Skip to main content
eScholarship
Open Access Publications from the University of California

Dermatology Online Journal

Dermatology Online Journal bannerUC Davis

Chronic cutaneous lupus erythematosus in vitiligo

Main Content

Chronic cutaneous lupus erythematosus in vitiligo
Hillary Johnson MD PhD, Nicole Bossenbroek MD, Karla Rosenman MD, Shane A Meehan MD, Mirin Robles MD, Miriam K Pomeranz MD
Dermatology Online Journal 14 (10): 10

Department of Dermatology, New York University

Abstract

A 49-year-old woman presented with a seven-year history of pruritic, erythematous, scaling plaques on sun-exposed skin that localized only to pre-existing depigmented patches. Histopathologic examination showed changes consistent with cutaneous lupus erythematosus with lichenoid features and confirmed contiguous vitiligo. Diagnosis of chronic cutaneous lupus erythematosus localized to areas of vitiligo was determined by clinicopathologic correlation and may reflect an autoimmune diathesis. Consequently, hydroxychloroquine and topical glucocorticoids therapy were initiated with reported improvement in pruritus, erythema, and scale. Clinical monitoring for development of squamous-cell carcinoma in areas of chronic inflammation and sun-exposure is imperative.



Figure 1Figure 2

History

A 49-year-old Bangladeshi woman, who recently relocated to the United States, presented to the Dermatology Clinic at Bellevue Hospital Center in September, 2007, with a seven-year history of a pruritic, erythematous, scaling eruption localized to areas of pre-existing vitiligo of 15-year duration. The patient lacked systemic complaints. Family history of vitiligo and other cutaneous disorders was denied. The patient had a medical history of diabetes mellitus since 1999 that was treated with glicazide and pioglitazone. In 2002, the patient underwent electron-beam radiation therapy to the right extensor forearm for invasive squamous-cell carcinoma in the setting of a non-specific dermatitis according to a 2006 histopathology report. Additional surgical history included appendectomy and hysterectomy. She denied a history of tobacco use or chemical exposure. Review of medical records from India showed past treatment of unknown duration with hydroxychloroquine 200 mg twice daily, acitretin 10 mg once daily, tazarotene cream, topical glucocorticoids (clobetasol ointment, clobetasone butyrate ointment, or betamethasone cream), vitamin E cream, or collagen elastin cream for prior diagnoses of psoriasis and cutaneous lupus erythematosus. Fexofenadine and hydroxyzine had been provided for pruritus. The patient did not recall if the prior therapies resulted in clinical improvement.

After review of laboratory and histopathologic data obtained at the Bellevue Hospital Center, hydroxychloroquine 200 mg twice daily was initiated. In conjunction, affected areas were treated with clobetasol propionate 0.05 percent ointment twice daily on the trunk and extremities or fluocinolone acetonide 0.025 percent ointment twice daily on the face. In the subsequent two weeks, she reported reduction in pruritus, erythema, and scale.


Physical Examination

Generalized, well-demarcated, depigmented patches with enhancement under Wood's lamp examination were present on the face, postauricular neck, abdomen, back, buttocks, extensor apects of the arms and legs, and dorsal aspects of the hands. Many of the depigmented patches contained focal, round, normally-pigmented, brown macules within them. Within some of the depigmented patches on the face, forearms, and back were focal, brightly erythematous scaling plaques. Notably, the back was a sun-exposed area in this patient due to daily attire in Indian clothing (sari or saree). Similar erythematous, scaling plaques were observed in the conchal bowls and the mucosal lips. On the right extensor aspect of the forearm, one of the erythematous, scaling plaques was depressed at the site of past electron beam radiation for squamous-cell carcinoma. The patient exhibited frontal alopecia without evidence of scars. Examination of the nails was limited by the prior application of henna dye, but they did not appear abnormal.


Lab

A complete blood count, fasting lipid profile, and thyroid function panel were normal. Comprehensive metabolic panel showed an elevated serum glucose of 162 mg/dL, and hepatic function panel showed an elevated alkaline phosphatase of 113 IU/L. Erythrocyte sedimentation count and c-reactive protein were elevated at 55 mm/hr and 15.95 mg/L respectively. Anti-nuclear antibody, double-stranded DNA antibody, Smith antibody, ribonucleoprotein antibody, and rheumatoid factor were not detected. The Sjogren's single-stranded A index was elevated at 1.65 units (normal index ≤1.00) while Sjogren's single-stranded B antibody index was normal. Urinalysis and glucose-6-phosphate dehydrogenase level were normal.


Histopathology

There is a band-like lymphocytic infiltrate, with a vacuolar change and necrotic keratinocyte at the dermoepidermal junction. There is epidermal acanthosis, hypergranulosis, and hyperkeratosis. Thickening of the basement membrane and hyalinization of dilated superficial blood vessels are present. A S100 stain shows a loss of epidermal melanocytes. Acid-fast bacillus and Steiner stains for mycobacteria and spirochetes are negative.


