common in females and has a younger age of onset in males, data are insufficient for conclusions on age or sex predilection for cutaneous disease. In one retrospective study of 1429 patients with sarcoidosis in a pulmonary clinic in Sweden, female patients were more likely to have cutaneous involvement than male patients (13 versus 8 percent) [14]. Some data suggest that compared with adults, cutaneous involvement may be more common in children [15]. (See "Clinical manifestations and diagnosis of sarcoidosis", section on 'Epidemiology'.)

Although racial variation in risk for sarcoidosis has been reported, the reasons and implications of these observations remain unclear. Such observations may be influenced by factors such as socioeconomic status, occupation, education, barriers to care, or other environmental and social factors [13,16]. Whether the prognosis of patients with cutaneous involvement differs among populations also remains to be determined. In a small retrospective study of patients in the United States in whom sarcoidosis was first diagnosed through cutaneous disease (n = 50), Black patients were more likely to have extracutaneous involvement and cardiac involvement compared with non-Black patients [17]. (See "Clinical manifestations and diagnosis of sarcoidosis", section on 'Epidemiology'.)

PATHOGENESIS — The factors that lead to the development of sarcoidosis are not well understood. The pathogenesis is thought to involve genetically influenced dysregulation of the T helper type 1 (Th1) immune response to one or more extrinsic antigens, an event that could lead to the overactivation of inflammatory pathways and subsequent granuloma formation [18,19]. (See "Pathology and pathogenesis of sarcoidosis".)

Multiple foreign bodies, infectious agents, and medications have been proposed as potential contributors to the development of sarcoidosis [18,20-23]. Polarizable material may be seen in 20 to 78 percent of skin biopsies of sarcoidosis, most commonly with papular, scar, and subcutaneous nodular types [20,23,24]. It is unknown whether environmental factors that come in contact with the skin serve as a nidus for granuloma formation or stimulate an aberrant immune response through other mechanisms [18,19,25]. Additional studies are necessary to explore the pathogenesis of cutaneous sarcoidosis.

HISTOPATHOLOGY

Findings — The characteristic histopathologic finding in specific lesions of cutaneous sarcoidosis is the presence of sarcoidal noncaseating granulomas.

Noncaseating granulomas – Sarcoidal noncaseating granulomas consist of aggregates of epithelioid histiocytes, giant cells, and mature macrophages (picture 2A-B) [26]. These granulomas are surrounded by sparse lymphocytic infiltrates composed primarily of CD4+ T cell lymphocytes and a few CD8+ lymphocytes. The absence of a dense lymphocytic infiltrate, such as is common in cutaneous lesions of tuberculosis, has led to the use of the term "naked granulomas" to describe this classic histopathologic finding in sarcoidosis.

The giant cells located within sarcoidal granulomas may contain intracytoplasmic inclusions. These structures are found in other granulomas and are not pathognomonic of sarcoidosis [4]:

Asteroid bodies – Stellate, eosinophilic inclusions made up of complex lipids.

Schaumann (conchoidal) bodies – Round or oval inclusions consisting of laminated calcium oxalate; these may represent residual bodies of lysosomes.

Crystalline inclusions – Colorless, round or oval, refractile, nonlaminated inclusion bodies composed of calcium oxalate that may represent precursors of Schaumann bodies.

Other potential findings – The histopathologic diagnosis of sarcoidosis is complicated by the fact that not all lesions of sarcoidosis demonstrate classic histopathologic findings [4,23,26-32]. While naked granulomas have been strongly associated with sarcoidosis, they are not always present. It is estimated that 71 to 89 percent of specific lesions of sarcoidosis contain typical sarcoidal granulomas [4,23,33]. Occasional cases of sarcoidosis may exhibit florid lymphocytic infiltrates at the periphery of granulomas, central caseation, vasculitis, or increased dermal mucin [4,23,26-32].

Epidermal changes are present in some histopathologic specimens of sarcoidosis and are dependent upon lesion type. Atrophy and parakeratotic scale are the most common epidermal changes detected. Epidermal spongiosis, hyperplasia, and ulceration are present occasionally.

Additional study is necessary to confirm whether certain histologic findings have clinical relevance. In a Spanish retrospective study of 41 patients with cutaneous sarcoidosis, the presence of a moderate or severe granulomatous infiltrate in biopsy specimens was associated with more severe clinical presentations of disease, more generalized disease, and a more chronic disease course [34].

Differential diagnosis — The differential diagnosis of specific lesions of cutaneous sarcoidosis includes a variety of other disorders that may exhibit granulomas on histopathologic examination.

Infectious disorders – Deep fungal infections, mycobacterial infections, and other infections should be considered in the histopathologic differential diagnosis of cutaneous sarcoidosis. Microbial stains and fresh tissue cultures can assist with ruling out these diagnoses. Examples include:

Tuberculosis (lupus vulgaris variant) – The histopathologic features of lupus vulgaris can closely resemble sarcoidosis. A granulomatous infiltrate located primarily in the upper dermis, a more prominent peripheral lymphocytic inflammatory infiltrate, and the presence of significant central necrosis in granulomas suggest a diagnosis of lupus vulgaris. Lesions of lupus vulgaris may also demonstrate ulceration, acanthosis, and pseudoepitheliomatous hyperplasia. A negative acid-fast stain does not rule out lupus vulgaris. (See "Cutaneous manifestations of tuberculosis".)

Tuberculoid leprosy – Granulomas in tuberculoid leprosy are often elongated and located along the course of nerves. Unlike in sarcoidosis, central caseation is a common feature of granulomas in tuberculoid leprosy. Acid-fast stains reveal the presence of acid-fast bacilli in a minority of cases of tuberculoid leprosy. (See "Leprosy: Epidemiology, microbiology, clinical manifestations, and diagnosis".)

Examples of other diseases in the differential diagnosis include infections due to nontuberculous mycobacteria (eg, Mycobacterium marinum, M. kansasii, M. chelonae, M. fortuitum, M. ulcerans, M. abscessus, M. avium complex, M. xenopi), brucellosis, tularemia, bartonellosis, aspergillosis, histoplasmosis, blastomycosis, coccidiomycosis, cryptococcosis, granulomatous herpes zoster, toxoplasmosis, leishmaniasis, echinococcosis, and enterobiasis [35].

Noninfectious disorders – Foreign body reactions, drug reactions, and other noninfectious disorders are in the histopathologic differential diagnosis of cutaneous sarcoidosis.

Foreign body reactions – The identification of refractile material with polariscopic examination of a histopathologic specimen suggests a foreign body reaction. Giant cells with multiple nuclei in a haphazard arrangement (foreign-body giant cells) are often present.

Examples of substances that may trigger granulomatous foreign body reactions include talc, starch, beryllium, titanium, nickel, aluminum, palladium mercury, silicone, zinc, oxalate, gel foam, biomaterials, cactus bristles, wood splinters, surgical sutures, pencil lead, artificial hair, insect mouthparts, cardiac pacing wires, and soft tissue fillers. (See "Injectable soft tissue fillers: Permanent agents" and "Injectable soft tissue fillers: Temporary agents".)

Drug-induced sarcoidosis-like reactions – Drug-induced sarcoidosis-like reactions are indistinguishable from sarcoidosis and occur in temporal relationship with initiation of a drug. (See 'Drug-induced sarcoidosis-like reactions' below.)

Other possible causes of noninfectious cutaneous granulomas include sarcoid-like reaction to tumors, lymphoma, lymphomatoid granulomatosis, antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis, rheumatoid nodules, Langerhans cell histiocytosis, immunoglobulin G4 (IgG4)-related disease, inflammatory bowel disease, orofacial granulomatosis, and Blau syndrome [35].

ASSOCIATION WITH SYSTEMIC DISEASE — Because there are no large, well-designed studies, the risk for the development of systemic involvement in patients who present with disease limited to the skin is unknown [36,37]. Systemic involvement is estimated to occur in 30 to 85 percent of patients with cutaneous sarcoidosis [38]. Cutaneous disease can be the initial sign of sarcoidosis; in a retrospective study of 18 patients with cutaneous sarcoidosis in Ireland, 12 patients (67 percent) had cutaneous lesions as the initial presentation of sarcoidosis [39].

Patients with the lupus pernio variant of cutaneous sarcoidosis or sarcoidosis manifesting in scars appear to have a high risk for pulmonary disease. In a retrospective study of 516 patients with sarcoidosis, pulmonary parenchymal involvement was present more frequently in patients with lupus pernio or sarcoidosis involving scar tissue (64 and 40 percent, respectively) than in patients with erythema nodosum or other specific lesions of sarcoidosis [9]. (See 'Lupus pernio' below.)

