- Email: [email protected]
Lupus tumidus
Lupus tumidus Catherine L. Dekle, MD,a Keith D. Mannes, MD,b Loretta S. Davis, MD,a and Omar P. Sangueza, MDa,b Augusta, Georgia Lupus tumidus is a rare subtype of chronic cutaneous lupus erythematosus that was first described by Gougerot and Bournier in 1930. Clinically, lupus tumidus presents as smooth, shiny, red-violet plaques of the head and neck that may be pruritic and have a fine scale. These lesions characteristically clear without scarring and recur in their original distribution. Histologic features include superficial and deep lymphohistiocytic infiltrates and abundant dermal deposits of mucin. We describe lupus tumidus as a distinct form of cutaneous lupus erythematosus and report 4 cases. (J Am Acad Dermatol 1999;41:250-3.)
L
upus tumidus (LT) is a distinct variety of chronic cutaneous lupus erythematosus that occurs with much less frequency than other forms of cutaneous lupus. Its hallmark clinical features, first described by Gougerot and Bournier in 1930,1 are smooth, shiny, red-violet plaques of the head and neck that can be mildly pruritic and occasionally manifest fine scale. The plaques often clear spontaneously without leaving scars and then recur in the original distribution, leading Gougerot to give the disorder the sobriquet “the eclipse.” Histologically, the tumid form of lupus presents with superficial and deep perivascular lymphohistiocytic infiltrates and abundant mucinous deposits in the reticular dermis. Alteration of the dermoepidermal junction and epidermis is frequently subtle or absent. Because LT has been infrequently reported and usually as only isolated cases, we have collected and retrospectively analyzed 4 cases of the disorder. The clinical, laboratory, and histopathologic features of these cases are presented in this article.
MATERIAL AND METHODS The files of the Medical College of Georgia Section of Dermatology from 1990 to 1997 were reviewed and 4 cases of LT were retrieved. At least 1 skin biopsy specimen was obtained from each of the 4 patients; in 2 cases multiple biopsies were performed (cases 1 and 3). Specimens were fixed in 10% buffered formalin, paraffin embedded, and routinely processed. Multiple sections were stained with hematoxylin and eosin and colloidal iron. Additionally, a
From the Departments of Medicinea and Pathology,b Medical College of Georgia. Reprint requests: Omar P. Sangueza, MD, Department of Pathology, BAE 210, Medical College of Georgia, 1120 15th St, Augusta, GA 30912. Copyright © 1999 by the American Academy of Dermatology, Inc. 0190-9622/99/$8.00 + 0 16/1/97692
250
skin biopsy specimen from patient 1 was snap frozen and multiple 4-µm sections were stained with a series of antibodies (BioWhitaker, Walkersville, Md) against IgG, IgM, IgA, and the third component complement (C3) using the standard direct immunofluorescence technique.
RESULTS Clinical findings Patient 1. A 31-year-old white man presented to his dermatologist with an eruption of the head and neck. The eruption initially cleared after a short course of prednisone, then recurred as plaques on the face, neck, and trunk. The patient was referred to our clinic after experiencing relapse while receiving dapsone and prednisone for presumed Sweet’s syndrome. On presentation, the patient had multiple, pruritic, welldemarcated, red-violet plaques with raised borders of the face, neck, and arms that on subsequent visits also involved the back and upper chest. The lesions were noted to have fine scale and central clearing on some visits. The eruption was more pronounced in sunexposed areas. An antinuclear antibody (ANA) test using human (HEp-2) cells was weakly positive, speckled, with nucleolar distribution; and the antiextractable nuclear antigen (anti-ENA) antibodies SS-A (anti-Ro) and SS-B (anti-LA) were not detected. After an unsuccessful trial of minocycline, the patient was started on a regimen of hydroxychloroquine sulfate 200 mg twice daily, topical steroids, and sunscreens that resulted in some improvement. Patient 2. A 25-year-old black man complained of a 7-month history of “insect bites” of the arms and back that were occasionally pruritic and would not clear. The patient was seen by an outside physician who noted cervical lymphadenopathy and nodular skin lesions and performed biopsies of both. The patient was then referred to our clinic where he presented with hypopigmented macules and plaques
J AM A C A D D ERMATOL V OLUME 41, NUMBER 2, PART 1
Dekle et al 251
Fig 1. Lupus tumidus. Hypopigmented macules and plaques with fine scale on arm (patient 2).
