Acquired ichthyosis

Sarcoidosis is an acquired idiopathic, multisystem disorder characterized by noncaseating granulomas in the involved tissue. This condition of unknown

origin is most common in African Americans and northern Europeans. The organs most commonly affected are the lungs, lymph nodes, skin, and eyes. [1-4] Sarcoidosis typically causes no significant derangements, but on occasion the granulomas can become so large or numerous that they impair the function of the affected organ.

Sarcoidosis is the result of an immune dysfunction. The immunological features associated with the condition include impaired delayed-type hypersensitivity reactions to cutaneous antigens (anergy), a shift of helper T lymphocytes from the peripheral blood to sites of disease activity (lymphopenia), and increased production of circulating antibodies. [5] At the site of a non-specific insult, an exaggerated helper T lymphocyte response causes those cells to accumulate, along with macrophages and other elements, until a granuloma forms.

In patients with systemic sarcoidosis, skin lesions occur in 20% to 35% of cases. [6] Cutaneous sarcoidosis without systemic involvement occurs in approximately 25% of patients. [7] Because of its diverse skin manifestations, sarcoidosis is most frequently diagnosed by a dermatologist. Table 1 lists the various clinical manifestations of sarcoidosis of the skin. The skin lesions may be specific or nonspecific. Specific skin lesions are generally associated with chronic disease and demonstrate noncaseating granulomas in the dermis on histological examination. Nonspecific skin lesions are seen primarily with acute disease and noncaseating granulomas are absent.

Specific Skin Lesions

Minus and Grimes reported that flesh-colored waxy papules are the most frequent cutaneous manifestation of sarcoid in African Americans. [8] These skin lesions occur mainly on the face and are frequently symmetrical. Common locations include the periorbital, perinasal, intranasal, perioral, and occipital areas (Figures 1 and 2). Lichenoid papules of sarcoidosis are multiple and violaceous (purplish) skin lesions that are usually found clustered on the trunk. [9]

Hypopigmented macules either alone or in combination with other sarcoid skin lesions occur quite often in African American patients [10,11] (Figure 3). These light areas of skin can resemble other dermatological conditions, such as tinea versicolor, post-in-flammatory hypopigmentation, vitiligo, and T cell lymphoma of the skin (mycosis fungoides). The diagnosis is easily made by performing a skin biopsy, which in sarcoidosis will reveal noncaseating granulomas.

Sarcoidal plaques present as raised erythematous /violaceous, indurated, and shiny skin lesions on the face and extremities (Figure 4). They may become annular in shape and the center of the plaque may become atrophic. If a skin lesion has telangiectatic blood vessels on the surface, it is described as angiolupoid. [12]

The most characteristic of all sarcoid skin lesions is lupus pernio. [13] It presents as chronic sarcoidal plaques with a predilection for the nose, ears, lips, and malar areas of the face. Permanent scarring can occur. Lupus pernio is associated with extensive pulmonary infiltration and scarring, chronic uveitis, and bone cysts. When present on the nose, granulomatous infiltration of the nasal mucosa and the upper respiratory tract can occur. [14] This may progress to destruction of the nasal septum. If a patient presents with lupus pernio, the clinician needs to examine the hands. A bulbous or sausage-shaped appearance of the fingers indicates the presence of an underlying bone lesion. Radiological examination will likely reveal bone cysts.

Subcutaneous nodules of sarcoidosis, also called Darier-Roussy sarcoidosis, [15] appear most often on the arms and legs. These are typically nontender. The overlying skin can be flesh-colored or hypopigmented. These subcutaneous nodules may occur alone [16] or in association with other cutaneous lesions. [17] On biopsy, these show noncaseating granulomas in the dermis and subcutaneous tissue.

Ichthyosiform sarcoidosis is an uncommon skin manifestation of sarcoidosis. [17-20] It presents as hyperpigmented polygonal-shaped scaly areas on the lower extremities (Figure 5). They appear "fish-like" and on histo-logical examination, noncaseating granulomas are found. This type of sarcoidosis can appear either concurrently with or precede the diagnosis of systemic sarcoidosis. The differential diagnosis of a patient who presents with acquired ichthyosis of the skin should also include human immunodeficiency virus disease, lymphoproliferative skin malignancies (such as non-Hodgkin's lymphoma), and cancer of the breast, cervix, or lungs. [21]

Scars from herpes zoster, [22] trauma, surgery, tattoos, [23] or venipuncture also may become swollen and tender and show noncaseating granulomas consistent with sarcoidosis. This can represent either an initial presentation or a reactivation of pre-existing disease.

Other specific reaction patterns of sarcoidosis include ulcerative, psoriasiform (resembling psoriasis), [24] morpheaform (resembling morphea or localized scleroderma), [25] and verruciform (wart-like) [26] skin lesions. Generalized erythroderma, [27] oral lesions, nail dystrophy, scarring alopecia of the scalp (Figure 6), and a pruritic maculopapular eruption also have been reported. Scarring alopecia can be a significant problem for middle-aged African American women who experience hair loss. Alopecia in this population is more often a result of chronic use of hair care products to relax or straighten the hair. These lye and no-lye hair chemicals cause inflammation of the scalp, which result in scarring. A scalp biopsy can help differentiate these 2 distinct entities.