Isolated cutaneous disease might have a more favorable prognosis than the combination of cutaneous and systemic disease. In a Spanish retrospective study of 41 patients with cutaneous sarcoidosis who were followed for 3 months to 21 years (median 4 years), patients with isolated cutaneous involvement were less likely to have documentation of persistent disease activity for more than two years (29 versus 92 percent), and eventual complete resolution of skin lesions was more frequent in patients with isolated cutaneous disease (77 versus 33 percent) [34].

SPECIFIC LESIONS — Specific eruptions of sarcoidosis are characterized by the presence of sarcoidal granulomas on histopathologic examination. Specific lesions may occur in a variety of morphologies but most commonly appear as papules or nodules. Lesions are often asymptomatic [40].

In children, the most common specific eruptions are papular, consisting of flat-topped papules, usually on the face. However, the entire spectrum of clinical cutaneous sarcoidosis has been described in children [41,42].

Impact of skin color — The color of sarcoidosis skin lesions varies widely and may include shades of pink, red-brown, yellow-brown, purple-brown, or gray [16]. In individuals with highly pigmented skin, the erythema associated with cutaneous inflammation is often more subtle than in individuals with lightly pigmented skin.

Papular sarcoidosis — Papular sarcoidosis is a common specific cutaneous manifestation of sarcoidosis (picture 1E, 1K) [12].

Clinical features – Papular sarcoidosis presents with numerous nonscaly, 1 to 10 mm papules. Lesions can be skin colored, yellow-brown, red-brown, violaceous, or hypopigmented. In some cases, the papules demonstrate a slight central depression [12]. Although papules can develop in chronic disease, this form of sarcoidosis is more common in patients with acute disease [6].

Papular sarcoidosis most frequently occurs on the face, with a predilection for the eyelids and nasolabial folds [12]. Coalescence of lesions may lead to the formation of annular or nonannular plaques [43]. Upon resolution, faintly discolored, occasionally atrophic macules may remain at previous sites of involvement [44].

A rare, micropapular variant consists of small, 1 to 2 mm, flesh-colored to faintly erythematous, nonfollicular, variably pruritic papules that erupt on the trunk, extremities, and/or face [45].

Differential diagnosis – Papular lesions of sarcoidosis may clinically resemble lichen planus, granuloma annulare, granulomatous rosacea, appendageal tumors, xanthelasma, or xanthomas [7]. Infrequently, lesions may resemble lichen nitidus (picture 1A) [46,47].

Plaque sarcoidosis — Plaque sarcoidosis is a common form of cutaneous sarcoidosis that presents with well-demarcated plaques [16].

Clinical features Plaque sarcoidosis often presents with oval or annular, indurated, discrete plaques that are skin colored, erythematous, or brown (picture 1C-D). Occasionally, scale is present. Frequent sites of involvement include the shoulders and arms, back, and buttocks [7].

Less common variants of plaque sarcoidosis are reviewed below. (See 'Angiolupoid sarcoidosis' below and 'Psoriasiform sarcoidosis' below and 'Verrucous sarcoidosis' below.)

Differential diagnosis – Examples of disorders that may clinically resemble plaque sarcoidosis include psoriasis, lichen planus, discoid lupus, granuloma annulare, cutaneous T cell lymphoma, lymphomatoid granulomatosis, Kaposi sarcoma, and secondary syphilis [7]. (See 'Psoriasiform sarcoidosis' below.)

Nodular sarcoidosis — Nodular sarcoidosis is a relatively common form of cutaneous sarcoidosis that results from large collections of sarcoidal granulomas in the dermis or subcutaneous tissue [9,10]. In one series of patients with skin manifestations of sarcoidosis, nodules were present in 10 out of 28 patients (36 percent) [10]. (See 'Subcutaneous sarcoidosis' below.)

Clinical features – Nodules tend to be between 1 and 2 cm in diameter and may be single or multiple. On the nose, nodular sarcoidosis can resemble rosacea-associated rhinophyma (picture 3) [48,49]. (See "Rosacea: Pathogenesis, clinical features, and diagnosis", section on 'Phenotypes'.)

Differential diagnosis – The clinical differential diagnosis includes other types of nodular granulomas, such as foreign body reactions, granuloma annulare, rheumatoid nodules, lymphocytoma cutis, nodular cutaneous primary neoplastic and metastatic lesions, and atypical mycobacterial infections [8].

Subcutaneous sarcoidosis — The terms "subcutaneous sarcoidosis" and "Darier-Roussy sarcoidosis" are used to describe nodular sarcoidosis that primarily involves the subcutaneous tissue (picture 1F) [4].

Estimates of the frequency of subcutaneous lesions in patients with sarcoidosis vary, ranging from 1 to 12 percent [4,50-52]. Based upon data from one retrospective review of 54 patients with subcutaneous sarcoidosis, the disorder may be more common in females and in middle-aged adults and may be associated with a predisposition to autoimmune disease [53]. Although some reports have suggested that subcutaneous sarcoidosis is a marker for an increased risk for systemic disease, the relationship remains controversial [4,51,53,54].

Clinical features – Subcutaneous sarcoidosis presents as erythematous, skin-colored, violaceous, or hyperpigmented nodules. On the forearms, lesions often follow a linear distribution and even coalesce to form bands [53].

Differential diagnosis – Patients with sarcoidosis have an increased risk for the development of erythema nodosum, which can also present with erythematous, tender nodules. The possibility of erythema nodosum should be considered in patients with sarcoidosis who present with nodular lesions, particularly when the nodules are located on the lower legs. In contrast to erythema nodosum, nodules of subcutaneous sarcoidosis predominate on the upper extremities and are not usually or only mildly tender [53]. Biopsy is useful for distinguishing between these diagnoses [53]. (See 'Erythema nodosum' below.)

Other lesions that may resemble subcutaneous sarcoidosis on clinical examination include lipomas, cysts, subcutaneous granuloma annulare, foreign body granulomas, or cutaneous manifestations of lymphoproliferative malignancies [7].

Lupus pernio — Lupus pernio is a distinct form of cutaneous sarcoidosis. Lupus pernio disproportionally affects Black persons and females [55]. The presence of lupus pernio appears to be associated with an increased risk for extracutaneous disease, particularly sarcoidosis involving the respiratory tract [4,6,56-58]. Among 35 patients with lupus pernio in one case series, intrathoracic disease (lymphadenopathy or pulmonary abnormalities), upper respiratory disease, reticuloendothelial involvement, and ocular lesions were present in 74, 54, 54, and 37 percent, respectively [55]. When severe, granulomatous inflammation of the upper respiratory tract can result in airway obstruction [58].

Clinical features Lupus pernio is characterized by violaceous or erythematous, indurated, infiltrative plaques that are primarily distributed on the central face (picture 4A-B), usually the alar rim, nasal tip, and cheeks. Other frequent sites of involvement include the ears and lips. Less commonly, lesions may affect the dorsal hands, fingers, or toes. Of note, not all sarcoidosis lesions on the nose are lupus pernio [58].

Lupus pernio is less responsive to treatment than other sarcoidosis lesions [8]. The skin lesions heal with scarring [59].

Without treatment, the lesions progressively infiltrate and indurate, eventually resulting in erosion into the underlying cartilage and bone, causing considerable destruction and disfigurement [40]. Lytic and cystic bone lesions, especially in the hands and feet, can underly lesions of lupus pernio [56]. Among the 35 patients with lupus pernio in the case series described above, bone cysts were found in 50 percent of the patients who were radiographed, and in one-half of these cases, cysts were present in both the hands and feet [55].

Differential diagnosis Examples of disorders that may resemble lupus pernio include cutaneous lupus erythematosus, lupus vulgaris, tuberculoid leprosy, and cutaneous benign or malignant lymphocytic infiltrates [60,61].

Hypopigmented sarcoidosis — Hypopigmented sarcoidosis is an uncommon clinical manifestation of sarcoidosis that is most prominent in individuals with highly pigmented skin [16].

Clinical features – Lesions manifest as hypopigmented, well-demarcated, round to oval macules, patches, or barely raised plaques (picture 1I, 1L) [12,62]. Skin-colored or erythematous papules can be found in the center of some lesions of hypopigmented sarcoidosis, leading to an appearance that resembles a fried egg.

Differential diagnosis – Examples of disorders with clinical findings that may resemble hypopigmented sarcoidosis include pityriasis lichenoides chronica, tinea versicolor, hypopigmented mycosis fungoides, leprosy, and vitiligo [63].

Atrophic and ulcerative sarcoidosis — Atrophic sarcoidosis is a form of plaque sarcoidosis that presents with depressed, rather than elevated, plaques. Ulceration may accompany the clinical findings. The term "ulcerative-atrophic sarcoidosis" may be used to describe lesions that are both atrophic and ulcerated (picture 1H) [64].

Ulcerative-atrophic lesions occur in a minority of patients with sarcoidosis. In one retrospective series, ulcerative-atrophic sarcoidosis was detected in 7 out of 147 cases of cutaneous sarcoidosis (5 percent) [65]. All patients with ulcerative-atrophic lesions presented with other mucocutaneous manifestations of sarcoidosis, and the majority also had internal disease. Ulcerative sarcoidosis may be more common in female patients and Black patients than in other populations [64,65].