with mild scale distributed on the arms and lower back (Fig 1). No hypoesthesia was noted. The patient was in good health and denied systemic symptoms. Angiotensin-converting enzyme levels were within normal limits. Human cell substrate ANA and rheumatoid factor were negative. Among the extractable nuclear antigens, SS-A was negative; SS-B was equivocal and anti-Smith antibodies were positive at 1:100. Hydroxychloroquine sulfate therapy was initiated but discontinued on appearance of leukopenia. The patient noted some spontaneous clearing of his eruption before being treated with flurandrenolide tape. Patient 3. A 29-year-old white woman with psoriasis experienced well-defined, pruritic, round to oval, erythematous plaques with occasional fine scale located on the malar region and upper arms. These lesions would come and go without scarring and were exacerbated by sun exposure. The plaques remitted with topical corticosteroids before recurring in the same distribution the following summer. A further flare involved the upper chest as well as the face and arms. ANA was 1+ positive, speckled pattern, negative for centromeres, both initially and at recurrence. SS-A and SS-B were negative. The patient noted substantial improvement with hydroxychloroquine sulfate and sunscreens. Patient 4. A 69-year-old white woman presented with a 5-month history of an eruption that began on her upper arms and chest with subsequent involvement of the face and back. Medical history was significant for hypertension, peptic ulcer disease, and osteoarthritis. Skin examination revealed multiple
pink papules and annular plaques without scale over the upper chest, arms, and back. There was one small plaque on the forehead and one on the right side of the jaw line. An ANA test was negative. Within 10 days of beginning betamethasone dipropionate ointment therapy to the individual lesions, the patient noted marked improvement with clearing of the lesions on the arms and flattening of the papules and plaques on the back. Of note, the patient’s facial lesions cleared without therapy. Histopathologic findings All biopsy specimens from the 4 patients had similar features, demonstrating superficial and deep perivascular lymphohistiocytic infiltrates with abundant mucin in the dermis (Fig 2). Periadnexal infiltrates were frequently noted as well. Changes at the dermoepidermal interface, however, were not a constant feature, even among serial biopsy specimens from the same patient. The initial biopsy specimen from patient 1 showed the typical changes of LT, with epidermal involvement limited to only a few scattered dyskeratotic keratinocytes. On repeat biopsy 9 months later, however, he exhibited all of the hallmark features of discoid lupus erythematosus (DLE), including marked vacuolar change of the dermoepidermal junction, perivascular and perifollicular lymphohistiocytic infiltrates, and increased amounts of mucin in the reticular dermis (Fig 3). The direct immunofluorescence on a skin biopsy specimen from patient 1 obtained from a nonlesional sun-protected area showed granular deposits of IgG and C3 along the basement membrane.
252 Dekle et al
A
J AM A C A D D ERMATOL A UGUST 1999
B Fig 2. Lupus tumidus. A, Scanning magnification showing superficial and deep infiltrates and increased amounts of mucin within dermis. Epidermis demonstrates focal areas of parakeratosis. B, Detail of mucin separating collagen bundles.
DISCUSSION LT is an unusual clinical variant of chronic cutaneous lupus erythematosus. In a 1987 study of lupus patients treated at the Dusseldorf Department of Dermatology, this form of lupus was reported to be “exceptional.”2 Other authors attest to the rarity of this variant.3 We agree that this unusual presentation is an authentic and distinct subtype of chronic cutaneous lupus erythematosus. Clinically, the sharply demarcated, smooth, shiny, red-violet, pruritic plaques of LT, with its characteristic distribution on the face and neck, are consistent with several disease processes of both infectious and inflammatory origin. When fine scale is present, tinea facialis and corporis become considerations, although these can easily be distinguished with potassium hydroxide examination. Other papulosquamous diseases such as psoriasis, pityriasis rosea, pityriasis rubra pilaris, and pityriasis lichenoides may be a consideration in the differential diagnosis of LT. However, the lack of epidermal changes in LT facilitates the distinction between LT and this other group of diseases. Sarcoidosis is also in the clinical differential diagnosis of LT, but would be easily recognized on histologic examination.
