Lupus profundus_0413 Derm Clinic 1a
Lupus profundus_0413 Derm Clinic 1b
A black woman, aged 37 years and previously diagnosed with systemic lupus erythematosus (SLE), presented with painful lesions on her right arm of four months’ duration. Review of symptoms was remarkable for photosensitivity and joint pain.
Physical exam showed an atrophic tender plaque with overlying depigmentation on her right arm with similar lesions on her forearm and chest. An antinuclear antibody (ANA) test was positive, but anti-double-stranded DNA (dsDNA), anti-Sjögren’s syndrome A (SS-A), and anti-SS-B tests were negative.
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Histopathologic examination of an incisional biopsy from the woman’s arm lesion revealed an inflammatory infiltrate of the subcutis in a lobular pattern with moderate hyalinization and calcification. The diagnosis of lupus erythematosus profudus (LEP), also known as lupus panniculitis, was made based on the clinical and histologic findings.
LEP, a rare variant in the clinical spectrum of lupus erythematosus (LE), accounts for 1% to 3% of all LE cases, and involves inflammation of subcutaneous fat.1,2 Kaposi first described the condition in 1883 as subcutaneous nodules in patients with SLE.3 Irgang coined the term LEP in 1940 and suggested that LEP was a unique skin finding in LE.4 LEP is now believed to represent a distinct variant of LE, as it may occur in the setting of SLE, in association with such other cutaneous forms of LE as discoid LE (DLE); in conjunction with other autoimmune processes; or, rarely, as an isolated skin finding without an underlying condition.5
According to Wu et al., the incidence of LEP is 2% to 10% in SLE patients and 33% to 70% in DLE patients. Women aged 30 to 60 years are most commonly affected, although LEP has been described in children.2 Recent data suggest that the presence of LEP in a patient with SLE may be predictive of a less severe course.3,6
Lesions of LEP commonly present as indurated and firm, tender, or asymptomatic nodules. At times, the lesions develop as sharply defined plaques that arise in crops or appear singly.5 The overlying epidermis is frequently normal in appearance; however, findings of DLE with erythema, atrophy, scaling, ulcerations, follicular plugging, or telangiectasias may be present.5,7 In adults, lesions have a predilection for the proximal upper extremities; the face is more commonly affected in children.7,8 Other frequently affected sites in all patients include the buttocks, chest, breasts, and scalp.5,8 Lesions on the legs are unusual and a useful clinical clue that helps distinguish LEP from other forms of panniculitis.5 Healing of lesions can occur spontaneously or after treatment and often results in atrophic, depressed, and disfiguring scars.5
The pathophysiology of LEP is poorly understood; however, immune complex deposition, as well as T-cell mediated inflammation, have been implicated.6 Some studies suggest that LEP is associated with previous trauma and/or injections.9
The differential diagnosis of LEP includes a variety of panniculitides and conditions that affect the deep dermis, such as erythema nodosum, erythema induratum, lupus tumidus, thrombophlebitis, cold panniculitis, deep morphea, and pancreatic fat necrosis.5 In addition, DLE, Weber-Christian disease, Jessner’s lymphocytic infiltrate, sarcoidosis, dermatomyositis, and subcutaneous panniculitis-like T-cell lymphoma (SPTL) can each be clinically confused with LEP. The diagnosis of LEP is made based on clinical-pathologic correlation because there is no pathognomonic clinical, pathologic, or laboratory finding diagnostic for LEP. SPTL is the most significant of the diagnoses to correctly identify. Although SPTL usually has more systemic symptoms, the pathologic findings may be identical to those of LEP.7 Immunohistochemistry and molecular studies may be necessary to distinguish the two conditions.9
For diagnosis, adequate subcutaneous tissue must be obtained and submitted for histologic evaluation.10 A punch biopsy is readily obtainable in most office settings and may provide an appropriate specimen. However, the size of the specimen obtained is limited with a punch biopsy, and the amount of fat removed for analysis may not be sufficient. An incisional biopsy allows more subcutaneous tissue to be removed for study and thus may be preferable.10
Serologic studies have little role in the diagnosis of LEP because such studies are frequently normal and, even when abnormal, offer too little consistency to be of diagnostic value.7 Elevated ANA, anti-dsDNA, and rheumatoid factor titers have been described; other reported abnormalities include lymphopenia, anemia, transaminitis, and low complement levels, as well as elevated C-reactive protein and sedimentation.5-7 A deficiency in complement C4 has been repeatedly reported and may be of some significance.7
LEP exhibits a chronic and relapsing course and is often difficult to treat.1 The morbidity of the condition is attributable to lesional pain and disfigurement, both of which can be significant.6 Treatment is effective only if implemented during the active, inflammatory phase of the disease; it is ineffective after scarring and atrophy have occurred.1 While there are currently no FDA-approved medications to treat LEP, there are treatment regimens supported by evidence-based medicine.1
Although the role of UV light in exacerbating the disease is controversial, patients should be advised to routinely use a broad-spectrum sunscreen.8 Topical steroids can be tried alone or in combination with other modalities, but the depth of the inflammation may render topical therapy ineffective.11 Intralesional corticosteroids may provide some benefit in limited disease but may result in worsening of cutaneous atrophy or lesional ulceration.1,5-7 Systemic corticosteroids may be highly effective for some patients, but adverse effects limit long term use;5,6 these medications should be reserved for either widespread or resistant disease.12
Such antimalarial medications as hydroxychloroquine 200-400 mg/day and chloroquine 250-500 mg/day, used either alone or in combination with quinacrine 100 mg/day, may be considered first-line systemic therapy for the treatment of LEP.1 The initial course should be between six and 12 weeks; if a response is seen, chronic therapy could be considered.1 Individuals who smoke will not experience the same positive response as that seen in nonsmokers.5,8,12 Although the risk of retinal toxicity is low, all patients receiving an antimalarial medication should be followed by an ophthalmologist.