Lesions of atrophic sarcoidosis may share features with morphea. In addition, atrophic sarcoidosis can share clinical features with necrobiosis lipoidica or lipodermatosclerosis; these variants often ulcerate. Similar to other specific lesions of sarcoidosis, histopathologic examination of atrophic types of sarcoidosis reveals noncaseating granulomas.

Morpheaform In the morpheaform variant, lesions begin as firm, sclerotic, flesh-colored or hyperpigmented plaques that evolve into depressed lesions over time [7]. The lesions occur more frequently on the lower extremities than on the upper extremities [66]. Histopathologic examination of the dermis reveals markedly thickened collagen bundles and obliteration of the subcutaneous tissue. Rarely, lesions occur in a linear distribution, a clinical presentation that closely resembles linear morphea [67].

Necrobiosis lipoidica-like In a rare subtype of atrophic sarcoidosis, the necrobiosis lipoidica variant, pink to violaceous plaques with depressed centers develop on the shins. Necrobiotic changes in collagen bundles surrounded by epithelioid histiocytes and foreign-body giant cells are present histologically.

Lipodermatosclerosis-like Lipodermatosclerosis-like atrophic sarcoidosis presents on the lower extremities as brown, indurated, circumferential, progressively fibrotic plaques. This variant of sarcoidosis should be considered in cases of lipodermatosclerosis (sclerosing panniculitis) that do not respond to compression and standard treatments. A feature that favors sarcoidosis is a unilateral distribution [68].

Rare variants — Angiolupoid, psoriasiform, and verrucous sarcoidosis are rare variants of plaque sarcoidosis. Ichthyosiform and erythrodermic sarcoidosis are additional uncommon variants that present with extensive cutaneous involvement [40].

Angiolupoid sarcoidosis — Angiolupoid sarcoidosis (also called Brocq-Pautrier angiolupoid) is a variant of plaque sarcoidosis characterized by the presence of prominent, large telangiectasias. Usually a single minimally raised plaque develops on the central face, ears, or scalp; females are most frequently affected (picture 1J, 1M) [69]. The center of the lesion may be relatively lighter in color than the periphery, and in some cases, the plaque may possess an annular configuration. Angiolupoid sarcoidosis may be mistaken for rosacea or a large basal cell carcinoma.

Psoriasiform sarcoidosis — Psoriasiform sarcoidosis is a type of plaque sarcoidosis that presents with well-demarcated, erythematous, scaly plaques that may be indistinguishable from psoriasis (picture 5). In contrast to psoriatic lesions, sarcoidal plaques may resolve with scarring or atrophy.

Despite sharing a T helper type 1 (Th1) and T helper type 17 (Th17) pathogenesis, the association of psoriasis with sarcoidosis is rare, with the largest reported series consisting of seven cases. The authors suggested that uveitis may be less common in these patients, but the series is too small for conclusions [70].

Verrucous sarcoidosis — Lesions of verrucous sarcoidosis consist of well-demarcated, exophytic, hyperkeratotic plaques or discrete, papillomatous, skin-colored papules (picture 6) or plaques [71]. Most cases involve the lower extremities. Lesions may resemble warts, prurigo nodularis, or hypertrophic lichen planus [71]. Patients usually have systemic involvement, frequently manifesting as significant pulmonary disease [72].

Disseminated lichenoid sarcoidosis — Disseminated lichenoid sarcoidosis is a very rare type characterized by multiple discrete, miliary and lichenoid papules over patches of erythema in a distribution that may be so widespread as to resemble erythroderma [73].

Ichthyosiform sarcoidosis — The findings of ichthyosiform sarcoidosis consist of adherent, irregular, polygonal, dry, gray or brown scales varying in size from 0.1 to 1 cm. The most common sites of involvement are the lower extremities, especially the pretibial area (picture 7) [74].

The skin lesions usually appear concurrently with or precede the diagnosis of systemic sarcoidosis but may also occur in the setting of established systemic disease [75]. It is estimated that 95 percent of patients eventually develop systemic involvement [56]. In a literature review that identified reports of 34 patients with ichthyosiform sarcoidosis, 31 patients (91 percent) had extracutaneous involvement, with the most common sites being the lungs (66 percent), lymph nodes (57 percent), and eyes (31 percent) [74].

The patient's history and the detection of dermal noncaseating granulomas in a biopsy specimen from affected tissue distinguish sarcoidal ichthyosis from other forms of ichthyosis [76]. Rarely, sarcoidosis manifests as ichthyosiform erythroderma, with sudden development of diffuse erythema and ichthyotic scale [77]. (See 'Erythrodermic sarcoidosis' below.)

The detection of a diminished stratum corneum and hyperkeratosis, in addition to sarcoidal granulomas, helps to establish the diagnosis of this variant. In the literature review that included 34 patients with ichthyosiform sarcoidosis, a diminished stratum corneum and hyperkeratosis were identified in 63 and 51 percent of patients, respectively [74].

Erythrodermic sarcoidosis — Erythrodermic sarcoidosis typically begins with slightly infiltrated, erythematous to yellow-brown plaques that subsequently coalesce over large areas of the skin (picture 8A-B) [78-81]. Desquamation is common. In contrast to classic exfoliative erythroderma, some areas of skin are usually spared. Patients with erythrodermic sarcoidosis may have symptoms or signs of concomitant systemic involvement, such as fever, weight loss, arthralgias, uveitis, and dyspnea [79].

The absence of large, thick, polygonal scales differentiates erythrodermic sarcoidosis from nonsarcoidal ichthyosiform erythroderma. The course of the disease is variable. Histopathologic evaluation is necessary to exclude more common causes of erythroderma, such as psoriasis, eczema, drug eruptions, and cutaneous T cell lymphoma [82].

Perforating sarcoidosis — The typical cutaneous manifestations of perforating sarcoidosis are papules with keratotic plug [83]. However, transepithelial elimination, a characteristic histopathologic finding of perforating disorders, has been reported in other types of lesions, such as facial papules. In one report, the presence of transepithelial elimination in scaly, pruritic, pubic papules and atrophic, vulvar patches resembling lichen sclerosus prompted the authors to examine previous biopsies of cutaneous sarcoidosis cases [84]. They found that transepithelial elimination, defined as "epithelial channel formation with a sarcoidal-type granuloma completely surrounded by squamous epithelium," was present in 9 of 50 (18 percent) of their skin sarcoidosis cases.

Other — Other rare forms of cutaneous sarcoidosis reported in the literature include pustular sarcoidosis and a photodistributed form of sarcoidosis [12,85-87]. It is unclear whether photodistributed sarcoidosis is a true entity or whether lesions actually represent the granulomatous variant of rosacea.

In addition, it remains to be seen whether syringotropic sarcoidosis, cutaneous sarcoidosis histologically characterized by granulomas surrounding eccrine glands, is a distinct clinical variant. Syringotropic sarcoidosis was reported in three female patients who presented with erythematous patches and plaques on the lower extremities (resembling asteatotic eczema) and localized hypohidrosis [88]. Anhidrosis may also occur as a feature of systemic sarcoidosis due to sarcoidosis-associated autonomic dysfunction [89].

Special sites — Several presentations of specific lesions of sarcoidosis have been described based upon the sites of lesion development. Examples include scar, tattoo, hair/scalp, nail, genital, and oral areas.

Scar sarcoidosis — The presence of sarcoidal granulomas in scar tissue is a relatively common manifestation of cutaneous sarcoidosis [9]. In one series of 170 patients with cutaneous sarcoidosis, 15 patients (9 percent) presented with disease involving scars [9].

Scars from surgical incisions, venipuncture, acne, pseudofolliculitis barbae, herpes zoster virus, and other forms of skin trauma are potential sites for the development of lesions [90-92]. Affected scars thicken and occasionally become erythematous or violaceous. Lesions are often asymptomatic, but some patients may note a sensation of irritation.

Scar sarcoidosis can occur as early as six months to as long as 59 years after an injury [93]. Scar sarcoidosis can also appear acutely in patients with Löfgren syndrome. (See "Sarcoid arthropathy".)

Scar sarcoidosis may be more common than recognized since some lesions may be misdiagnosed as hypertrophic scars or keloids. Like sarcoidosis, keloids respond to intralesional corticosteroid therapy.

Koebnerization (the appearance of skin disease at sites of skin injury) may be a factor in some cases of scar or tattoo sarcoidosis. The development of erythematous sarcoidosis papules along veins on sites previously injected with narcotics has been reported [94].

The relationship between scar sarcoidosis and systemic sarcoidosis remains unclear. While some authors have proposed a strong link between scar sarcoidosis and systemic disease [95,96], others have commented on a more benign nature and good prognosis in patients who present with isolated scar sarcoidosis [7,97].