Histopathologically, LT can be categorized as a superficial and deep perivascular lymphohistiocytic dermatitis. However, the diagnosis can be difficult to make because alterations of the dermoepidermal junction are not always pronounced or present at all.3,4 The differential diagnosis for this histologic pattern includes polymorphous light eruption, lymphocytic infiltration of Jessner, deep gyrate erythema, indeterminate leprosy, and lymphocytic leukemia. Of these, lymphohistiocytic infiltration of Jessner may be indistinguishable from LT. In fact, we wonder whether Jessner’s and LT may be the same disease, with Jessner’s representing an earlier form of the disease that, in time, will progress to the full-blown features of LT. Other authors also consider that lymphocytic infiltrate of Jessner is a variant of DLE.5 Other features used to distinguish these entities from each other include presence of edema in the papillary dermis (marked in PMLE and minimal in deep gyrate erythema) and involvement of cutaneous nerves (noted in indeterminate leprosy). Lymphocytic leukemia presents with monomorphous infiltrates of lymphocytes, some of them atypical, without increased amounts of mucin.
J AM A C A D D ERMATOL V OLUME 41, NUMBER 2, PART 1
Dekle et al 253
Fig 3. Lupus tumidus. Second biopsy specimen of patient 1 showing prominent vacuolar changes, increased mucin, and perivascular infiltrates composed mainly of lymphocytes.
There is disagreement as to whether LT presents with scale as do other types of cutaneous lupus. Ackerman4 reports that there is no scale in these lesions, but both the original report by Gougerot and Bournier1 and subsequent authors6 have noted surface changes on some lesions, including scale. One author even described changes akin to Wickham’s striae.3 In our series, 3 patients had fine scale of occasional lesions. The distribution of these lesions is also of interest. Whereas the plaques typically appear initially and primarily on sun-exposed areas, at least 1 author has reported the eventual migration of the lesions to non-sun–exposed areas as well.5 In our series, the arms and trunk were the most common areas to be affected (4/4), and the sun-exposed areas of the head and neck were the second most common areas of involvement (3/4). The lesions typically appeared first on sun-exposed surfaces, a pattern also noted by other investigators.6 Lower extremities were not involved in any of our cases, and this finding is consistent with previous reports.1,6 From the earliest clinical report of the disease, it was noted that these “atypical” lesions of cutaneous lupus could exist simultaneously with classic DLE.1 In 1 of our 4 cases, the original biopsy specimen showed histopathologic features consistent with LT, then had features more consistent with classic DLE on repeat biopsy 9 months later. These features included the presence of vacuoles at the dermoepidermal junction as well as granular deposits of IgG and C3 along the basement membrane on direct
immunofluorescence. This lends further support to the idea that LT can evolve into typical DLE and is a part of the spectrum of the lesions of cutaneous lupus erythematosus. In conclusion, we report 4 cases of LT, a rare variant of chronic cutaneous lupus erythematosus. Clinical features that distinguish the lesions of LT from DLE are the lack of follicular plugging and the tendency to clear without scarring and then to recur in the initial distribution. This “eclipse” phenomenon described by Gougerot was noted in 3 cases in our series. To our knowledge, LT has not previously been reported in African-Americans. It is unclear whether some of the differences in both distribution (no involvement of the head and neck) and secondary characteristics (hypopigmentation rather than erythema) found in our patient relate to racial background. REFERENCES 1. Gougerot MH, Bournier. Lupus erythematodes tumidus. Bull Soc Fr Derm Syph 1930:1291-2. 2. Kind P, Goerz G. Klinik und differentialdiagnose des cutanen lupus erythematodes. Z Hautkr 1987;62:1337-47. 3. Sontheimer RD, Provost TT. Cutaneous manifestations of lupus erythematosus. In: Wallace DJ, Hannahs BH, editors. Dubois’ Lupus erythematosus. 5th ed. Baltimore: Williams & Wilkins; 1997. p. 594-5. 4. Ackerman AB. Histologic diagnosis of inflammatory skin diseases. 2nd ed. Baltimore: Williams & Wilkins; 1997. p. 525-31. 5. Weyers W, Bonczkowitz M, Weyers I. LE or not LE—that is the question. Am J Dermatopathol 1998;20:225-32. 6. Vieitez JCM, de la Torre C, Prado MJC. Lupus eritematoso tumido de Gougerot. Med Cutan Ibero Lat Am 1984;12:425-9.