Nonspecific Skin Lesions

Erythema nodosum is the most common nonspecific skin lesion in sarcoid patients. It is a hypersensitivity reaction of the skin to an antigen and is found in association with a number of different infectious and inflammatory diseases (see Table 2). Erythema nodosum presents with painful erythematous subcutaneous nodules on the lower legs. The thighs and arms can occasionally be involved. Systemic systems, such as fever, malaise, and polyarthralgias, can occur in 50% of patients. [28] This acute form of sarcoidosis is called Lofgren's syndrome and is associated with a high rate of spontaneous resolution. Other nonspecific skin manifestations of sarcoidosis include erythema multiforme, calcinosis cutis, nummular eczema, and pruritus.

Diagnosis

Sarcoidosis should be considered as a diagnosis for all chronic skin diseases in African Americans. (The condition is also common among northern Europeans, especially Swedes). The definitive diagnosis of sarcoidosis is the demonstration of noncaseating granulomas in the involved tissue. Special stains for fungi and acid fast bacilli should be done in order to rule out fungal infection, tuberculosis, leprosy, and berylliosis. Laboratory abnormalities include increased serum levels of angiotensin-converting enzyme (ACE), hypercalcemia, anemia, leukopenia, thrombocytopenia and an elevated erythrocyte sedimentation rate. The serum ACE level is elevated in approximately 60% of patients and is a useful test in monitoring the clinical course of the disease. [29]

Treatment

Therapy for sarcoidosis is mostly palliative. The most effective agents used to treat cutaneous sarcoidosis are corticosteroids. Treatment is based upon the location and severity of the skin lesions. High potency topical corticosteroid creams or ointments are used for limited disease while systemic corticosteroids such as prednisone are used for generalized disease. Intralesional injections of triamcinolone acetonide are effective in treating indurated and disfiguring skin lesions.

Chloroquine and hydroxychloroquine (Plaquenil) are antimalarial agents used to treat chronic skin lesions in sarcoid patients. [30] These are very effective as steroid-reducing agents. Side effects include ocular complications and hemolytic anemia.

Other drugs used in the management of sarcoidosis include immunosuppressive agents, such as methotrexate, [31] azathioprine, and chlorambucil. Cosmetic surgery is also used to treat small lesions by excision and extensive sarcoid ulcers by skin grafting. [32,33]

Cutaneous sarcoidosis has many clinical manifestations, which can resemble an array of various skin diseases. Patients with sarcoidosis present not only to dermatologists, but also to clinicians of many different specialties. Factors that determine the clinical manifestations are (1) race, (2) duration of the disease, (3) site and extent of tissue involvement, and (4) activity of the granulomatous process. African American patients with sarcoidosis commonly present with multiple waxy flesh-colored papules on the face as well as hypopigmented skin lesions on the body. These chronic skin lesions that do not resolve on their own must be biopsied. Early diagnosis and treatment of cutaneous sarcoidosis is imperative in order to prevent permanent scarring of the skin and to improve the morbidity and mortality of systemic sarcoidosis.

Valerie D. Callender, MD, FAAD, is a practicing dermatologist in Washington, DC, and Mitchellville, Md. She is a clinical assistant professor of dermatology at the Howard University College of Medicine and the founder and medical director of the Mitchellville Skin and Laser Center.

References

(1.) Zax RH, Callen JP. Sarcoidosis. Dermatol Clin. 1989;7:505-515.

(2.) Kerdel FA, Moschella SL. Sarcoidosis: an updated review. J Am Acad Dermatol. 1984;11:1-19.

(3.) Labow TA, Atwood WG, Nelson CT. Sarcoidosis in the American Negro. Arch Dermatol. 1964;89:682.

(4.) Sharma OP. Cutaneous sarcoidosis: clinical features and management. Chest. 1972;61:320-325.

(5.) James DG, Williams WJ. Immunology of sarcoidosis. Am J Mcd. 1982;72:5-8.

(6.) Samtsov AV. Cutaneous sarcoidosis. Int J Dermatol. 1992;31:385-391.

(7.) Hanno R, Needelman A, Eiferman RA, Callen JP. Cutaneous sarcoidal granulomas and the development of systemic sarcoidosis. Arch Dermatol. 1981;117: 203-207.

(8.) Minus HR, Grimes PE. Cutaneous manifestations of sarcoidosis in blacks. Cutis. 1983;32:361-3, 372.

(9.) Okamoto H, Horio T, Izumi T. Micropapular sarcoidosis simulating lichen nitidus. Dermatologica. 1985;170:253.

(10.) Cornelius CE III, Stein KM, Hanshaw WJ, Spott DA. Hypopigmentation and sarcoidosis. Arch Dermatol. 1973;108:249.

(11.) Thomas RH, McKee PH, Black MM. Hypopigmented sarcoidosis. J R Soc Med. 1981;74:921-923.

(12.) Rongioletti F, Bellisomi A, Rebora A. Disseminated angiolupoid sarcoidosis. Cutis. 1987;40:341-343.

