Lupus Erythematosus and Localized Scleroderma Coexistent at the Same Sites: a Rare Presentation of Overlap Syndrome of Connective-Tissue Diseases

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Lupus Erythematosus and Localized Scleroderma Coexistent at the Same Sites: A Rare Presentation of Overlap Syndrome of Connective-Tissue Diseases

Anabella Pascucci, MD; Peter J. Lynch, MD; Nasim Fazel, MD, DDS

PRACTICE POINTS • Discoid lupus erythematosus and localized scleroderma may rarely overlap within the same lesions. • Cutaneous overlap syndromes tend to respond well to antimalarials, topicalcopy steroids, and systemic steroids.

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Overlap syndromes are known to occur with lthough lupus erythematosus (LE) and sclero- connective-tissue diseases (CTDs). Rarely, Dothe derma are regarded as 2 distinct entities, overlap occurs at the same tissue site. We report Athere have been multiple cases described the case of a patient with clinical and histopatho- in the literature showing an overlap between these logic findings consistent with the presence of 2 disease processes. We report the case of a discoid lupus erythematosus (DLE) and localized 60-year-old man with clinical and histopathologic scleroderma within the same lesions. Based on findings consistent with the presence of localized our case and other reported cases in the literature, scleroderma and discoid LE (DLE) within the same the following features are common in patients with lesions. We also present a review of the literature and an overlap of lupus erythematosusCUTIS (LE) and local- delineate the general patterns of coexistence of these ized scleroderma: predilection for young women, 2 diseases based on our case and other reported cases. photodistributed lesions, DLE, linear morphology clinically, and positivity along the dermoepider- Case Report mal junction on direct immunofluorescence. Most A 60-year-old man presented with a progressive patients showed good response to antimalarials, pruritic rash on the face, neck, and upper back of topical steroids, or systemic steroids. approximately 20 to 30 years’ duration. On initial Cutis. 2016;97:359-363. evaluation, the patient was found to have indurated hypopigmented plaques with follicular plugging bilaterally on the cheeks, temples, ears, and upper back (Figure 1). Punch biopsies were performed Dr. Pascucci was from and Drs. Lynch and Fazel are from the on the left cheek and upper back. Histopathology Department of Dermatology, University of California Davis School of was notable for vacuolar interface dermatitis with Medicine, Sacramento. Dr. Pascucci currently is from the Division of dermal sclerosis at both sites. Specifically, inter- Dermatology, University of California Los Angeles. face changes, basement membrane thickening, and The authors report no conflict of interest. Correspondence: Anabella Pascucci, MD, UCLA Dermatology, periadnexal inflammation were present on histo- 514 N Prospect Ave, Redondo Beach, CA 90277 pathologic examination from both biopsies sup- ([email protected]). porting a diagnosis of DLE (Figure 2A). However,

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A B C

Figure 1. Indurated hypopigmented plaques with follicular plugging on the left cheek (A), lateral aspect of the neck (B), and upper back (C).