L
upus tumidus (LT) is a distinct variety of chronic cutaneous lupus erythematosus that occurs with much less frequency than other forms of cutaneous lupus. Its hallmark clinical features, first described by Gougerot and Bournier in 1930,1 are smooth, shiny, red-violet plaques of the head and neck that can be mildly pruritic and occasionally manifest fine scale. The plaques often clear spontaneously without leaving scars and then recur in the original distribution, leading Gougerot to give the disorder the sobriquet “the eclipse.” Histologically, the tumid form of lupus presents with superficial and deep perivascular lymphohistiocytic infiltrates and abundant mucinous deposits in the reticular dermis. Alteration of the dermoepidermal junction and epidermis is frequently subtle or absent. Because LT has been infrequently reported and usually as only isolated cases, we have collected and retrospectively analyzed 4 cases of the disorder. The clinical, laboratory, and histopathologic features of these cases are presented in this article.
MATERIAL AND METHODS The files of the Medical College of Georgia Section of Dermatology from 1990 to 1997 were reviewed and 4 cases of LT were retrieved. At least 1 skin biopsy specimen was obtained from each of the 4 patients; in 2 cases multiple biopsies were performed (cases 1 and 3). Specimens were fixed in 10% buffered formalin, paraffin embedded, and routinely processed. Multiple sections were stained with hematoxylin and eosin and colloidal iron. Additionally, a
From the Departments of Medicinea and Pathology,b Medical College of Georgia. Reprint requests: Omar P. Sangueza, MD, Department of Pathology, BAE 210, Medical College of Georgia, 1120 15th St, Augusta, GA 30912. Copyright © 1999 by the American Academy of Dermatology, Inc. 0190-9622/99/$8.00 + 0 16/1/97692
250
skin biopsy specimen from patient 1 was snap frozen and multiple 4-µm sections were stained with a series of antibodies (BioWhitaker, Walkersville, Md) against IgG, IgM, IgA, and the third component complement (C3) using the standard direct immunofluorescence technique.
RESULTS Clinical findings Patient 1. A 31-year-old white man presented to his dermatologist with an eruption of the head and neck. The eruption initially cleared after a short course of prednisone, then recurred as plaques on the face, neck, and trunk. The patient was referred to our clinic after experiencing relapse while receiving dapsone and prednisone for presumed Sweet’s syndrome. On presentation, the patient had multiple, pruritic, welldemarcated, red-violet plaques with raised borders of the face, neck, and arms that on subsequent visits also involved the back and upper chest. The lesions were noted to have fine scale and central clearing on some visits. The eruption was more pronounced in sunexposed areas. An antinuclear antibody (ANA) test using human (HEp-2) cells was weakly positive, speckled, with nucleolar distribution; and the antiextractable nuclear antigen (anti-ENA) antibodies SS-A (anti-Ro) and SS-B (anti-LA) were not detected. After an unsuccessful trial of minocycline, the patient was started on a regimen of hydroxychloroquine sulfate 200 mg twice daily, topical steroids, and sunscreens that resulted in some improvement. Patient 2. A 25-year-old black man complained of a 7-month history of “insect bites” of the arms and back that were occasionally pruritic and would not clear. The patient was seen by an outside physician who noted cervical lymphadenopathy and nodular skin lesions and performed biopsies of both. The patient was then referred to our clinic where he presented with hypopigmented macules and plaques
J AM A C A D D ERMATOL V OLUME 41, NUMBER 2, PART 1
Dekle et al 251
Fig 1. Lupus tumidus. Hypopigmented macules and plaques with fine scale on arm (patient 2).