Comment

Chronic cutaneous lupus erythematosus (CCLE) is an inflammatory and photosensitive dermatosis that likely stems from a poorly understood immune dysregulation with an autoimmune reaction in genetically predisposed individuals. While patients with systemic lupus erythematosus (SLE) may have cutaneous involvement, studies estimate CCLE progression to SLE in less than 5 percent to 10 percent. CCLE occurs more frequently in women and is often characterized by erythematous, scaling plaques but may exhibit clinical variability, such as hypertophic or lichenoid features. Serologic abnormalities are not common; however, some patients with CCLE exhibit positive antinuclear antibody, double-stranded DNA antibody, or Smith antibody. Sjogren's single-stranded A (SS-A or Ro) autoantibody may be found in a small percentage of patients with CCLE. Typical treatment includes photoprotection, topical or intralesional glucocorticoids, or antimalarial medication. Alternative therapies include retinoids or immunosuppressive agents, such as thalidomide, methotrexate, mycophenolate mofetil, or azathioprine [1-9].

Coexistence of cutaneous lupus erythematosus (CLE) and vitiligo has been infrequently reported [10-18]. Vitiligo is a part of systemic autoimmune dysregulatory process with underlying genetic susceptibility since approximately 30 percent with generalized vitiligo have associated autoimmune disorders, such as thyroid disease, diabetes mellitus, and alopecia areata. Unlike CLE, there is no sex-related predilection [19, 20, 21]. Autoimmune endocrinopathy and cutaneous disease have been linked to syndromes of systemic immune disorder. Diabetes mellitus has been associated with vitiligo, and a number of connective-tissue disorders that include SLE [22, 23]. In murine models, antibodies obtained from the sera of non-obese diabetic mice exhibit nuclear and cytoplasmic staining similar to the pattern observed in autoimmune connective-tissue diseases [24].

In the case presented, an autoimmune diathesis with sequential development of generalized vitiligo in 1992, diabetes mellitus in 1999, and CLE in 2002 was notable. In published literature, the majority of patients with concurrent CLE and vitiligo resided in regions with potential chronic sun exposure, such as India and southern Europe [10-18]. Thus, photosensitivity and chronic sun exposure may serve as a triggering factor although it is unclear if formation of CLE in vitiligo represents a transformation or collision of two cutaneous disorders. In lupus erythematosus, ultraviolet B-induced apoptotic and necrotic keratinocytes are putative targets for autoantibodies and mediators of inflammatory cascades. A reported association between autoantibody specificities for Sjogren's single-stranded antibodies (SS-A/Ro and SS-B/La) and CLE is controversial due to poor reproducibility [25].

Ultravioletlight exposure and chronic inflammation play roles in development of squamous-cell carcinoma (SCC), a known complication of CCLE. While SCC formation in long-standing vitiligo is rare, it has been associated with PUVA photochemotherapy and with intense sun exposure [26, 27, 28, 29, 30]. Squamous-cell carcinomas, sometimes multiple, have been described as arising in lesions of CCLE [15, 31]. In addition, KA and SCC may be difficult to distinguish from hypertrophic LE [32].The appearance of keratoacanthoma has been reported in a 65-year-old Indian woman with generalized vitiligo, in whom the depigmented patches on sun-exposed areas contained erythematous, scaling, sclerotic plaques considered to be secondary actinic change or chronic discoid lupus erythematosus. The keratoacanthoma erupted rapidly in an existing depigmented and sclerotic plaque that had been noted for several years [17]. Our patient presented with a history of invasive squamous cell carcinoma arising from a similar appearing depigmented and inflammatory lesion on the forearm. Thus, exposure to ultraviolet light may potentiate the appearance of CCLE and complication of SCC in patients with vitiligo.

References

1. Werth VP. Clinical manifestations of cutaneous lupus erythematosus. Autoimmunity Reviews 2005; 4: 296 PubMed

2. Prystowsky SD, Gilliam JN. Discoid lupus erythematosus as part of a larger spectrum. Arch Dermatol 1975; 111: 1448 PubMed

3. Attili SK, Attili VR. Keratoacanthoma centrifugum marginatum arising in vitiligo: a case report. Dermatol Online J 2006; 12: 18 PubMed