there also was sclerosis present in the reticular der- dermatomyositis,copy and Sjögren syndrome. On the mis, suggesting a diagnosis of localized scleroderma other hand, it is widely recognized that patients (Figure 2B). Direct immunofluorescence was nega- with one classic autoimmune CTD are likely to pos- tive for a lupus band. Laboratory workup was posi- sess multiple autoantibodies, and a small number of tive for antinuclear antibody (titer, 1:40; speckled thesenot patients develop symptoms and/or signs that pattern) and anti–Sjögren syndrome antigen A satisfy the diagnostic criteria of a second autoim- but negative for double-stranded DNA antibody, mune CTD; these latter patients are said to have an anti-Smith antibody, anti–Sjögren syndrome anti- overlap syndrome.1 The development of a second gen B, and Scl-70. Doidentifiable CTD, hence indicating an overlap syn- The patient was started on oral hydroxychlo- drome, may occur coincident to the initial CTD or roquine 200 mg twice daily and clobetasol oint- may occur at a different time.1 ment 0.05% twice daily to affected areas. After Essentially all 5 of the CTDs mentioned above 2 weeks of treatment, he developed urticaria on the have been reported to occur in combination with trunk and the hydroxychloroquine was discontinued. one another. Most of the reports involving overlap He continued using only topical steroids following among these 5 CTDs include patients with mul- a regimen of applying clobetasol ointment 0.05% tiorgan systemic involvement without cutaneous twice daily for 2 weeks, alternatingCUTIS with the use of involvement, leading to a fairly simple straightfor- triamcinolone ointment 0.1% twice daily for 2 weeks ward classification of overlap syndromes as viewed by with improvement of the pruritus, but the indura- rheumatologists.1 However, the situation is not that tion and hypopigmentation remained unchanged. simple for dermatologists based on the fact that skin Alternative systemic medication was started with involvement for 2 of these diseases—scleroderma mycophenolate mofetil 1 g twice daily. The patient and LE—can occur either in a setting of systemic showed remarkable clinical improvement with a disease or in situations where the cutaneous involve- decrease in induration and partial resolution of fol- ment occurs as a stand-alone process. This overlap licular plugging after 4 months of treatment with often occurs with the localized forms of scleroderma mycophenolate mofetil in combination with the (ie, morphea, morphea profunda, linear morphea) topical steroid regimen. and those instances of LE that are primarily limited to the skin (ie, DLE, subacute cutaneous LE, lupus Comment panniculitis). When the overlap occurs between the Autoimmune connective-tissue diseases (CTDs) localized forms of scleroderma and purely cutaneous often occur with a wide range of symptoms and LE, the situation becomes even more complicated, signs. Most often patients affected by these diseases as the skin lesions of the 2 diseases may occur at can be sorted into one of the named CTDs such as separate locations or coexistent disease may develop LE, rheumatoid arthritis, scleroderma, polymyositis/ in the same location, as in our case.

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A B

Figure 2. Interface changes, basement membrane thickening, and periadnexal inflammation supporting a diagnosis of discoid lupus erythematosus (A)(H&E, original magnification ×10). Sclerosis of the reticular dermis with thickening of collagen bundles consistent with localized scleroderma also were notedcopy (B)(H&E, original magnification ×40).

not More than 100 cases have been reported wherein scleroderma to localized scleroderma, suggesting that LE and scleroderma coexist in the same patient.1 localized scleroderma was the end result of persistent Most of these cases have been examples of type 1 inflammation from the cutaneous LE lesions. The overlap (Table 1), though a few have been typeDo 2 investigators compared the evolution of subacute overlap, with localized scleroderma coexisting with cutaneous LE to localized scleroderma in the patient systemic LE or vice versa.1,2 There are rare reports to the evolution of acute graft-versus-host disease of an overlap of the localized form of both of these entities (type 3 overlap), as demonstrated in our patient. According to a PubMed search of articles indexed for MEDLINE using the search terms local- Table 1. ized scleroderma and morphea as well as discoid lupus erythematosus, we found 12CUTIS other cases describing Dermatologic Classification of type 3 overlap (Table 2). Overlap Syndromes in The first case was described in 1976 as annu- Connective-Tissue Diseases lar atrophic plaques on the face and neck of a 48-year-old man.3 As in our case, there were over- Type 1 Systemic disease overlapping with lapping features of DLE and localized scleroderma. systemic disease The investigators postulated that the entity was Type 2 Cutaneous disease (eg, localized an atypical form of DLE.3 There were 4 more cases scleroderma, cutaneous LE) overlapping with described in 1978, but the majority of these patients systemic disease (eg, systemic LE) were young women with linear plaques. Instead of Type 3 Cutaneous disease (eg, localized calling the disease a new form of DLE, the inves- scleroderma) overlapping with cutaneous tigators considered it to be an overlap syndrome.4 disease (eg, cutaneous LE); overlap may occur with distinctive lesions developing at Many years passed before another similar case was separate sites or clinical and/or histological described in the literature in 1990.5 Interestingly, features of both diseases within the same site the investigators performed multiple biopsies on (known as coincident overlap)

this patient over several years and observed that the Abbreviation: LE, lupus erythematosus. pathology changed from subacute cutaneous LE to an overlap of subacute cutaneous LE and localized