with mild scale distributed on the arms and lower back (Fig 1). No hypoesthesia was noted. The patient was in good health and denied systemic symptoms. Angiotensin-converting enzyme levels were within normal limits. Human cell substrate ANA and rheumatoid factor were negative. Among the extractable nuclear antigens, SS-A was negative; SS-B was equivocal and anti-Smith antibodies were positive at 1:100. Hydroxychloroquine sulfate therapy was initiated but discontinued on appearance of leukopenia. The patient noted some spontaneous clearing of his eruption before being treated with flurandrenolide tape. Patient 3. A 29-year-old white woman with psoriasis experienced well-defined, pruritic, round to oval, erythematous plaques with occasional fine scale located on the malar region and upper arms. These lesions would come and go without scarring and were exacerbated by sun exposure. The plaques remitted with topical corticosteroids before recurring in the same distribution the following summer. A further flare involved the upper chest as well as the face and arms. ANA was 1+ positive, speckled pattern, negative for centromeres, both initially and at recurrence. SS-A and SS-B were negative. The patient noted substantial improvement with hydroxychloroquine sulfate and sunscreens. Patient 4. A 69-year-old white woman presented with a 5-month history of an eruption that began on her upper arms and chest with subsequent involvement of the face and back. Medical history was significant for hypertension, peptic ulcer disease, and osteoarthritis. Skin examination revealed multiple
pink papules and annular plaques without scale over the upper chest, arms, and back. There was one small plaque on the forehead and one on the right side of the jaw line. An ANA test was negative. Within 10 days of beginning betamethasone dipropionate ointment therapy to the individual lesions, the patient noted marked improvement with clearing of the lesions on the arms and flattening of the papules and plaques on the back. Of note, the patient’s facial lesions cleared without therapy. Histopathologic findings All biopsy specimens from the 4 patients had similar features, demonstrating superficial and deep perivascular lymphohistiocytic infiltrates with abundant mucin in the dermis (Fig 2). Periadnexal infiltrates were frequently noted as well. Changes at the dermoepidermal interface, however, were not a constant feature, even among serial biopsy specimens from the same patient. The initial biopsy specimen from patient 1 showed the typical changes of LT, with epidermal involvement limited to only a few scattered dyskeratotic keratinocytes. On repeat biopsy 9 months later, however, he exhibited all of the hallmark features of discoid lupus erythematosus (DLE), including marked vacuolar change of the dermoepidermal junction, perivascular and perifollicular lymphohistiocytic infiltrates, and increased amounts of mucin in the reticular dermis (Fig 3). The direct immunofluorescence on a skin biopsy specimen from patient 1 obtained from a nonlesional sun-protected area showed granular deposits of IgG and C3 along the basement membrane.
252 Dekle et al
A
J AM A C A D D ERMATOL A UGUST 1999
B Fig 2. Lupus tumidus. A, Scanning magnification showing superficial and deep infiltrates and increased amounts of mucin within dermis. Epidermis demonstrates focal areas of parakeratosis. B, Detail of mucin separating collagen bundles.
DISCUSSION LT is an unusual clinical variant of chronic cutaneous lupus erythematosus. In a 1987 study of lupus patients treated at the Dusseldorf Department of Dermatology, this form of lupus was reported to be “exceptional.”2 Other authors attest to the rarity of this variant.3 We agree that this unusual presentation is an authentic and distinct subtype of chronic cutaneous lupus erythematosus. Clinically, the sharply demarcated, smooth, shiny, red-violet, pruritic plaques of LT, with its characteristic distribution on the face and neck, are consistent with several disease processes of both infectious and inflammatory origin. When fine scale is present, tinea facialis and corporis become considerations, although these can easily be distinguished with potassium hydroxide examination. Other papulosquamous diseases such as psoriasis, pityriasis rosea, pityriasis rubra pilaris, and pityriasis lichenoides may be a consideration in the differential diagnosis of LT. However, the lack of epidermal changes in LT facilitates the distinction between LT and this other group of diseases. Sarcoidosis is also in the clinical differential diagnosis of LT, but would be easily recognized on histologic examination.