Tattoo sarcoidosis — Sarcoidal granulomas can develop in tattoos and may be the initial presentation of sarcoidosis in some patients. Tattoo sarcoidosis can occur within one year of tattoo placement or may develop decades after the tattoo was obtained [98]. Although red ink (cinnabar) tattoos are most commonly affected, sarcoidal infiltration in tattoos created with other pigments can also occur. The development of sarcoidal granulomas in tattoos of the eyebrows and lips has also been reported [98].

Affected tattoos develop papules within them or become raised, firm, and edematous (picture 1G). Patients may experience pain or pruritus at sites of involvement.

Histopathologic examination reveals the presence of sarcoidal granulomas showing aggregates of epithelioid cells surrounded by peripheral rings of lymphocytes [98]. The histopathologic differential diagnosis includes foreign body reactions to tattoo pigment, which also present with granulomatous infiltrates in the dermis.

Since sarcoidal tattoo reactions can be the presenting signs of sarcoidosis, patients who present with these lesions should be evaluated for systemic disease. In one retrospective case series of 19 patients with scar sarcoidosis, hilar adenopathy, uveitis, arthritis, or pulmonary disease were present in 74, 21, 16, and 16 percent, respectively [98].

Alopecia — Hair loss is an uncommon specific manifestation of sarcoidosis. Sarcoidal alopecia is primarily seen on the scalp but may be seen in other areas, such as the face [99]. Alopecia may be scarring or nonscarring.

Scalp sarcoidosis — Lesions on the scalp typically present as localized atrophic, annular, or indurated plaques or skin-colored or erythematous nodules (picture 9). Associated hair loss depends on the degree of sarcoidal involvement of the hair follicles and is not always present. Scale is usually absent but may be seen in some cases [100,101]. If scalp disease progresses, local destruction and scarring of hair follicles leads to the development of permanent alopecia that is indistinguishable from pseudopelade of Brocq. In some cases, scalp involvement may become extensive, leading to significant hair loss [100].

Follicular plugging, as seen in discoid lupus erythematosus, may also be present in patients with alopecia secondary to sarcoidosis [102]. The presence of orange spots on trichoscopy has been reported as a possible diagnostic clue for sarcoidosis [103].

Nail sarcoidosis — Sarcoidosis involving the fingers or toes can produce a wide variety of nail plate changes [104], such as thinning, brittleness, pitting, thickening, transverse layering (nail splitting), increased convexity, onycholysis [105], subungual hyperkeratosis [106], clubbing, pseudoclubbing, paronychia with nail fold fissuring, pterygium [107], longitudinal ridging [108], splinter hemorrhages [109], and red or brown discoloration of the nail bed [110,111]. Disease progression can eventually result in pterygium formation (adherence of the proximal nail fold to the nail bed) and total loss of the nail (anonychia).

Granulomatous infiltration of the nail matrix and compression by sarcoidal granulomas on nail structures may contribute to the appearance of nail dystrophy. Sarcoidal nail plate dystrophy is often accompanied by phalangeal bone disease.

The combination of nail disease and bone involvement can occur in sarcoidal dactylitis, a variant of sarcoidosis that presents with bilateral fusiform or sausage-shaped swellings of the fingers (picture 10) [52]. Radiographic examination of affected digits reveals erosions in the distal phalanges. "Drumstick dactylitis," a rare severe form of sarcoidal dactylitis characterized by bulbous swelling of the fingertips, has been associated with lupus pernio [54]. (See 'Lupus pernio' above.)

Genital sarcoidosis — There have been only a few reports of vulvar sarcoidosis, which can present with papules, plaques, or nodules [112-114]. Sarcoidosis of the male genitalia may present as indurated papules, painful nodules with or without ulceration, or swelling of the scrotum or penis [115-119].

Sarcoidosis of the oral cavity — Sarcoidosis involving the oral cavity is rare, with less than 70 reported cases. Presentations include papules; papulonodules; edema; ulcers; or gingival abnormalities, such as gingivitis, gingival hyperplasia, or gingival recession (picture 11) [120-123]. In a review of 47 cases of sarcoidal involvement of the soft tissues of the oral cavity, nodules and localized swelling were the most frequent manifestations of mucosal disease, occurring in 34 patients (72 percent) [120]. In the soft tissues of the oral cavity, the most commonly affected site was the buccal mucosa (28 percent), followed by the gingiva (22 percent), lips (13 percent), floor of the mouth or sublingual glands (11 percent), tongue (11 percent), palate (6 percent), and submandibular gland (4 percent) [120].

NONSPECIFIC LESIONS — Erythema nodosum is the most common nonspecific cutaneous manifestation of sarcoidosis.

Erythema nodosum — Erythema nodosum develops in up to 25 percent of patients with sarcoidosis and is clinically and histologically identical to erythema nodosum secondary to other causes [11]. Sarcoidosis is a relatively common cause of erythema nodosum; in a Spanish study of 106 biopsy-proven cases of erythema nodosum, 20 percent of patients had sarcoidosis [124].

Clinical features – Patients with erythema nodosum develop erythematous, tender, subcutaneous plaques and nodules predominantly located on the anterior tibial areas (picture 12A-B) [43]. Arthritis, lower extremity edema, and low-grade fever are the most common systemic symptoms associated with erythema nodosum. (See "Erythema nodosum".)

Erythema nodosum is a transient disorder. In a case series that included 251 patients with sarcoidosis-associated erythema nodosum, over 85 percent had complete resolution within two years [125]. In addition, erythema nodosum has been associated with a favorable prognosis for sarcoidosis [125,126].

Löfgren syndrome is an acute presentation of sarcoidosis characterized by the triad of hilar adenopathy, erythema nodosum, and polyarthralgia or arthritis, with or without parenchymal infiltrates or fever [127-129]. (See "Sarcoid arthropathy", section on 'Acute arthritis and Lofgren syndrome'.)

Differential diagnosis – The clinical features of subcutaneous sarcoidosis can resemble erythema nodosum [130]. Biopsy is useful for distinguishing between these disorders. Histopathologic findings in erythema nodosum are consistent with a septal panniculitis. Additional disorders in the differential diagnosis of erythema nodosum are reviewed separately. (See "Erythema nodosum", section on 'Differential diagnosis'.)

The presence of bilateral hilar adenopathy and erythema nodosum is usually, but not always, caused by acute sarcoidosis. This presentation has also been reported in tuberculosis, lymphoma, streptococcal infection, histoplasmosis, coccidiomycosis, and Chlamydia pneumoniae infection [131,132]. (See "Erythema nodosum".)

Other disorders — Examples of other nonspecific eruptions include calcinosis cutis, erythema multiforme, prurigo, Sweet syndrome, and nail clubbing.

DRUG-INDUCED SARCOIDOSIS-LIKE REACTIONS — Drug-induced sarcoidosis-like reactions (DISR) are clinically and histopathologically indistinguishable from sarcoidosis and occur in temporal relationship with initiation of a drug [133]. Similar to sarcoidosis, DISR can affect various organ systems and can include the development of sarcoid-like, granulomatous skin lesions. Multiple drugs have been associated with DISR. Tumor necrosis factor (TNF)-alpha antagonists (adalimumab, etanercept, infliximab), interferons, and immune checkpoint inhibitors (ipilimumab, nivolumab, pembrolizumab, unspecified anti-programmed death ligand 1 [PD-L1] antibody) are among the most commonly reported contributors [134]. (See "Clinical manifestations and diagnosis of sarcoidosis", section on 'Differential diagnosis'.)

DIAGNOSIS

Approach — The diagnosis of sarcoidosis requires a compatible clinical picture, the demonstration of noncaseating granulomas on tissue biopsy, and the exclusion of other disorders that can present with similar clinical and histopathologic findings [35,135].

Accordingly, a diagnosis of cutaneous sarcoidosis is supported by these findings:

The identification of skin lesions that are morphologically compatible with sarcoidosis

The detection of sarcoidal granulomas on histopathologic examination

The exclusion of other disorders in the differential diagnosis

The initial diagnostic work-up includes a physical examination and skin biopsy. In some cases, sarcoidosis may be suspected based upon the physical examination; however, given the wide variety of clinical presentations of sarcoidosis, the diagnosis is not always suspected prior to the results of histopathologic examination.

When physical examination and biopsy findings consistent with sarcoidosis are identified in a patient without a known history of the disease, an assessment for signs of extracutaneous sarcoidosis is indicated. This typically includes a review of systems, complete physical examination, chest radiography, and additional tests. Given the accessibility of the skin and ease of skin biopsy, recognition of lesions of cutaneous sarcoidosis can be highly valuable in patients with symptoms or radiologic findings that are suggestive of systemic disease, as they may prevent the need for a more invasive tissue biopsy in some patients. (See 'Evaluation for systemic disease' below and "Clinical manifestations and diagnosis of sarcoidosis", section on 'Patients without accessible extrathoracic disease'.)