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ovement Improvement response Improvement Poor response response Unknown Improvement Impr Improvement Improvement Unknown

IgM, fibrin at DEJ Negative Poor Not reported Not reported Negative Poor IgG, C3 at DEJ Not reported IgM, C3 at DEJ IgM at DEJ Improvement at DEJ IgG, IgM, C3 at DEJ IgG, IgA, IgM at DEJ IgM, C3 Negative Improvement No No No No No renal Yes, No Yes, Yes, oral ulcers Systemic Involvement DIF Evolution No Yes, Yes, thrombocytopenia

None ANA, dsDNA No None None ANA, dsDNA, low C3 ANA, anticardiolipin antibodies ANA ANA, RF, ANA, RF, low C3 Positive Laboratory Results Test None ANA, SS-A No copy Antimalarials None antimalarials antimalarials antimalarials Prednisone, Prednisone, antimalarials Unknown antimalarials Antimalarials, topical steroids Antimalarials Anti-DNA Topical/oral No steroids Topical steroids, steroids, Topical antimalarials not mycophenolate mofetil Do Plaques abx, Steroids, Linear steroids, Topical Linear, Linear, nodules Annular plaques Linear Prednisone, Annular plaques Linear steroids, Topical nodules Linear plaques Linear and annular plaques Annular plaques Plaques steroids, Topical Morphology Therapy a s Yes Yes Yes Yes Yes Yes Yes No Plaques, Yes Yes Ye Yes osis

CUTIS morphea DLE, fibrosis panniculitis, fibrosis appendages Lupus panniculitis DLE, sclerosis No Linear Antimalarials None DLE, sclerosis DLE, sclerosis Histologic Findings Overlap SCLE initially, SCLE initially, then Scleroderma, Scleroderma, lupus panniculitis DLE, sclerosis on repeat biopsy DLE, scler DLE, sclerosis

back Scalp, forehead, buttocks face, arms arms, legs Location Location of Lesions neck, face Arms,breasts, buttocks, face face, arms Face, neck, upper back

b 26 Face, trunk, 40s Age at Onset, y F 11 Scalp, F 20 Arms DLE, morphea F 13 Arms, chest, F 29 Arms Lupus M 48 Face, neck DLE, atrophic F 22 Chest, arms, F 21 F M 47 Face, back, M 34 Forehead DLE, morphea F 22 F 7 Arms

6 (2011) (2011) (2008) (1976) (1990) (2005) 8 9 10 3 5 7 Patient was aged 60 years at presentation, but age of onset was 20–30 years prior, according to the patient. according but age of onset was 20–30 years prior, Patient was aged 60 years at presentation, Overlap occurs in same anatomic location/same clinical site. Rao Rao Current caseCurrent M 30s to Abbreviations: DIF, direct immunofluorescence; M, male; DLE, discoid lupus erythematosus; DEJ, dermoepidermal junction; F, female; SCLE, subacute cutaneous lupus erythematosus; ANA, antinuclear antibody; M, male; DLE, discoid lupus erythematosus; DEJ, dermoepidermal junction; F, immunofluorescence; direct DIF, Abbreviations: antigen A. syndrome rheumatoid factor; dsDNA, double-stranded DNA; abx, antibiotics; SS-A, anti–Sjögren RF, a b Reference Reference (Year) Sex et al Khelifa et al Mir et al Umbert and Winkelmann Julia et al (1994) Marzano et al et al Stork and Vosmik (1978) Chorzelski Table 2. 2. Table 3 Overlap of Connective-Tissue Diseases Summary of Reported Cases Type