Histopathologically, LT can be categorized as a superficial and deep perivascular lymphohistiocytic dermatitis. However, the diagnosis can be difficult to make because alterations of the dermoepidermal junction are not always pronounced or present at all.3,4 The differential diagnosis for this histologic pattern includes polymorphous light eruption, lymphocytic infiltration of Jessner, deep gyrate erythema, indeterminate leprosy, and lymphocytic leukemia. Of these, lymphohistiocytic infiltration of Jessner may be indistinguishable from LT. In fact, we wonder whether Jessner’s and LT may be the same disease, with Jessner’s representing an earlier form of the disease that, in time, will progress to the full-blown features of LT. Other authors also consider that lymphocytic infiltrate of Jessner is a variant of DLE.5 Other features used to distinguish these entities from each other include presence of edema in the papillary dermis (marked in PMLE and minimal in deep gyrate erythema) and involvement of cutaneous nerves (noted in indeterminate leprosy). Lymphocytic leukemia presents with monomorphous infiltrates of lymphocytes, some of them atypical, without increased amounts of mucin.
J AM A C A D D ERMATOL V OLUME 41, NUMBER 2, PART 1
Dekle et al 253
Fig 3. Lupus tumidus. Second biopsy specimen of patient 1 showing prominent vacuolar changes, increased mucin, and perivascular infiltrates composed mainly of lymphocytes.
There is disagreement as to whether LT presents with scale as do other types of cutaneous lupus. Ackerman4 reports that there is no scale in these lesions, but both the original report by Gougerot and Bournier1 and subsequent authors6 have noted surface changes on some lesions, including scale. One author even described changes akin to Wickham’s striae.3 In our series, 3 patients had fine scale of occasional lesions. The distribution of these lesions is also of interest. Whereas the plaques typically appear initially and primarily on sun-exposed areas, at least 1 author has reported the eventual migration of the lesions to non-sun–exposed areas as well.5 In our series, the arms and trunk were the most common areas to be affected (4/4), and the sun-exposed areas of the head and neck were the second most common areas of involvement (3/4). The lesions typically appeared first on sun-exposed surfaces, a pattern also noted by other investigators.6 Lower extremities were not involved in any of our cases, and this finding is consistent with previous reports.1,6 From the earliest clinical report of the disease, it was noted that these “atypical” lesions of cutaneous lupus could exist simultaneously with classic DLE.1 In 1 of our 4 cases, the original biopsy specimen showed histopathologic features consistent with LT, then had features more consistent with classic DLE on repeat biopsy 9 months later. These features included the presence of vacuoles at the dermoepidermal junction as well as granular deposits of IgG and C3 along the basement membrane on direct
immunofluorescence. This lends further support to the idea that LT can evolve into typical DLE and is a part of the spectrum of the lesions of cutaneous lupus erythematosus. In conclusion, we report 4 cases of LT, a rare variant of chronic cutaneous lupus erythematosus. Clinical features that distinguish the lesions of LT from DLE are the lack of follicular plugging and the tendency to clear without scarring and then to recur in the initial distribution. This “eclipse” phenomenon described by Gougerot was noted in 3 cases in our series. To our knowledge, LT has not previously been reported in African-Americans. It is unclear whether some of the differences in both distribution (no involvement of the head and neck) and secondary characteristics (hypopigmentation rather than erythema) found in our patient relate to racial background. REFERENCES 1. Gougerot MH, Bournier. Lupus erythematodes tumidus. Bull Soc Fr Derm Syph 1930:1291-2. 2. Kind P, Goerz G. Klinik und differentialdiagnose des cutanen lupus erythematodes. Z Hautkr 1987;62:1337-47. 3. Sontheimer RD, Provost TT. Cutaneous manifestations of lupus erythematosus. In: Wallace DJ, Hannahs BH, editors. Dubois’ Lupus erythematosus. 5th ed. Baltimore: Williams & Wilkins; 1997. p. 594-5. 4. Ackerman AB. Histologic diagnosis of inflammatory skin diseases. 2nd ed. Baltimore: Williams & Wilkins; 1997. p. 525-31. 5. Weyers W, Bonczkowitz M, Weyers I. LE or not LE—that is the question. Am J Dermatopathol 1998;20:225-32. 6. Vieitez JCM, de la Torre C, Prado MJC. Lupus eritematoso tumido de Gougerot. Med Cutan Ibero Lat Am 1984;12:425-9.