Whether sarcoidosis can be diagnosed when there are cutaneous findings consistent with sarcoidosis but no other signs of sarcoidosis is controversial [16]. In 1999, a joint statement from three expert societies indicated that the detection of noncaseating granulomas in the skin was not sufficient to confirm a diagnosis of sarcoidosis in the absence of evidence for other organ involvement [135]. However, others, including ourselves, support the existence of isolated cutaneous sarcoidosis [136].

Physical examination — An examination of the skin is the first step towards confirming a diagnosis of cutaneous sarcoidosis. Although there are no physical features that confirm a diagnosis of cutaneous sarcoidosis, clinician familiarity with potential manifestations of sarcoidosis is helpful for identifying patients who may benefit from a skin biopsy to assess for sarcoidosis. (See 'Specific lesions' above.)

Additional examination techniques that can support clinical suspicion for sarcoidosis include diascopy and dermoscopy.

Diascopy – Diascopy, a procedure that involves compressing a skin lesion with a clear glass microscope slide, is a simple method for detecting cutaneous granulomatous disorders on clinical examination. In granulomatous conditions, diascopy often reveals a subtle, brown-yellow or "apple jelly" color during lesion compression. This sign is most appreciable in individuals with light skin pigmentation. Diascopy is not a specific test for sarcoidosis, and other granulomatous disorders can exhibit similar findings.

Dermoscopy – Dermatoscopic evaluation is also not a specific diagnostic technique for cutaneous sarcoidosis, as similar findings may occur in other granulomatous lesions. The typical findings include translucent, round or ovoid, yellowish or reddish-orange, focally or diffusely distributed globules. Common vascular features include linear vessels, branching vessels, or arborizing vessels; less common vascular findings are glomerular or dotted structures [137] and whitish, structureless areas on a yellow-orange background.

Reflectance confocal microscopy – Although not typically performed in the clinical setting, reflectance confocal microscopic examination may demonstrate roundish structures, corresponding to granulomas with giant multinucleated cells inside characterized by a dark nuclei surrounded by a highly hyper-refractile cytoplasm [138]. These findings do not differentiate between sarcoidosis and other granulomatous lesions.

Skin biopsy — In lesions that are clinically suspicious for sarcoidosis, a skin biopsy should be performed. Ideally, biopsies should include the full thickness of the dermis and at least the superficial portion of the subcutaneous tissue; a punch biopsy or incisional biopsy is generally sufficient. (See "Skin biopsy techniques", section on 'Punch biopsy'.)

Although noncaseating granulomas with sparse peripheral lymphocytic infiltrates are characteristic of sarcoidosis, similar histopathologic features may be seen in other disorders, and not all lesions of sarcoidosis demonstrate classic findings [139]. (See 'Histopathology' above.)

Biopsy specimens should be examined under polarized light to evaluate for the presence of refractile material that could indicate granuloma formation secondary to a foreign body reaction. In addition, tissue staining for acid-fast bacilli and fungi, microbial cultures of fresh tissue, and tuberculin skin testing should be performed if clinical or histopathologic features suggest the possibility of mycobacterial or deep fungal infections [23,96,140].

Evaluation for systemic disease — In the patient presenting with cutaneous lesions that are clinically and histopathologically consistent with sarcoidosis, the following work-up for systemic disease should be performed [141-143]:

Focused patient history and review of systems

Complete physical examination

Posterior and anterior chest radiography

Pulmonary function tests including diffusing capacity studies (see "Overview of pulmonary function testing in adults" and "Overview of pulmonary function testing in children")

Electrocardiogram

Ophthalmologic examination

Laboratory studies (complete blood count [CBC], serum calcium, hepatic transaminases, alkaline phosphatase, blood urea nitrogen [BUN], serum creatinine, urinalysis)

Tuberculin skin test or interferon-gamma release assay for latent tuberculosis (to assist with identifying patients who may have tuberculosis rather than sarcoidosis) (see "Use of interferon-gamma release assays for diagnosis of tuberculosis infection (tuberculosis screening) in adults" and "Tuberculosis infection (latent tuberculosis) in adults: Approach to diagnosis (screening)")

Invasive diagnostic tests, such as intrathoracic lymph node biopsies, are also utilized for the recognition of extracutaneous sarcoidosis but are not necessary for all patients. Indications for invasive diagnostic testing are reviewed separately. (See "Clinical manifestations and diagnosis of sarcoidosis", section on 'Invasive diagnostic testing'.)

Other tests — Other tests that are not indicated for the diagnosis of sarcoidosis but have been used in the evaluation of sarcoidosis include angiotensin-converting enzyme (ACE) level; other serum markers of sarcoidosis; and historically, the intradermal (Kveim-Siltzbach) test. (See "Clinical manifestations and diagnosis of sarcoidosis", section on 'Proposed activity tests, including angiotensin converting enzyme (ACE) level'.)

ACE level – Measurement of serum angiotensin-converting enzyme (ACE) level is sometimes considered in patients who present with signs or symptoms suggestive of sarcoidosis. However, ACE levels are nonspecific for the diagnosis of sarcoidosis [7]. ACE levels are sometimes used for following the response to treatment in patients with systemic sarcoidosis; the value of the test for this indication remains unclear.

Other serologic studies – Other markers, such as serum lysozyme, neopterin, soluble interleukin (IL) 2 receptor, and osteopontin, that can be elevated in the presence of granulomatous disease are even less specific than ACE levels for the diagnosis of sarcoidosis and are unlikely to be elevated in patients in whom the disease burden is limited to the skin [144]. In a targeted evaluation of primers associated with sarcoidosis in ribonucleic acid (RNA) from paraffin-embedded sarcoidal tissue (most from lymph nodes), T-bet messenger ribonucleic acid (mRNA) expression was the only marker significantly greater in sarcoid granulomas than both suture granulomas and fungal granulomas [145]. Laboratory abnormalities, such as leukopenia, anemia, eosinophilia, and hypercalcemia, are rare in the absence of systemic disease.

Kveim-Siltzbach test – Historically, the Kveim-Siltzbach test was used in the diagnosis of sarcoidosis [59]. The test involves the injection of spleen extract from an individual with systemic sarcoidosis into the dermis of patients with signs or symptoms suggestive of sarcoidosis. The injection site is subsequently biopsied to assess for the formation of granulomas. In one series of 127 patients with cutaneous sarcoidosis, 38 percent had a positive Kveim test six weeks after injection [59].

Due to poor standardization of the test, concern about transfer of viral infections, and unavailability of the substrate in many countries, the Kveim-Siltzbach test is rarely performed in the clinical setting.

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Sarcoidosis".)

INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5th to 6th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10th to 12th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.

Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)

Basics topic (see "Patient education: Erythema nodosum (The Basics)")

SUMMARY AND RECOMMENDATIONS

Disease overview – Sarcoidosis is a granulomatous disease that can affect various organs, such as the lung, heart, neurologic system, gastrointestinal tract, skin, bone, and joints. The presence of noncaseating granulomas in organs and tissue is a classic feature. Cutaneous involvement is estimated to occur in approximately 25 percent of patients and has a wide variety of clinical manifestations. (See 'Introduction' above and "Clinical manifestations and diagnosis of sarcoidosis".)

Pathogenesis – The pathogenesis of cutaneous sarcoidosis is not well understood. A combination of genetic and environmental factors may contribute to an aberrant immune response and granuloma formation. (See 'Pathogenesis' above and "Pathology and pathogenesis of sarcoidosis".)

Clinical manifestations – The cutaneous manifestations of sarcoidosis may be divided into specific and nonspecific lesions. Specific lesions of sarcoidosis classically demonstrate noncaseating granulomas with sparse peripheral lymphocytic infiltrates on biopsy. Nonspecific lesions are cutaneous disorders that are associated with sarcoidosis but do not demonstrate these histopathologic features. (See 'Classification' above.)

Specific lesions – The morphology of specific cutaneous lesions of sarcoidosis varies widely. Examples of clinical manifestations include papules; nodules; plaques; and hypopigmented, atrophic, or ulcerative lesions (picture 1A-J). Several rare variants may closely resemble other cutaneous diseases. Presentations of sarcoidosis in particular sites have also been described, such as scar tissue, tattoos, scalp skin, genital skin, nail, and oral cavity. (See 'Specific lesions' above and 'Rare variants' above and 'Special sites' above.)

Lupus pernio is a distinct variant of cutaneous sarcoidosis that presents with violaceous or erythematous papules, plaques, or nodules predominantly involving the central facial skin (picture 4A-B). The nasal alae are often affected. Patients with lupus pernio appear to have an increased risk for respiratory tract sarcoidosis. (See 'Lupus pernio' above.)

