Report
Oxford, UK International IJD Blackwell 1365-4632 45 Publishing, Publishing Journal Ltd, of Ltd. Dermatology 2004
Lupus erythematosus tumidus: a series of 26 cases Lupus et Vieira Report erythematosus al. tumidus
Vanessa Vieira, MD, Jesús Del Pozo, MD, Maria Teresa Yebra-Pimentel, MD, Walter Martínez, MD, and Eduardo Fonseca, MD
From the Departments of Dermatology and Pathology, Hospital Juan Canalejo, La Coruña, Spain Correspondence Vanessa Vieira, MD Servicio de Dermatología Hospital Juan Canalejo Xubias de Arriba 84 15006 La Coruña Spain E-mail:
[email protected]
Abstract Objective To study 26 cases of lupus erythematosus tumidus (LET), a subset of chronic cutaneous lupus erythematosus (CCLE), referred to in the literature as a rare entity. Patients and methods A retrospective study was conducted of 26 patients diagnosed with LET between 1996 and 2002. The clinical characteristics, histopathologic and laboratory findings, response to treatment, association with other subsets of lupus, course, and diagnostic criteria were analyzed. Results The incidence by sex was similar. The mean age of presentation was 49.19 years. The clinical presentation usually involved erythematous, edematous plaques located on the face, chest, back, or extremities, related to sun exposure. A dermal lymphocytic infiltrate with a perivascular disposition and differing degrees of mucin deposition was observed in all cases. Minimal epidermal changes were present in 18 cases, and 11 of these also showed minimal dermal–epidermal changes. Only one case showed dermal–epidermal changes without any epidermal alteration. Direct immunofluorescence test was performed in 15 patients, and 11 were negative. All cases showed a benign course without systemic manifestations. The response to topical steroids or antimalarial treatment was excellent, but a seasonal recurrence was usually observed. Discussion No defined criteria for LET are universally accepted. The main controversies are the acceptance of LET as a separate subset of CCLE, and the histopathologic diagnostic features, mainly the presence or absence of epidermal and dermal–epidermal changes in these lesions. Conclusions No inflexible histologic criteria should be employed for the diagnosis of LET. This subset of lupus erythematosus is characterized by intense photosensitivity, definite clinical lesions, a benign course, the absence of systemic disease, good response to antimalarial treatment, and a tendency to recur. More studies should be performed in order to establish the true incidence of LET because this subset of CCLE is probably underestimated.
Introduction
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Gilliam’s classification includes lupus tumidus as a specific lupus erythematosus skin disease a form of chronic cutaneous lupus erythematosus (CCLE) with urticarial plaque morphology.1 Lupus erythematosus tumidus (LET) as a subset of CCLE was described by Gougerot and Burnier in 1930.2 A previous description was possibly given by Hoffman in 1909.3 Some articles on this entity have been published recently. All refer to LET as a rare entity.4–6 Although only a few cases of LET have been described in the literature, there is no reason to consider this entity as a rare disease. Its true prevalence and incidence are unknown and probably have been underestimated. The consideration of LET as a distinct subset of CCLE has been neglected in the literature. Numerous cases of LET have been diagnosed as polymorphic light eruption, Jessner’s International Journal of Dermatology 2006, 45, 512 –517
lymphocytic infiltration of the skin, reticular erythematous mucinosis, pseudolymphoma, subacute cutaneous lupus erythematosus, and other variants of CCLE.7 Kuhn et al.8 recently analyzed the expression of epidermal surface molecules in patients with primary and UV-induced lesions of LET, discoid lupus erythematosus (DLE), and systemic lupus erythematosus (SLE), and concluded that LET is a distinct subset of CCLE. No definitive clinical and histopathologic diagnostic criteria for LET have been accepted. Kuhn et al.6,9 excluded the diagnosis of LET in cases of lupus erythematosus with dermal– epidermal junction or epidermal changes. Nevertheless, Dekle et al.5 considered the diagnosis of LET in cases with minimal changes in the epidermis or the dermal–epidermal junction. We report the clinical and histopathologic characteristics of 26 cases of LET collected and analyzed retrospectively in our hospital. © 2004 The International Society of Dermatology
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Table 1 Diagnostic criteria of lupus erythematosus tumidus in
Materials and Methods
our patients
A retrospective study of 26 cases of LET diagnosed between 1996 and 2002 was conducted at the Dermatology Department of the Juan Canalejo Hospital. The diagnosis of LET was made according to clinical, histologic, and treatment response criteria (Table 1). Thirteen females and 13 males between 18 and 74 years of age (mean, 42.29 years) were included in the study. The main clinical characteristics of our cases are summarized in Table 2. A histopathologic study of lesional skin was performed in all cases (hematoxylin and eosin and Alcian blue stains), and a direct immunofluorescence test in 15. Routine laboratory tests were performed in all cases, antinuclear antibody (ANA) test in 25 cases, and complement levels in 16 cases. The recommended therapy and treatment response were evaluated.