(13.) Spiteri MA, Matthey F, Gordon T, Carstairs LS, James DG. Lupus pernio: A clinico-radiological study of thirty five cases. Br J Dermatol. 1985;112:315- 322.

(14.) Jorizzo JL, Koufman JA, Thompson JN, White WL, Shar GG, Schreiner DJ. Sarcoidosis of the upper respiratory tract in patients with nasal rim lesions: a pilot study. J Am Acad Dermatol. 1990;22:439-443.

(15.) Darier J, Roussy G. Un cas de tumeurs benignes multiples: sarcoides sous-cutanees ou tuberculides nodulaires hypodermiques. Bull Soc Franc Derm Syph. 1904;2:144.

(16.) Vainsencher D, Winkelmann RK. Subcutaneous sarcoidosis. Arch Dermatol. 1984;120:1028-1031.

(17.) Cather JC, Cohen PR. Ichthyosiform Sarcoidosis. J Am Acad Dermatol. 1999;40:862-865.

(18.) Kauh YC, Goody HE, Luscombe HA. Ichthyosiform sarcoidosis. Arch Dermatol. 1978;114:100-101.

(19.) Mountcastle ME, Lupton GP. An ichthyosiform eruption of the legs: sarcoidosis. Arch Dermatol. 1989;125:1415-1419.

(20.) Banse-Kupin L, Pelachyk JM. Ichthyosiform sarcoidosis: report of two cases and a review of the literature. J Am Acad Dermatol. 1987;17:616-20.

(21.) Flint GL, Ham M, Soter NA. Acquired ichthyosis. A sign of nonlymphoproliferative malignant disorders. Arch Dermatol. 1975;111:1446.

(22.) Bisaccia E, Scarborough DA, Carr RD. Cutaneous sarcoid granuloma formation in herpes zoster scars. Arch Dermatol. 1983;119:788-789.

(23.) Dickinson JA. Sarcoidal reactions in tattoos. Arch Dermatol, 1969;100:315-319.

(24.) Schwartz RA, Robertson DB, Tierney LM Jr. McNutt LS. Generalized ulcerative sarcoidosis. Arch Dermatol. 1982; 118:931-933.

(25.) Burov EA, Kantor GR, Isaac M. Morpheaform sarcoidosis: report of three cases. J Am Aced Dermatol. 1998;39:345-348.

(26.) Glass LA, Apisarnthanarax P. Verrucous sarcoidosis simulating hypertrophic lichen planus. Int J Dermatol. 1989;28:539-541.

(27.) Morrison JG. Sarcoidosis in a child, presenting as an erythroderma with keratotic spines and palmar pits. Br J Dermatol. 1976;95:93-97.

(28.) Wood BT, Behlen CH II, Weary PB. The association of sarcoidosis, erythema nodosum, and arthritis. Arch Dermatol. 1966;94:406-408.

(29.) Romer FK. Angiotensin-converting enzyme activity in sarcoidosis and other disorders. Sarcoidosis. 1985;2:25-34.

(30.) Adams J, Diz MM, Sharma OP. Effective reduction in the serum. 1-25-dihydroxy vitamin D and calcium concentration in sarcoidosis-associated hypercalcemia with short-course chloroquine therapy. Ann Intern Med. 1989;111:437-488.

(31.) Veien NK, Brodthagen H, Cutaneous sarcoidosis treated with methotrexate. Br J Dermatol. 1977;97:213-216.

(32.) Shaw M, Black MM, Davis PK. Disfiguring lupus pernio successfully treated with plastic surgery. Clin Exp Dermatol. 1984;9:614.

(33.) Collison DW, Novice F, Banse L, Rodman OG, Kelly AP. Split-thickness skin grafting in extensive ulcerative sarcoidosis. J Dermatol Surg Oncol. 1989;15: 679-683.

Cutaneous Manifestations of Sarcoidosis.

Specific Skin Lesilons

(Associated With Chronic Disease)

* Flesh colored "waxy" papules

* Lichenaid papules

* Hypopigmented macules

* Annular plaques

* Lupus pernia

* Subcutaneous nodules (Darier-Roussy Sarcoidosis)

* Nodules

* Ichthyosiform

* Psoriasiform

* Ulcerative

* Within scars

* Generalized erythroderma

* Oral lesions

* Scarring alopecia of the scalp

* Morpheaform

* Verruciform

* Pruritic maculopapular eruption

* Nail dystrophy

Nonspecific Skin Lesions

(Associated With Acute Disease)

* Erythema nodosum

* Erythema multiforme

* Calcinosis cutis

* Nummular eczema

* Pruritus

Causes of Erythema Nodosum [1]

Infections

Streptococci

Tuberculosis

Psittacosis

Yersiniosis

Lympho granuloma venereum

Cat-Scratch disease

Coccidia idomycosis

Upper respiratory infection

* Drugs

Sulfonamides

Bromides

Oral contraceptives

* Systemic Illnesses

Sarcoidosis (Lofgren's Syndrome)

Inflammatory Bowel Disease

Hodgkin's Lymphoma

Pregnancy

(1.) Taken from Habif TP, Clinical Dermatology

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