Nonspecific lesions – Erythema nodosum, a form of panniculitis, is the most common nonspecific manifestation of sarcoidosis. Patients usually present with inflammatory plaques or nodules on the lower legs. A skin biopsy is useful for distinguishing erythema nodosum from subcutaneous sarcoidosis. Examples of other nonspecific eruptions include calcinosis cutis, erythema multiforme, prurigo, Sweet syndrome, and nail clubbing. (See 'Erythema nodosum' above and 'Nonspecific lesions' above.)

Diagnosis – The diagnosis of cutaneous sarcoidosis involves a physical examination that identifies skin lesions that are morphologically compatible with sarcoidosis, a skin biopsy that demonstrates sarcoidal granulomas on histopathologic examination, and the exclusion of other disorders in the differential diagnosis.

The differential diagnosis of cutaneous sarcoidosis is broad and includes multiple infectious and noninfectious disorders that may exhibit cutaneous granulomas. The specific clinical findings guide the differential diagnosis. Examples of disorders that are often in the differential diagnosis include deep fungal infections, tuberculosis, nontuberculous mycobacterial infections, and foreign body reactions. Special histopathologic stains and fresh tissue cultures can be helpful for identifying infection. Histopathologic examination under polarized light can aid with the detection of foreign bodies in the skin. (See 'Histopathology' above and 'Differential diagnosis' above.)

Evaluation for systemic disease – Patients with cutaneous sarcoidosis should be evaluated for extracutaneous involvement. Testing should include a complete physical examination, chest radiograph, pulmonary function test, electrocardiogram, tuberculin skin testing, a urinalysis, and several blood studies. (See 'Evaluation for systemic disease' above.)

