CLINICAL HISTORY:

Signs and symptoms:  A 79 year old female presented with a 2 weeks history of a progressively worsening pruritic rash that began on her right upper arm then the left arm and upper back. She is not sure if light makes the rash worse. She denies any changes in her medications with the exception of the addition of lisinopril three months ago.

Previous Treatment:  None

Other information:  Medications: Lisinopril, Lipitor, Pacerone, Timolol, Aspirin, Xalantin, Timoptic

PHYSICAL EXAM:

An elderly appearing female with multiple annular and arciform nonindurated plaques with trailing scale and lacking follicular plugging affecting the lateral aspects of the arms bilaterally and the upper back. She is afebrile and without lymphadenopathy.

LABORATORY TESTS:

ANA + (1:320, Nucleolar pattern), SS-A antibody > 8.0 positive, SS-B antibody 1.0 positive, ds-DNA antibody negative, SCL-70 negative, Anti-Histone negative. CBC, Liver and Renal functions all within normal limits.

DERMATOHISTOPATHOLOGY:

Two 5 mm punch biopsies were performed. The first punch biopsy was on the outer border of an annular plaque of the right arm for H&E. The second was a perilesional biopsy of normal appearing skin from the left arm for Direct Immunofluorescence (DIF).

A DIF image was not available, but it demonstrated linear and granular deposits of IgG, IgA, and IgM, along with C3, at the dermal-epidermal junction and extending into the superficial dermis.

The H&E reveals slight hyperkeratosis overlying a focally acanthotic but focally flattened epidermis. A superficial perivascular and somewhat lichenoid lymphocytic inflammatory infiltrate with exocytosis of lymphocytes into the epidermis. Scattered necrotic keratinocytes are seen. A PAS stain does not reveal significant thickening of the dermal-epidermal junction basement membrane, and fungal organisms are absent. A colloidal iron stain demonstrates mildly increased reticular dermal mucin.

H & E 4X

H & E Interface

H & E 40X Necrotic Keratinocytes

DIFFERENTIAL DIAGNOSIS:

1.   Erythema Annulare Centrifugum
2.   Tinea Corporis
3.   Psoriasis
4.   Subacute Cutaneous Lupus Erythematosus
5.   Granuloma Annulare

SCROLL DOWN FOR ANSWER AND DISCUSSION.

CORRECT DIAGNOSIS:

Subacute Cutaneous Lupus Erythematosus

DISCUSSION:

Subacute Cutaneous Lupus Erythematosus (SCLE) is a recurring, photosensitive, nonscarring, nonindurated and superficial lesion with two primary forms, annular and/or papulosquamous. It may be seen in patients ranging from 1 � years of age to the elderly, but it primarily affects Caucasian females in the 4th decade. It is uncommonly seen in African-American, Chinese and Korean populations. SCLE affects the extensor arms & shoulders, upper trunk and �V� of neck as well as forearms and dorsal hands usually sparing the knuckles and rarely involving the face. On photochallenge testing, 100% of SCLE patients had abnormal reactions to ultraviolet light. SCLE is associated with HLA-A1, B8 and DR3 as well as deficiency or lack of C2 or C4. Also, a new genetic association exists in a single nucleotide polymorphism in a gene promoter region for TNF-α.
The proposed pathogenesis progresses through four sequential stages. A genetically susceptible individual experiences a loss of self tolerance/autoimmunity induction. The autoimmune process expands, culminating in tissue injury and manifestation of disease. Histologically, it is common to see epidermal atrophy. The basal layer keratinocytes appear hydropic or have eosinophilic degeneration. The upper dermis demonstrates a sparse interface and perivascular lymphohistiocytic infiltrate. On direct immunofluorescence of 60% of SCLE cases a granular band of immunoglobulin and complement is seen at the dermo-epidermal junction (DEJ). Alternatively, a dust-like deposition of IgG can be seen over epidermal basal cells and below the DEJ.
Drug induced autoantibody production was appreciated in 1985, and these autoantibodies were of the Ro/SS-A type. Seventy percent of patients with SCLE have antinuclear antibody and Ro/SS-A positivity. Autoantibodies to La/SS-B are also common. Less commonly seen are autoantibodies to double-stranded DNA and Smith. Today, many common medications have been associated with development of SCLE lesions, including calcium channel blockers, diuretics, angiotensin converting enzyme inhibitors, antihistamines, seizure medications, antimalarials, sulfonylureas, chemotherapeutics, and others to include etanercept and infliximab.
Of the patients with SCLE lesions, 20% will develop either discoid or acute cutaneous LE lesions. Leukocytoclastic vasculitis, Raynaud�s phenomenon and Livedo reticularis are also seen. Almost half will have 4 or more criteria for systemic lupus erythematosus (SLE), but they usually lack renal and CNS disease. Ten to fifteen percent will develop SLE. Forty-three percent of patients develop Sj�gren�s syndrome, which also has Ro/SS-A autoantibodies. Other disease associations with SCLE include autoimmune thyroiditis, hereditary angioedema, and autoimmune polyglandular syndrome type II.

TREATMENT:

Treatment of SCLE emphasizes photoprotection by way of avoidance and broad spectrum sunscreens. Topical corticosteroids, tacrolimus and pimecrolimus are also effective for improving the SCLE lesions. Systemic therapy with hydroxychloroquine, chloroquine, or quinacrine is effective in 75% of patients. Interestingly, these medications are ineffective in cigarette smoking patients. Thalidomide is also effective, but its use is limited due to toxicity. Dapsone, clofazamine and gold formulations have been used also. Methotrexate, Azathioprine, and mycophenolate mofetil can be considered in recalcitrant cases.

REFERENCES:

1. Sontheimer RD. Subacute cutaneous lupus erythematosus: 25-year evolution of a prototypic subset (subphenotype) of lupus erythematosus defined by characteristic cutaneous, pathological, immunological, and genetic findings. Autoimmunity Reviews 2005; 4: 253-263.
2. Werth VP. Clinical Manifestations of Cutaneous Lupus. Autoimmunity Reviews 2005; 4: 296-302.
3. Franceschini F, Cavazzana I. Anti-Ro/SSA and La/SSB antibodies. Autoimmunity 2005; 38(1): 55-63.
4. Tebbe B. Clinical Course and Prognosis of Cutaneous Lupus Erythematosus. Clinics in Dermatology 2004; 22:121-124.
5. Albrecht J, Berlin JA, Braverman IM et al. Dermatology position paper on the revision of the 1982 ACR criteria for systemic lupus erythematosus. Lupus 2004; 13: 839-849.
6. Chlebus E, Wolska H, Blaszczyk M, Jablonska S. Subacute cutaneous lupus erythematosus versus systemic lupus erythematosus: Diagnostic criteria and therapeutic implications. Journal of the American Academy of Dermatology 1998; 38: 405-412.
7. Sontheimer RD, Thomas JR, Gilliam JN. Subacute cutaneous lupus erythematosus: a cutaneous marker for a distinct lupus erythematosus subset. Archives of Dermatology 1979; 115: 1409�15.

Additional Comment:

The author would like to thank Steven Ruhoy, MD for providing the histology images.

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