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

Although lupus erythematosus (LE) and scleroderma are regarded as 2 distinct entities, there have been multiple cases described in the literature showing an overlap between these 2 disease processes. We report the case of a 60-year-old man with clinical and histopathologic findings consistent with the presence of localized scleroderma and discoid LE (DLE) within the same lesions. We also present a review of the literature and delineate the general patterns of coexistence of these 2 diseases based on our case and other reported cases.

Case Report

A 60-year-old man presented with a progressive pruritic rash on the face, neck, and upper back of approximately 20 to 30 years’ duration. On initial 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 on the left cheek and upper back. Histopathology was notable for vacuolar interface dermatitis with dermal sclerosis at both sites. Specifically, interface changes, basement membrane thickening, and periadnexal inflammation were present on histopathologic examination from both biopsies supporting a diagnosis of DLE (Figure 2A). However, there also was sclerosis present in the reticular dermis, suggesting a diagnosis of localized scleroderma (Figure 2B). Direct immunofluorescence was negative for a lupus band. Laboratory workup was positive for antinuclear antibody (titer, 1:40; speckled pattern) and anti–Sjögren syndrome antigen A but negative for double-stranded DNA antibody, anti-Smith antibody, anti–Sjögren syndrome antigen B, and Scl-70.

The patient was started on oral hydroxychloroquine 200 mg twice daily and clobetasol oint-ment 0.05% twice daily to affected areas. After 2 weeks of treatment, he developed urticaria on the trunk and the hydroxychloroquine was discontinued. He continued using only topical steroids following a regimen of applying clobetasol ointment 0.05% twice daily for 2 weeks, alternating with the use of triamcinolone ointment 0.1% twice daily for 2 weeks with improvement of the pruritus, but the induration and hypopigmentation remained unchanged. Alternative systemic medication was started with mycophenolate mofetil 1 g twice daily. The patient showed remarkable clinical improvement with a decrease in induration and partial resolution of follicular plugging after 4 months of treatment with mycophenolate mofetil in combination with the topical steroid regimen.

Comment

Autoimmune connective-tissue diseases (CTDs) often occur with a wide range of symptoms and signs. Most often patients affected by these diseases can be sorted into one of the named CTDs such as LE, rheumatoid arthritis, scleroderma, polymyositis/dermatomyositis, and Sjögren syndrome. On the other hand, it is widely recognized that patients with one classic autoimmune CTD are likely to possess multiple autoantibodies, and a small number of these patients develop symptoms and/or signs that satisfy the diagnostic criteria of a second autoimmune CTD; these latter patients are said to have an overlap syndrome.¹ The development of a second identifiable CTD, hence indicating an overlap syndrome, may occur coincident to the initial CTD or may occur at a different time.¹

Essentially all 5 of the CTDs mentioned above have been reported to occur in combination with one another. Most of the reports involving overlap among these 5 CTDs include patients with multiorgan systemic involvement without cutaneous involvement, leading to a fairly simple straightforward classification of overlap syndromes as viewed by rheumatologists.¹

When the overlap occurs between the localized forms of scleroderma and purely cutaneous LE, the situation becomes even more complicated, as the skin lesions of the 2 diseases may occur at separate locations or coexistent disease may develop in the same location, as in our case.

More than 100 cases have been reported wherein LE and scleroderma coexist in the same patient.¹ Most of these cases have been examples of type 1 overlap (Table 1), though a few have been type 2 overlap, with localized scleroderma coexisting with systemic LE or vice versa.^1,2 There are rare reports 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 localized scleroderma and morphea as well as discoid lupus erythematosus, we found 12 other cases describing type 3 overlap (Table 2).

The first case was described in 1976 as annular atrophic plaques on the face and neck of a 48-year-old man.³ As in our case, there were overlapping features of DLE and localized scleroderma. The investigators postulated that the entity was an atypical form of DLE.³ There were 4 more cases described in 1978, but the majority of these patients were young women with linear plaques. Instead of calling the disease a new form of DLE, the investigators considered it to be an overlap syndrome.⁴ Many years passed before another similar case was described in the literature in 1990.⁵ Interestingly, the investigators performed multiple biopsies on this patient over several years and observed that the pathology changed from subacute cutaneous LE to an overlap of subacute cutaneous LE and localized scleroderma to localized scleroderma, suggesting that localized scleroderma was the end result of persistent inflammation from the cutaneous LE lesions. The investigators compared the evolution of subacute cutaneous LE to localized scleroderma in the patient to the evolution of acute graft-versus-host disease (GVHD) to chronic GVHD. Acute GVHD has a lichenoid tissue reaction that develops into sclerosis in the chronic form.⁵

Additionally, there were 3 cases in the literature showing an overlap of lupus panniculitis with localized scleroderma.^6,7 Stork and Vosmik⁶ described a case of a 22-year-old woman with lesions clinically suspicious for localized scleroderma, with lupus panniculitis demonstrated on histopathology. They discussed the difficulty in differentiating between lupus panniculitis and localized scleroderma but did not specify whether they believed the case represented a distinct entity or an overlap syndrome.⁶ Alternatively, Marzano et al⁷ reported 2 similar cases, which the investigators considered to be a specific new variant called sclerodermic linear lupus panniculitis.