4. Saihan EM, Peachy DG. Vitiligo and morphoea. Clin Exp Dermatol 1979; 4: 103 PubMed

5. Choudhry DS. Development of discoid lupus erythematosus in vitiligo. Bull Calcutta Sch Trop Med 1968; 16: 111

6. Uitto J, et al. Verrucous lesions in patients with discoid lupus erythematosus. Br J Dermatol 1978; 98: 507 PubMed

7. De Barker D, et al. The sequelae of chronic cutaneous lupus erythematosus. Lupus 1992; 1:181

8. Gul U, et al. Vitiligo associated with malignant melanoma and lupus erythematosus. J Dermatol 2007; 34: 142 PubMed

9. Ingber A, et al. Squamous cell carcinoma in discoid lupus erythematosus foci. Z Hautkr 1983; 58: 1289 PubMed

10. Khare AK, et al. Vitiligo and disseminated discoid lupus erythematosus. Indian J Dermatol 198; 33: 37 PubMed

11. Passarinin B, et al. Appearance of vitiligo in patients with chronic discoid erythematosus. G Ital Dermatol Venereol 1985; 120: 425 PubMed

12. Callen JP. Discoid lupus erythematosus in a patient with vitiligo and autoimmune thyroiditis. Int J Dermatol 1984; 23: 203 PubMed

13. Forrestier JY, et al. Association of lupus erythematosus and vitiligo. Ann Dermatol Venereol 1981; 108: 33 PubMed

14. Khosravi AR, et al. Case report: chronic dermatophyte infection in a patient with vitiligo and discoid lupus erythematosus. Mycoses 2000; 43:317 PubMed

15. Kar BR, et al. Squamous cell carcinoma of the scalp arising from chronic cutaneous lupus erythematosus: report of two Indian patients. Indian J Dermatol Venereol Leprol 2004; 70: 236 PubMed

16. Sulica VI, et al. Squamous-cell carcinoma of the scalp arising in lesions of discoid lupus erythematosus. Am J Dermatopathol 1988; 10: 137 PubMed

17. Park HS, et al. Squamous cell carcinoma in vitiligo lesion after long-term PUVA therapy. J Eur Acad Dermatol Venereol 2003; 17: 578 PubMed

18. Callen JP, Klein J. Subacute cutaneous lupus erythematosus: clinical, serologic, immunogenetic, and therapeutic considerations in seventy-two patients. Arthritis Rheum 1988; 31: 1007 PubMed

19. Spritz RA. The genetics of generalized vitiligo and associated autoimmune diseases. J Dermatol Sci 2006; 41: 3 PubMed

20. Gopal KV, et al. Vitiligo: a part of a systemic autoimmune process. Indian J Dermatol Venereol Leprol 2007; 73: 162 PubMed

21. Alkhateeb A, et al. Epidemiology of vitiligo and associated autoimmune diseases in Caucasian probands and their families. Pigment Cell Res 2003; 16: 208 PubMed

22. Birlea SA, Fain PR, Spritz RA. A Romanian population isolate with high frequency of vitiligo and associated autoimmune diseases. Arch Dermatol. 2008 Mar;144(3):310-6. PubMed

23. Gopal KV, Rama Rao GR, Kumar YH, Appa Rao MV, Vasudev P; Srikant. Vitiligo: a part of a systemic autoimmune process. Indian J Dermatol Venereol Leprol. 2007 May-Jun;73(3):162-5. Department of Dermatology, Andhra Medical College, Visakhapatnam, India. kvtgopal@yahoo.co.in. PubMed

24. Silveira PA, Baxter AG. The NOD mouse as a model of SLE. Autoimmunity. 2001;34(1):53-64. PubMed

25. Bijl M, Kallenberg CG. Ultraviolet light and cutaneous lupus. Lupus. 2006;15(11):724-7. Review. PubMed

26. Akimoto S, et al. Multiple actinic keratoses and squamous cell carcinomas on the sun-exposed areas of widespread vitiligo. Br J Dermatol 2000; 142: 824 PubMed

27. Saarinen KA, et al. Actinic damage and squamous cell carcinoma in sun-exposed skin affected by vitiligo. Br J Dermatol 2000; 143: 219 PubMed

28. Seo SL, Kim IH. Squamous cell carcinoma in a patient with generalized vitiligo. J Am Acad Dermatol 2001; 45: 227 PubMed

29. Akimoto S, et al. Multiple actinic keratoses and squamous cell carcinomas on the sun-exposed areas of widespread vitiligo. Br J Dermatol 2000; 142: 824 PubMed

30. Saarinen KA, et al. Actinic damage and squamous cell carcinoma in sun-exposed skin affected by vitiligo. Br J Dermatol 2000; 143: 219 PubMed

31. Garrett AB. Multiple squamous cell carcinomas in lesions of discoid lupus erythematosus. Cutis. 1985 Oct;36(4):313-4, 316. PubMed

32. Daldon PE, Macedo de Souza E, Cintra ML. Hypertrophic lupus erythematosus: a clinicopathological study of 14 cases. J Cutan Pathol. 2003 Aug;30(7):443-8. PubMed

© 2008 Dermatology Online Journal