While potentially more effective than antimalarial therapy, thalidomide 50-300 mg/day is considered a second-tier option because of such potential side effects as teratogenicity and neuropathy.1,5 This medication should be reserved for recalcitrant cases and never used in a patient who could become pregnant.
A variety of immunosuppressive medications have been used in severe and recalcitrant cases, but results are inconsistent.5,6 Medications with variably reported success include azathioprine, mycophenolate mofetil, methotrexate, cyclophosphamide, cyclosporine, and rituximab.1,5,8 Espírito et al. described two cases of recalcitrant LEP that responded to IV immunoglobulin.6 Cosmetic and reconstructive options available to patients severely affected by disfigurement include various lasers, fillers, and autologous fat transfer;1 however, these treatments may exacerbate the disease process and should be used cautiously.5
The woman described in this case was treated with hydroxychloroquine 200 mg b.i.d. for three months. The induration and tenderness of the arm lesion resolved during this time. Unfortunately, the atrophy and color loss did not improve.
Rachel E. Chikowski is a third-year medical student at Medical College of Virginia Hospitals, Virginia Commonwealth University, in Richmond, where Julia R. Nunley, MD, is professor of dermatology.
- Hansen CB, Callen JP. Connective tissue panniculitis: lupus panniculitis, dermatomyositis, morphea/scleroderma. Dermatol Ther. 2010;23:341-349.
- Khoury T, Arayssi T, Kibbi AG, Ghosn S. Extensive fat necrosis with lipomembranous changes and calcification in lupus erythematosus panniculitis is not necessarily associated with systemic lupus erythematosus. Am J Dermatopathol. 2010;32:742-743.
- Wu CY, Chiang CP. Clinicopathologic challenge: multiple tender lesions on both upper extremities and the back. Int J Dermatol. 2010;49:380-381.
- Irgang S. Lupus erythematosus profundus. Arch Dermatol Syphilol. 1940;42:97-102.
- Fraga J, García-Díez A. Lupus erythematosus panniculitis. Dermatol Clin. 2008;26:453-463.
- Espírito Santo J, Gomes MF, Gomes MJ, et al. Intravenous immunoglobulin in lupus panniculitis. Clin Rev Allergy Immunol. 2010;38:307-318.
- Weingartner JS, Zedek DC, Burkhart CN, Morrell DS. Lupus erythematosus panniculitis in children: report of three cases and review of previously reported cases. Pediatr Dermatol. 2012;29:169-176.
- Guissa VR, Trudes G, Jesus AA, et al. Lupus erythematosus panniculitis in children and adolescents. Acta Reumatol Port. 2012;37:82-85.
- Park HS, Choi JW, Kim BK, Cho KH. Lupus erythematosus panniculitis: clinicopathological, immunophenotypic, and molecular studies. Am J Dermatopathol. 2010;32:24-30.
- Rose C, Leverkus M, Fleischer M, Shimanovich I. Histopathology of panniculitis—aspects of biopsy techniques and difficulties in diagnosis. J Dtsch Dermatol Ges. 2012;106:421-425.
- Tsuzaka S, Ishiguro N, Akashi R, Kawashima M. A case of lupus erythematosus profundus with multiple arc-shaped erythematous plaques on the scalp and a review of the literature. Lupus. 2012;21:662-665.
- Koley S, Sarkar J, Choudhary SV, et al. Lupus erythematosus panniculitis: a case report. J Pakistan Assoc Dermatologists. 2011;21:118-121.