In the last 10 years, there were 3 additional cases reported that described an overlap of DLE and localized scleroderma in the same anatomic location, similar to our patient.^8-10 Although Julia et al⁸ considered their case to be an example of the distinct entity called sclerodermiform linear LE, the investigators in the other 2 cases described the possibility of an overlap syndrome.^9,10

Based on reported cases, we found the following patterns in the overlap of cutaneous LE and localized scleroderma: predilection for young women, photodistributed lesions, DLE, linear morphology clinically, and positivity along the dermoepidermal junction on direct immunofluorescence. As in our case, the few affected men were older compared to affected women. Men ranged in age from 34 to 48 years compared to women who ranged in age from 7 to 29 years. We did not find a pattern in the laboratory findings in these patients. Most patients had a good response to antimalarials, topical steroids, or systemic steroids.

Conclusion

All 12 previously reported cases showed some form of overlap of cutaneous LE and localized scleroderma. As previously discussed, overlap syndromes are common in patients with CTDs. We postulate that our case represents a rare form of overlap syndrome, with the overlap occurring at the same clinical sites.

Although lupus erythematosus (LE) and scleroderma are regarded as 2 distinct entities, there have been multiple cases described in the literature showing an overlap between these 2 disease processes. We report the case of a 60-year-old man with clinical and histopathologic findings consistent with the presence of localized scleroderma and discoid LE (DLE) within the same lesions. We also present a review of the literature and delineate the general patterns of coexistence of these 2 diseases based on our case and other reported cases.

Case Report

A 60-year-old man presented with a progressive pruritic rash on the face, neck, and upper back of approximately 20 to 30 years’ duration. On initial 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 on the left cheek and upper back. Histopathology was notable for vacuolar interface dermatitis with dermal sclerosis at both sites. Specifically, interface changes, basement membrane thickening, and periadnexal inflammation were present on histopathologic examination from both biopsies supporting a diagnosis of DLE (Figure 2A). However, there also was sclerosis present in the reticular dermis, suggesting a diagnosis of localized scleroderma (Figure 2B). Direct immunofluorescence was negative for a lupus band. Laboratory workup was positive for antinuclear antibody (titer, 1:40; speckled pattern) and anti–Sjögren syndrome antigen A but negative for double-stranded DNA antibody, anti-Smith antibody, anti–Sjögren syndrome antigen B, and Scl-70.

The patient was started on oral hydroxychloroquine 200 mg twice daily and clobetasol oint-ment 0.05% twice daily to affected areas. After 2 weeks of treatment, he developed urticaria on the trunk and the hydroxychloroquine was discontinued. He continued using only topical steroids following a regimen of applying clobetasol ointment 0.05% twice daily for 2 weeks, alternating with the use of triamcinolone ointment 0.1% twice daily for 2 weeks with improvement of the pruritus, but the induration and hypopigmentation remained unchanged. Alternative systemic medication was started with mycophenolate mofetil 1 g twice daily. The patient showed remarkable clinical improvement with a decrease in induration and partial resolution of follicular plugging after 4 months of treatment with mycophenolate mofetil in combination with the topical steroid regimen.

Comment

Autoimmune connective-tissue diseases (CTDs) often occur with a wide range of symptoms and signs. Most often patients affected by these diseases can be sorted into one of the named CTDs such as LE, rheumatoid arthritis, scleroderma, polymyositis/dermatomyositis, and Sjögren syndrome. On the other hand, it is widely recognized that patients with one classic autoimmune CTD are likely to possess multiple autoantibodies, and a small number of these patients develop symptoms and/or signs that satisfy the diagnostic criteria of a second autoimmune CTD; these latter patients are said to have an overlap syndrome.¹ The development of a second identifiable CTD, hence indicating an overlap syndrome, may occur coincident to the initial CTD or may occur at a different time.¹

Essentially all 5 of the CTDs mentioned above have been reported to occur in combination with one another. Most of the reports involving overlap among these 5 CTDs include patients with multiorgan systemic involvement without cutaneous involvement, leading to a fairly simple straightforward classification of overlap syndromes as viewed by rheumatologists.¹

When the overlap occurs between the localized forms of scleroderma and purely cutaneous LE, the situation becomes even more complicated, as the skin lesions of the 2 diseases may occur at separate locations or coexistent disease may develop in the same location, as in our case.