  1. Hanno R, Needelman A, Eiferman RA, Callen JP. Cutaneous sarcoidal granulomas and the development of systemic sarcoidosis. Arch Dermatol 1981; 117:203.
  2. English JC 3rd, Patel PJ, Greer KE. Sarcoidosis. J Am Acad Dermatol 2001; 44:725.
  3. Samtsov AV. Cutaneous sarcoidosis. Int J Dermatol 1992; 31:385.
  4. Mangas C, Fernández-Figueras MT, Fité E, et al. Clinical spectrum and histological analysis of 32 cases of specific cutaneous sarcoidosis. J Cutan Pathol 2006; 33:772.
  5. Elgart MD. Skin manifestations of sarcoidosis. Cutis 1965; 1:283.
  6. Marcoval J, Mañá J, Rubio M. Specific cutaneous lesions in patients with systemic sarcoidosis: relationship to severity and chronicity of disease. Clin Exp Dermatol 2011; 36:739.
  7. Lodha S, Sanchez M, Prystowsky S. Sarcoidosis of the skin: a review for the pulmonologist. Chest 2009; 136:583.
  8. Sanchez M, Haimovic A, Prystowsky S. Sarcoidosis. Dermatol Clin 2015; 33:389.
  9. Yanardağ H, Pamuk ON, Karayel T. Cutaneous involvement in sarcoidosis: analysis of the features in 170 patients. Respir Med 2003; 97:978.
  10. Ben Jennet S, Benmously R, Chaâbane S, et al. [Cutaneous sarcoidosis through a hospital series of 28 cases]. Tunis Med 2008; 86:447.
  11. Lynch PJ, Sams WM Jr. Principles and Practice of Dermatology, Churchill Livingstone Inc, 1996.
  12. Elgart ML. Cutaneous sarcoidosis: definitions and types of lesions. Clin Dermatol 1986; 4:35.
  13. Arkema EV, Cozier YC. Sarcoidosis epidemiology: recent estimates of incidence, prevalence and risk factors. Curr Opin Pulm Med 2020; 26:527.
  14. Lundkvist A, Kullberg S, Arkema EV, et al. Differences in disease presentation between men and women with sarcoidosis: A cohort study. Respir Med 2022; 191:106688.
  15. James DG, Kendig EL Jr. Childhood sarcoidosis. Sarcoidosis 1988; 5:57.
  16. Ezeh N, Caplan A, Rosenbach M, Imadojemu S. Cutaneous Sarcoidosis. Dermatol Clin 2023; 41:455.
  17. Kassamali B, Villa-Ruiz C, Kus KJB, et al. Increased risk of systemic and cardiac sarcoidosis in Black patients with cutaneous sarcoidosis. J Am Acad Dermatol 2022; 86:1178.
  18. Zaba LC, Smith GP, Sanchez M, Prystowsky SD. Dendritic cells in the pathogenesis of sarcoidosis. Am J Respir Cell Mol Biol 2010; 42:32.
  19. Ali MM, Atwan AA, Gonzalez ML. Cutaneous sarcoidosis: updates in the pathogenesis. J Eur Acad Dermatol Venereol 2010; 24:747.
  20. Kim YC, Triffet MK, Gibson LE. Foreign bodies in sarcoidosis. Am J Dermatopathol 2000; 22:408.
  21. Derler AM, Eisendle K, Baltaci M, et al. High prevalence of 'Borrelia-like' organisms in skin biopsies of sarcoidosis patients from Western Austria. J Cutan Pathol 2009; 36:1262.
  22. Lassalle S, Selva E, Hofman V, et al. Sarcoid-like lesions associated with the immune restoration inflammatory syndrome in AIDS: absence of polymerase chain reaction detection of Mycobacterium tuberculosis in granulomas isolated by laser capture microdissection. Virchows Arch 2006; 449:689.
  23. Ball NJ, Kho GT, Martinka M. The histologic spectrum of cutaneous sarcoidosis: a study of twenty-eight cases. J Cutan Pathol 2004; 31:160.
  24. Marcoval J, Mañá J, Moreno A, et al. Foreign bodies in granulomatous cutaneous lesions of patients with systemic sarcoidosis. Arch Dermatol 2001; 137:427.
  25. Walsh NM, Hanly JG, Tremaine R, Murray S. Cutaneous sarcoidosis and foreign bodies. Am J Dermatopathol 1993; 15:203.
  26. Batres E, Klima M, Tschen J. Transepithelial elimination in cutaneous sarcoidosis. J Cutan Pathol 1982; 9:50.
  27. Callen JP. The presence of foreign bodies does not exclude the diagnosis of sarcoidosis. Arch Dermatol 2001; 137:485.
  28. Alexis JB. Sarcoidosis presenting as cutaneous hypopigmentation with repeatedly negative skin biopsies. Int J Dermatol 1994; 33:44.
  29. Shirodaria CC, Nicholson AG, Hansell DM, et al. Lesson of the month: Necrotizing sarcoid granulomatosis with skin involvement. Histopathology 2003; 43:91.
  30. Rosen Y, Moon S, Huang CT, et al. Granulomatous pulmonary angiitis in sarcoidosis. Arch Pathol Lab Med 1977; 101:170.
  31. Magro CM, Crowson AN, Regauer S. Granuloma annulare and necrobiosis lipoidica tissue reactions as a manifestation of systemic disease. Hum Pathol 1996; 27:50.
  32. Goldberg LJ, Goldberg N, Abrahams I, et al. Giant cell lichenoid dermatitis: a possible manifestation of sarcoidosis. J Cutan Pathol 1994; 21:47.
  33. Cardoso JC, Cravo M, Reis JP, Tellechea O. Cutaneous sarcoidosis: a histopathological study. J Eur Acad Dermatol Venereol 2009; 23:678.
  34. Esteves TC, Aparicio G, Ferrer B, Garcia-Patos V. Prognostic value of skin lesions in sarcoidosis: clinical and histopathological clues. Eur J Dermatol 2015; 25:556.
  35. Crouser ED, Maier LA, Wilson KC, et al. Diagnosis and Detection of Sarcoidosis. An Official American Thoracic Society Clinical Practice Guideline. Am J Respir Crit Care Med 2020; 201:e26.
  36. Terushkin V, Stern BJ, Judson MA, et al. Neurosarcoidosis: presentations and management. Neurologist 2010; 16:2.
  37. Kim JS, Judson MA, Donnino R, et al. Cardiac sarcoidosis. Am Heart J 2009; 157:9.
  38. García-Colmenero L, Sánchez-Schmidt JM, Barranco C, Pujol RM. The natural history of cutaneous sarcoidosis. Clinical spectrum and histological analysis of 40 cases. Int J Dermatol 2019; 58:178.
  39. Byrne B, Goh A, Izham NF, et al. Systemic evaluation of cutaneous sarcoidosis: 15-year dermatology experience at University Hospital Limerick. Clin Exp Dermatol 2022; 47:850.
  40. Haimovic A, Sanchez M, Judson MA, Prystowsky S. Sarcoidosis: a comprehensive review and update for the dermatologist: part I. Cutaneous disease. J Am Acad Dermatol 2012; 66:699.e1.
  41. Hetherington S. Sarcoidosis in young children. Am J Dis Child 1982; 136:13.
  42. Milman N, Hoffmann AL. Childhood sarcoidosis: long-term follow-up. Eur Respir J 2008; 31:592.
  43. Katta R. Cutaneous sarcoidosis: a dermatologic masquerader. Am Fam Physician 2002; 65:1581.
  44. Mahajan VK, Sharma NL, Sharma RC, Sharma VC. Cutaneous sarcoidosis: clinical profile of 23 Indian patients. Indian J Dermatol Venereol Leprol 2007; 73:16.
  45. Labadie JG, Florek AG, VandenBoom T, et al. Micropapular Cutaneous Sarcoidosis Reviewed. Dermatology 2018; 234:220.
  46. Okamoto H, Horio T, Izumi T. Micropapular sarcoidosis simulating lichen nitidus. Dermatologica 1985; 170:253.
  47. Beacham BE, Schuldenfrei J, Julka SS. Sarcoidosis presenting with erythema multiforme-like cutaneous lesions. Cutis 1984; 33:461.
  48. Dumitrescu SM, Schwartz RA, Baredes S, et al. Mutilating facial sarcoidosis. Dermatology 1999; 199:265.
  49. Leonard AL. A case of sarcoidosis mimicking rhinophyma. J Drugs Dermatol 2003; 2:333.
  50. MAYOCK RL, BERTRAND P, MORRISON CE, SCOTT JH. MANIFESTATIONS OF SARCOIDOSIS. ANALYSIS OF 145 PATIENTS, WITH A REVIEW OF NINE SERIES SELECTED FROM THE LITERATURE. Am J Med 1963; 35:67.
  51. Vainsencher D, Winkelmann RK. Subcutaneous sarcoidosis. Arch Dermatol 1984; 120:1028.
  52. Rodriguez-Gomez M, Fernandez-Sueiro JL, Willisch A, et al. Multifocal dactylitis as the sole clinical expression of sarcoidosis. J Rheumatol 2000; 27:245.
  53. Ahmed I, Harshad SR. Subcutaneous sarcoidosis: is it a specific subset of cutaneous sarcoidosis frequently associated with systemic disease? J Am Acad Dermatol 2006; 54:55.
  54. Jacyk WK. Cutaneous sarcoidosis in black South Africans. Int J Dermatol 1999; 38:841.
  55. Spiteri MA, Matthey F, Gordon T, et al. Lupus pernio: a clinico-radiological study of thirty-five cases. Br J Dermatol 1985; 112:315.
  56. Young RJ 3rd, Gilson RT, Yanase D, Elston DM. Cutaneous sarcoidosis. Int J Dermatol 2001; 40:249.
  57. Aubart FC, Ouayoun M, Brauner M, et al. Sinonasal involvement in sarcoidosis: a case-control study of 20 patients. Medicine (Baltimore) 2006; 85:365.
  58. Jorizzo JL, Koufman JA, Thompson JN, et al. Sarcoidosis of the upper respiratory tract in patients with nasal rim lesions: a pilot study. J Am Acad Dermatol 1990; 22:439.
  59. Veien NK, Stahl D, Brodthagen H. Cutaneous sarcoidosis in Caucasians. J Am Acad Dermatol 1987; 16:534.
  60. Fernandez-Faith E, McDonnell J. Cutaneous sarcoidosis: differential diagnosis. Clin Dermatol 2007; 25:276.
  61. Redissi A, Penmetsa GK, Litaiem N. Lupus pernio. In: StatPearls, StatPearls Publishing, Treasure Island (FL) 2023.
  62. Terunuma A, Watabe A, Kato T, Tagami H. Coexistence of vitiligo and sarcoidosis in a patient with circulating autoantibodies. Int J Dermatol 2000; 39:551.
  63. Sivasaththivel M, Lee S, Gupta S. A Case of hypopigmented sarcoidosis masquerading as Vitiligo in a Caucasian individual. Australas J Dermatol 2022; 63:124.
  64. Albertini JG, Tyler W, Miller OF 3rd. Ulcerative sarcoidosis. Case report and review of the literature. Arch Dermatol 1997; 133:215.
  65. Yoo SS, Mimouni D, Nikolskaia OV, et al. Clinicopathologic features of ulcerative-atrophic sarcoidosis. Int J Dermatol 2004; 43:108.
  66. Burov EA, Kantor GR, Isaac M. Morpheaform sarcoidosis: report of three cases. J Am Acad Dermatol 1998; 39:345.
  67. Hess SP, Agudelo CA, White WL, Jorizzo JL. Ichthyosiform and morpheaform sarcoidosis. Clin Exp Rheumatol 1990; 8:171.
  68. Huang CL, Mutasim DF. Sarcoidosis mimicking lipodermatosclerosis. Cutis 2005; 75:322.
  69. Arias-Santiago S, Fernández-Pugnaire MA, Aneiros-Fernández J, et al. Recurrent telangiectasias on the cheek: angiolupoid sarcoidosis. Am J Med 2010; 123:e7.
  70. Wanat KA, Schaffer A, Richardson V, et al. Sarcoidosis and psoriasis: a case series and review of the literature exploring co-incidence vs coincidence. JAMA Dermatol 2013; 149:848.
  71. Glass LA, Apisarnthanarax P. Verrucous sarcoidosis simulating hypertrophic lichen planus. Int J Dermatol 1989; 28:539.
  72. Ko R, Tanaka M, Murata T, Nishikawa T. Papular fixed drug eruption mimicking folliculitis due to acetominophen. Clin Exp Dermatol 2000; 25:96.