Results Erythematous and edematous plaques without scaling were the most frequent presentation. Two cases showed superficial fine scaling, five a lilac color, three an annular configuration, and two a papular malar eruption (Figs 1–3).
Clinical Erythematous, succulent, urticaria-like, nonscarring papules and plaques with a smooth surface, related to sun exposure Histologic Perivascular and periadnexal lymphocytic infiltrate Interstitial mucin deposition Absence of or minimal epidermal changes Epidermal atrophy Slight vacuolar degeneration of basal cells Slight to moderate hyperkeratosis Follicular plugging Thickening and tortuosity of basal membrane with periodic acid–Schiff (PAS) stain Negative direct immunofluorescence (usually) Analytical Negative serologic tests, e.g. antinuclear antibody (ANA) (usually)
Twenty patients had facial lesions, five lesions on the chest, four on the back, seven on the upper extremities, and one on the lower limbs. Nine patients presented with lesions in several locations, the face and upper extremities being the most frequent.
Table 2 Clinical characteristics of lupus erythematosus tumidus patients
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26
Sex Age Location
Clinical features
Approximate evolution until diagnosis
F F M M F M M M M M M M F F F F M F F F M F M F M F
Erythematous, edematous plaques with superficial scale Erythematous, edematous plaques Erythematous, edematous plaques Erythematous, edematous plaques Erythematous, violaceous, edematous plaques Violaceous plaques with edematous border and annular configuration Erythematous, edematous plaques Erythematous, violaceous, edematous plaques Violaceous, edematous plaques Erythematous, edematous plaques Erythematous, violaceous plaques Erythematous, edematous plaques Erythematous, edematous plaques Erythematous, edematous plaques Erythematous, edematous plaques Malar eruption Erythematous, edematous lesion with annular configuration Malar eruption Erythematous plaques Erythematous papules Erythematous, edematous plaques Erythematous, edematous plaques with superficial scale Erythematous plaques Erythematous edematous plaques Erythematous plaques Erythematous plaques with papulated margins
8 years 5 years 20 months 2 years Several months 1 year 15 days 2 months 3 years 1 year 10 years 13 years 4 years 3 years Years 20 days 1 month Years Years 10 years Years Years 8 years Years 3 days 2 years
71 29 57 38 31 48 49 47 47 74 30 44 42 48 25 18 45 24 26 32 36 25 68 46 45 52
Face Face Back Face, chest Chest Back Chest Face, chest Face Face Face, upper extremities Face, upper extremities Face, upper extremities Face Face Face Face Face Face Face, upper extremities Face, back, upper extremities Face Face, chest, upper extremities Face Upper and lower extremities Chest
© 2004 The International Society of Dermatology
Relationship with sun exposure No Yes No No Yes No Yes Yes No Yes Yes Yes No No Yes Yes No No Yes Yes Yes Yes Yes Yes Yes No
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Figure 2 Multiple confluent lesions on the back
Figure 1 Erythematous and edematous plaque of the face Figure 3 Papular and plaque-like lesions on the face
The interval between the onset of the disease and the confirmation of the diagnosis ranged between 3 and 13 years. This period was usually of several years, and no differences between males and females were observed with regard to the onset of the disease. A clear relationship with solar exposure was found in 16 of the 25 patients. In the remaining patients, this finding was not noted in the history. The interval between sun exposure and eruption development was less than 2 weeks. The histopathologic features are summarized in Table 3. Minimal epidermal changes were found in 18 patients, including epidermal atrophy, slight vacuolar degeneration of basal cells, slight to moderate hyperkeratosis, and follicular plugging (Fig. 4). An enhanced and irregular basal membrane at the dermal–epidermal junction was observed in 11 patients (50%), accompanying epidermal changes. Only one patient had no epidermal changes (Fig. 5). All patients showed a predominantly lymphocytic infiltrate with a perivascular and periadnexal disposition. A variable degree of mucin deposition in the dermis and around the adnexae was demonstrated in all International Journal of Dermatology 2006, 45, 512 –517