More than 100 cases have been reported wherein LE and scleroderma coexist in the same patient.¹ Most of these cases have been examples of type 1 overlap (Table 1), though a few have been type 2 overlap, with localized scleroderma coexisting with systemic LE or vice versa.^1,2 There are rare reports 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 localized scleroderma and morphea as well as discoid lupus erythematosus, we found 12 other cases describing type 3 overlap (Table 2).

The first case was described in 1976 as annular atrophic plaques on the face and neck of a 48-year-old man.³ As in our case, there were overlapping features of DLE and localized scleroderma. The investigators postulated that the entity was an atypical form of DLE.³ There were 4 more cases described in 1978, but the majority of these patients were young women with linear plaques. Instead of calling the disease a new form of DLE, the investigators considered it to be an overlap syndrome.⁴ Many years passed before another similar case was described in the literature in 1990.⁵ Interestingly, the investigators performed multiple biopsies on this patient over several years and observed that the pathology changed from subacute cutaneous LE to an overlap of subacute cutaneous LE and localized scleroderma to localized scleroderma, suggesting that localized scleroderma was the end result of persistent inflammation from the cutaneous LE lesions. The investigators compared the evolution of subacute cutaneous LE to localized scleroderma in the patient to the evolution of acute graft-versus-host disease (GVHD) to chronic GVHD. Acute GVHD has a lichenoid tissue reaction that develops into sclerosis in the chronic form.⁵

Additionally, there were 3 cases in the literature showing an overlap of lupus panniculitis with localized scleroderma.^6,7 Stork and Vosmik⁶ described a case of a 22-year-old woman with lesions clinically suspicious for localized scleroderma, with lupus panniculitis demonstrated on histopathology. They discussed the difficulty in differentiating between lupus panniculitis and localized scleroderma but did not specify whether they believed the case represented a distinct entity or an overlap syndrome.⁶ Alternatively, Marzano et al⁷ reported 2 similar cases, which the investigators considered to be a specific new variant called sclerodermic linear lupus panniculitis.

In the last 10 years, there were 3 additional cases reported that described an overlap of DLE and localized scleroderma in the same anatomic location, similar to our patient.^8-10 Although Julia et al⁸ considered their case to be an example of the distinct entity called sclerodermiform linear LE, the investigators in the other 2 cases described the possibility of an overlap syndrome.^9,10

Based on reported cases, we found the following patterns in the overlap of cutaneous LE and localized scleroderma: predilection for young women, photodistributed lesions, DLE, linear morphology clinically, and positivity along the dermoepidermal junction on direct immunofluorescence. As in our case, the few affected men were older compared to affected women. Men ranged in age from 34 to 48 years compared to women who ranged in age from 7 to 29 years. We did not find a pattern in the laboratory findings in these patients. Most patients had a good response to antimalarials, topical steroids, or systemic steroids.

Conclusion

All 12 previously reported cases showed some form of overlap of cutaneous LE and localized scleroderma. As previously discussed, overlap syndromes are common in patients with CTDs. We postulate that our case represents a rare form of overlap syndrome, with the overlap occurring at the same clinical sites.

Although lupus erythematosus (LE) and scleroderma are regarded as 2 distinct entities, there have been multiple cases described in the literature showing an overlap between these 2 disease processes. We report the case of a 60-year-old man with clinical and histopathologic findings consistent with the presence of localized scleroderma and discoid LE (DLE) within the same lesions. We also present a review of the literature and delineate the general patterns of coexistence of these 2 diseases based on our case and other reported cases.

Case Report

A 60-year-old man presented with a progressive pruritic rash on the face, neck, and upper back of approximately 20 to 30 years’ duration. On initial 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 on the left cheek and upper back. Histopathology was notable for vacuolar interface dermatitis with dermal sclerosis at both sites. Specifically, interface changes, basement membrane thickening, and periadnexal inflammation were present on histopathologic examination from both biopsies supporting a diagnosis of DLE (Figure 2A). However, there also was sclerosis present in the reticular dermis, suggesting a diagnosis of localized scleroderma (Figure 2B). Direct immunofluorescence was negative for a lupus band. Laboratory workup was positive for antinuclear antibody (titer, 1:40; speckled pattern) and anti–Sjögren syndrome antigen A but negative for double-stranded DNA antibody, anti-Smith antibody, anti–Sjögren syndrome antigen B, and Scl-70.