  73. Nishizawa A, Igawa K, Teraki H, Yokozeki H. Diffuse disseminated lichenoid-type cutaneous sarcoidosis mimicking erythroderma. Int J Dermatol 2014; 53:e369.
  74. Chen HW, Vandergriff T. Ichthyosiform sarcoidosis: Report of a case and comprehensive review of the literature. Int J Dermatol 2022; 61:390.
  75. Cather JC, Cohen PR. Ichthyosiform sarcoidosis. J Am Acad Dermatol 1999; 40:862.
  76. Feind-Koopmans AG, Lucker GP, van de Kerkhof PC. Acquired ichthyosiform erythroderma and sarcoidosis. J Am Acad Dermatol 1996; 35:826.
  77. ZHANG H, MA HJ, LIU W, YUAN XY. Sarcoidosis characterized as acquired ichthyosiform erythroderma. Eur J Dermatol 2009; 19:516.
  78. Greer KE, Harman LE Jr, Kayne AL. Unusual cutaneous manifestations of sarcoidosis. South Med J 1977; 70:666.
  79. Wirth FA, Gould WM, Kauffman CL. Erythroderma in a patient with arthralgias, uveitis, and dyspnea. Arch Dermatol 1999; 135:1411, 1414.
  80. Bazex J, Dupin P, Giordano F. [Cutaneous and visceral sarcoidosis. Apropos of an exceptional form]. Ann Dermatol Venereol 1987; 114:685.
  81. Morrison JG. Sarcoidosis in a child, presenting as an erythroderma with keratotic spines and palmar pits. Br J Dermatol 1976; 95:93.
  82. Yoon CH, Lee CW. Case 6. Erythrodermic form of cutaneous sarcoidosis. Clin Exp Dermatol 2003; 28:575.
  83. Hagari Y, Kambe N, Shimao S, et al. Cutaneous sarcoidosis showing multiple papular eruptions with keratotic plugs. J Dermatol 1989; 16:321.
  84. Ismail A, Beckum K, McKay K. Transepithelial elimination in sarcoidosis: a frequent finding. J Cutan Pathol 2014; 41:22.
  85. Truchot F, Skowron F, Grande S, et al. [Photo-induced sarcoidosis]. Ann Dermatol Venereol 2003; 130:40.
  86. Macdonald J, Southgate HJ. Lessons to be learned: a case study approach. Sunshine-induced hypercalcaemia? J R Soc Promot Health 2002; 122:194.
  87. MOSER HS, SOLOWEY CM, LEIDER M. An unusual form of cutaneous sarcoidosis. N Y State J Med 1962; 62:1859.
  88. Hayakawa J, Mizukawa Y, Kurata M, Shiohara T. A syringotropic variant of cutaneous sarcoidosis: presentation of 3 cases exhibiting defective sweating responses. J Am Acad Dermatol 2013; 68:1016.
  89. Nishida M, Namiki T, Sone Y, et al. Acquired anhidrosis associated with systemic sarcoidosis: quantification of nerve fibres around eccrine glands by confocal microscopy. Br J Dermatol 2018; 178:e59.
  90. Norton SA, Chesser RS, Fitzpatrick JE. Scar sarcoidosis in pseudofolliculitis barbae. Mil Med 1991; 156:369.
  91. Cecchi R, Giomi A. Scar sarcoidosis following herpes zoster. J Eur Acad Dermatol Venereol 1999; 12:280.
  92. Kormeili T, Neel V, Moy RL. Cutaneous sarcoidosis at sites of previous laser surgery. Cutis 2004; 73:53.
  93. Payne CM, Thomas RH, Black MM. From silica granuloma to scar sarcoidosis. Clin Exp Dermatol 1983; 8:171.
  94. Buss G, Cattin V, Spring P, et al. Two cases of interferon-alpha-induced sarcoidosis Koebnerized along venous drainage lines: new pathogenic insights and review of the literature of interferon-induced sarcoidosis. Dermatology 2013; 226:289.
  95. JAMES DG. Dermatological aspects of sarcoidosis. Q J Med 1959; 28:108.
  96. Chudomirova K, Velichkova L, Anavi B, Arnaudova M. Recurrent sarcoidosis in skin scars accompanying systemic sarcoidosis. J Eur Acad Dermatol Venereol 2003; 17:360.
  97. Sorabjee JS, Garje R. Reactivation of old scars: inevitably sarcoid. Postgrad Med J 2005; 81:60.
  98. Antonovich DD, Callen JP. Development of sarcoidosis in cosmetic tattoos. Arch Dermatol 2005; 141:869.
  99. Rapp SE. An unusual cause of hair loss. Arch Dermatol 2002; 138:259.
  100. Katta R, Nelson B, Chen D, Roenigk H. Sarcoidosis of the scalp: a case series and review of the literature. J Am Acad Dermatol 2000; 42:690.
  101. Knight L, Ngwanya M. Sarcoidosis of the scalp: the largest single-institutional case series. Int J Dermatol 2019; 58:e149.
  102. Henderson CL, Lafleur L, Sontheimer RD. Sarcoidal alopecia as a mimic of discoid lupus erythematosus. J Am Acad Dermatol 2008; 59:143.
  103. Torres F, Tosti A, Misciali C, Lorenzi S. Trichoscopy as a clue to the diagnosis of scalp sarcoidosis. Int J Dermatol 2011; 50:358.
  104. Mann RJ, Allen BR. Nail dystrophy due to sarcoidosis. Br J Dermatol 1981; 105:599.
  105. Davies MG, McGavin CR. Onycholysis in sarcoidosis--a previously undescribed association. Br J Dermatol 1996; 135:340.
  106. Fujii K, Kanno Y, Ohgo N. Subungual hyperkeratosis due to sarcoidosis. Int J Dermatol 1997; 36:125.
  107. Kalb RE, Grossman ME. Pterygium formation due to sarcoidosis. Arch Dermatol 1985; 121:276.
  108. Aranegui B, Garcia-Cruz A, de la Torre C, González-Valladares MG. Trachyonychia and sarcoidosis. J Am Acad Dermatol 2010; 63:159.
  109. Losada-Campa A, De la Torre-Fraga C, Gomez de Liaño A, Cruces-Prado MJ. Histopathology of nail sarcoidosis. Acta Derm Venereol 1995; 75:404.
  110. Cox NH, Gawkrodger DJ. Nail dystrophy in chronic sarcoidosis. Br J Dermatol 1988; 118:697.
  111. Santoro F, Sloan SB. Nail dystrophy and bony involvement in chronic sarcoidosis. J Am Acad Dermatol 2009; 60:1050.
  112. Ezughah FI, Ghaly AF, Evans A, Green CM. Vulval sarcoid: a systemic presentation of sarcoidosis. J Obstet Gynaecol 2005; 25:730.
  113. Tatnall FM, Barnes HM, Sarkany I. Sarcoidosis of the vulva. Clin Exp Dermatol 1985; 10:384.
  114. de Oliveira Neto MP. [Sarcoidosis with vulvar lesions]. Rev Bras Med 1972; 29:134.
  115. Wei H, Friedman KA, Rudikoff D. Multiple indurated papules on penis and scrotum. J Cutan Med Surg 2000; 4:202.
  116. Mahmood N, Afzal N, Joyce A. Sarcoidosis of the penis. Br J Urol 1997; 80:155.
  117. Rubinstein I, Baum GL, Hiss Y. Sarcoidosis of the penis: report of a case. J Urol 1986; 135:1016.
  118. Vahid B, Weibel S, Nguyen C. Scrotal swelling and sarcoidosis. Am J Med 2006; 119:e3.
  119. HAUSFELD KF. Primary sarcoidosis of the scrotum: case report. J Urol 1961; 86:269.
  120. Suresh L, Radfar L. Oral sarcoidosis: a review of literature. Oral Dis 2005; 11:138.
  121. Blinder D, Yahatom R, Taicher S. Oral manifestations of sarcoidosis. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 1997; 83:458.
  122. Jackowski J, Dragisic D, Arnold G, Dirschka T. Primary oral sarcoidosis preceding Lofgren's syndrome. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2005; 100:183.
  123. Kowalczyk JP, Ricotti CA, de Araujo T, et al. "Strawberry gums" in sarcoidosis. J Am Acad Dermatol 2008; 59:S118.
  124. García-Porrúa C, González-Gay MA, Vázquez-Caruncho M, et al. Erythema nodosum: etiologic and predictive factors in a defined population. Arthritis Rheum 2000; 43:584.
  125. Neville E, Walker AN, James DG. Prognostic factors predicting the outcome of sarcoidosis: an analysis of 818 patients. Q J Med 1983; 52:525.
  126. Milman N, Selroos O. Pulmonary sarcoidosis in the Nordic countries 1950-1982. II. Course and prognosis. Sarcoidosis 1990; 7:113.
  127. Grunewald J, Eklund A. Sex-specific manifestations of Löfgren's syndrome. Am J Respir Crit Care Med 2007; 175:40.
  128. Mañá J, Gómez-Vaquero C, Montero A, et al. Löfgren's syndrome revisited: a study of 186 patients. Am J Med 1999; 107:240.
  129. Grunewald J, Eklund A. Löfgren's syndrome: human leukocyte antigen strongly influences the disease course. Am J Respir Crit Care Med 2009; 179:307.
  130. Okamoto H, Mizuno K, Imamura S, et al. Erythema nodosum-like eruption in sarcoidosis. Clin Exp Dermatol 1994; 19:507.
  131. Löfgren S. Erythema nodosum: study on etiology and pathogenesis in 185 adult cases. Acta Med Scand 1946; suppl 174.
  132. Marie I, Lecomte F, Levesque H, et al. Löfgren's syndrome as the first manifestation of acute infection due to Chlamydia pneumoniae: a prospective study. Clin Infect Dis 1999; 28:691.
  133. Scofield-Kaplan SM, Patel SY, Mueller A, et al. Foreign-Body Granulomata Caused by Injected Permanent Filler Masquerading as Cutaneous Sarcoidosis. Ophthalmic Plast Reconstr Surg 2019; 35:e82.
  134. Cohen Aubart F, Lhote R, Amoura A, et al. Drug-induced sarcoidosis: an overview of the WHO pharmacovigilance database. J Intern Med 2020; 288:356.
  135. Statement on sarcoidosis. Joint Statement of the American Thoracic Society (ATS), the European Respiratory Society (ERS) and the World Association of Sarcoidosis and Other Granulomatous Disorders (WASOG) adopted by the ATS Board of Directors and by the ERS Executive Committee, February 1999. Am J Respir Crit Care Med 1999; 160:736.
  136. Wanat KA, Rosenbach M. A practical approach to cutaneous sarcoidosis. Am J Clin Dermatol 2014; 15:283.
  137. Errichetti E, Stinco G. Dermatoscopy of Granulomatous Disorders. Dermatol Clin 2018; 36:369.
  138. Segurado-Miravalles G, Fernández-Nieto D, Suárez-Valle A, et al. Reflectance confocal microscopy of cutaneous sarcoidosis. Skin Res Technol 2021; 27:980.
  139. Miida H, Ito M. Tuberculoid granulomas in cutaneous sarcoidosis: a study of 49 cases. J Cutan Pathol 2010; 37:504.
  140. Moss J, Zic J, Drake W. Mycobacterial infection masquerading as cutaneous sarcoidosis. Clin Exp Dermatol 2009; 34:e199.
  141. Costabel U, Hunninghake GW. ATS/ERS/WASOG statement on sarcoidosis. Sarcoidosis Statement Committee. American Thoracic Society. European Respiratory Society. World Association for Sarcoidosis and Other Granulomatous Disorders. Eur Respir J 1999; 14:735.
  142. Newman LS, Rose CS, Maier LA. Sarcoidosis. N Engl J Med 1997; 336:1224.
  143. Haimovic A, Sanchez M, Judson MA, Prystowsky S. Sarcoidosis: a comprehensive review and update for the dermatologist: part II. Extracutaneous disease. J Am Acad Dermatol 2012; 66:719.e1.
  144. Müller-Quernheim J. Sarcoidosis: immunopathogenetic concepts and their clinical application. Eur Respir J 1998; 12:716.
  145. Christophi GP, Caza T, Curtiss C, et al. Gene expression profiles in granuloma tissue reveal novel diagnostic markers in sarcoidosis. Exp Mol Pathol 2014; 96:393.
Topic 13762 Version 18.0

References

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