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(GVHD) to chronic GVHD. Acute GVHD has a Conclusion lichenoid tissue reaction that develops into sclerosis All 12 previously reported cases showed some form of in the chronic form.5 overlap of cutaneous LE and localized scleroderma. Additionally, there were 3 cases in the lit- As previously discussed, overlap syndromes are com- erature showing an overlap of lupus panniculitis mon in patients with CTDs. We postulate that our with localized scleroderma.6,7 Stork and Vosmik6 case represents a rare form of overlap syndrome, with described a case of a 22-year-old woman with lesions the overlap occurring at the same clinical sites. clinically suspicious for localized scleroderma, with lupus panniculitis demonstrated on histopathol- REFERENCES ogy. They discussed the difficulty in differentiating 1. Iaccarino L, Gatto M, Bettio S, et al. Overlap connective between lupus panniculitis and localized sclero- tissue disease syndromes [published online June 26, 2012]. derma but did not specify whether they believed Autoimmun Reviews. 2012;12:363-373. the case represented a distinct entity or an overlap 2. Balbir-Gurman A, Braun-Moscovici Y. Scleroderma over- syndrome.6 Alternatively, Marzano et al7 reported lap syndrome. Isr Med Assoc J. 2011;13:14-20. 2 similar cases, which the investigators considered to 3. Chorzelski TP, Jablonska S, Blaszyczyk M, et al. be a specific new variant called sclerodermic linear Annular atrophic plaques of the face. Arch Dermatol. lupus panniculitis. 1976;112:1143-1145. In the last 10 years, there were 3 additional cases 4. Umbert P, Winkelmann RK. Concurrent localized sclero- reported that described an overlap of DLE and local- derma and discoid lupus erythematosus. Arch Dermatol. ized scleroderma in the same anatomic location, 1978;114:1473-1478. similar to our patient.8-10 Although Julia et al8 con- 5. Rao BK, Coldiron B, Freeman RG, et al. Subacute cutane- sidered their case to be an example of the distinct ous lupus progressingcopy to morphea erythematosus lesions. entity called sclerodermiform linear LE, the investi- J Am Acad Dermatol. 1990;23(5, pt 2):1019-1022. gators in the other 2 cases described the possibility of 6. Stork J, Vosmik F. Lupus erythematosus panniculitis with an overlap syndrome.9,10 morphea-like lesions. Clin Exp Dermatol. 1994;19:79-82. Based on reported cases, we found the following 7. not Marzano A V, Tanzi C, Caputo R, et al. Sclerodermic patterns in the overlap of cutaneous LE and local- linear lupus panniculitis: report of two cases. Dermatology. ized scleroderma: predilection for young women, 2005;210:329-332. photodistributed lesions, DLE, linear morphology 8. Julia M, Mascaro JM Jr, Guilaber A, et al. Sclerodermiform clinically, and positivity along the dermoepidermalDo linear lupus erythematosus: a distinct entity or coexis- junction on direct immunofluorescence. As in our tence of two autoimmune diseases? J Am Acad Dermatol. case, the few affected men were older compared 2008;58:665-667. to affected women. Men ranged in age from 34 to 9. Mir A, Tlougan B, O’Reilly K, et al. Morphea with discoid 48 years compared to women who ranged in age from lupus erythematosus. Dermatol Online J. 2011;17:10. 7 to 29 years. We did not find a pattern in the labo- 10. Khelifa E, Masouye I, Pham HC, et al. Linear sclero- ratory findings in these patients. Most patients had dermic lupus erythematosus, a distinct variant of linear a good response to antimalarials, topical steroids, or morphea and chronic cutaneous lupus erythematosus. Int J systemic steroids. CUTIS Dermatol. 2011;50:1491-1495.

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