The patient was started on oral hydroxychloroquine 200 mg twice daily and clobetasol oint-ment 0.05% twice daily to affected areas. After 2 weeks of treatment, he developed urticaria on the trunk and the hydroxychloroquine was discontinued. He continued using only topical steroids following a regimen of applying clobetasol ointment 0.05% twice daily for 2 weeks, alternating with the use of triamcinolone ointment 0.1% twice daily for 2 weeks with improvement of the pruritus, but the induration and hypopigmentation remained unchanged. Alternative systemic medication was started with mycophenolate mofetil 1 g twice daily. The patient showed remarkable clinical improvement with a decrease in induration and partial resolution of follicular plugging after 4 months of treatment with mycophenolate mofetil in combination with the topical steroid regimen.

Comment

Autoimmune connective-tissue diseases (CTDs) often occur with a wide range of symptoms and signs. Most often patients affected by these diseases can be sorted into one of the named CTDs such as LE, rheumatoid arthritis, scleroderma, polymyositis/dermatomyositis, and Sjögren syndrome. On the other hand, it is widely recognized that patients with one classic autoimmune CTD are likely to possess multiple autoantibodies, and a small number of these patients develop symptoms and/or signs that satisfy the diagnostic criteria of a second autoimmune CTD; these latter patients are said to have an overlap syndrome.¹ The development of a second identifiable CTD, hence indicating an overlap syndrome, may occur coincident to the initial CTD or may occur at a different time.¹

Essentially all 5 of the CTDs mentioned above have been reported to occur in combination with one another. Most of the reports involving overlap among these 5 CTDs include patients with multiorgan systemic involvement without cutaneous involvement, leading to a fairly simple straightforward classification of overlap syndromes as viewed by rheumatologists.¹

When the overlap occurs between the localized forms of scleroderma and purely cutaneous LE, the situation becomes even more complicated, as the skin lesions of the 2 diseases may occur at separate locations or coexistent disease may develop in the same location, as in our case.

More than 100 cases have been reported wherein LE and scleroderma coexist in the same patient.¹ Most of these cases have been examples of type 1 overlap (Table 1), though a few have been type 2 overlap, with localized scleroderma coexisting with systemic LE or vice versa.^1,2 There are rare reports 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 localized scleroderma and morphea as well as discoid lupus erythematosus, we found 12 other cases describing type 3 overlap (Table 2).

The first case was described in 1976 as annular atrophic plaques on the face and neck of a 48-year-old man.³ As in our case, there were overlapping features of DLE and localized scleroderma. The investigators postulated that the entity was an atypical form of DLE.³ There were 4 more cases described in 1978, but the majority of these patients were young women with linear plaques. Instead of calling the disease a new form of DLE, the investigators considered it to be an overlap syndrome.⁴ Many years passed before another similar case was described in the literature in 1990.⁵ Interestingly, the investigators performed multiple biopsies on this patient over several years and observed that the pathology changed from subacute cutaneous LE to an overlap of subacute cutaneous LE and localized scleroderma to localized scleroderma, suggesting that localized scleroderma was the end result of persistent inflammation from the cutaneous LE lesions. The investigators compared the evolution of subacute cutaneous LE to localized scleroderma in the patient to the evolution of acute graft-versus-host disease (GVHD) to chronic GVHD. Acute GVHD has a lichenoid tissue reaction that develops into sclerosis in the chronic form.⁵

Additionally, there were 3 cases in the literature showing an overlap of lupus panniculitis with localized scleroderma.^6,7 Stork and Vosmik⁶ described a case of a 22-year-old woman with lesions clinically suspicious for localized scleroderma, with lupus panniculitis demonstrated on histopathology. They discussed the difficulty in differentiating between lupus panniculitis and localized scleroderma but did not specify whether they believed the case represented a distinct entity or an overlap syndrome.⁶ Alternatively, Marzano et al⁷ reported 2 similar cases, which the investigators considered to be a specific new variant called sclerodermic linear lupus panniculitis.

In the last 10 years, there were 3 additional cases reported that described an overlap of DLE and localized scleroderma in the same anatomic location, similar to our patient.^8-10 Although Julia et al⁸ considered their case to be an example of the distinct entity called sclerodermiform linear LE, the investigators in the other 2 cases described the possibility of an overlap syndrome.^9,10

Based on reported cases, we found the following patterns in the overlap of cutaneous LE and localized scleroderma: predilection for young women, photodistributed lesions, DLE, linear morphology clinically, and positivity along the dermoepidermal junction on direct immunofluorescence. As in our case, the few affected men were older compared to affected women. Men ranged in age from 34 to 48 years compared to women who ranged in age from 7 to 29 years. We did not find a pattern in the laboratory findings in these patients. Most patients had a good response to antimalarials, topical steroids, or systemic steroids.

Conclusion

All 12 previously reported cases showed some form of overlap of cutaneous LE and localized scleroderma. As previously discussed, overlap syndromes are common in patients with CTDs. We postulate that our case represents a rare form of overlap syndrome, with the overlap occurring at the same clinical sites.