patients (Fig. 6). A direct immunofluorescence test was performed in 15 patients, with 11 being negative. Two patients showed slight immunoglobulin G (IgG) deposition at the basal membrane, one had moderate deposition of IgG and slight deposition of C3, and one had slight deposition of IgM, C3, and C1q. Twenty-three patients had normal hemograms. In three, slight anemia, with hemoglobin values around 10 g /dL, was detected. The erythrocyte sedimentation rate was measured in 22 cases: 20 were normal and two showed slight elevation. Twenty-four patients had a negative ANA test. One patient had a positive ANA test at a dilution of 1 : 160 with a homogeneous pattern and negative anti-DNA and anti-ENA (extractable Nuclear Antigen) test. Complement values were determined in 16 patients, with normal values in 11. C4 was decreased in three cases, and C3 and C4 were decreased in two cases. Solar protection was recommended in all patients. The initial pharmacologic treatment with moderate potency topical steroids controlled the symptomatology and cleared the © 2004 The International Society of Dermatology
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Lupus erythematosus tumidus Report
Table 3 Histopathologic features
Epidermal atrophy Slight vacuolar degeneration of basal cells Slight to moderate hyperkeratosis Follicular plugging Enhanced and irregular basal membrane Lymphocytic infiltrate Mucin deposition IgG (DIF) IgM (DIF) C3 (DIF) C1q (DIF)
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– – – –
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No No No No
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No No No No
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No No No No
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No No No No
No No No No
–
DIF, direct immunofluorescence; Ig, immunoglobulin; No, not performed.
Figure 4 Minimal dermal–epidermal changes. Slight
Figure 5 Periodic acid–Schiff (PAS) stain showing slight
perivascular and interstitial dermal lymphocytic infiltrate (hematoxylin and eosin stain, ×40)
thickening of the basal membrane (× 40)
cutaneous lesions in 21 patients. Only five patients required oral antimalarial treatment for control of their cutaneous lesions. The majority of patients had mild recurrences, usually during spring or summer, related to the first sun exposure. These recurrences were successfully controlled with the same treatments. More than 50% of patients remained asymptomatic only with adequate solar protection. © 2004 The International Society of Dermatology
None of the patients developed SLE or other type of CCLE during the course of their disease. Discussion The main difficulty in this study was this variant of CCLE is to define LET. No criteria for this entity have been universally accepted, although several proposals have been made.6,10 Not all authors accept LET as a variant of CCLE. It is possible that International Journal of Dermatology 2006, 45, 512 –517
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Report Lupus erythematosus tumidus
Figure 6 Alcian blue stain showing mucin deposition
intermingled between dermal collagen bundles (×100)
some cases of LET have previously been included as other forms of CCLE, that other variants of CCLE have been diagnosed as LET, and that patients with initial findings compatible with LET have evolved into other variants of CCLE. In addition, some cases of LET may not have been categorized as CCLE and instead diagnosed as other entities, such as reticular erythematous mucinosis or lymphocytic infiltrate of Jessner. In our series, no gender predominance was observed (13 males and 13 females), contrary to Kuhn et al.6 Nevertheless, the sample is too small to make firm conclusions about gender prevalence. Clinically tumid, erythematous and edematous lesions were the predominant presentation. In our patients, similar to Kuhn’s series,6 these lesions did not occur in the context of DLE or SLE, as has been described by other authors.4,10 The relationship with solar exposure was not documented in all patients. This is possibly because the latency period in some cases may last for several weeks after sun exposure. A phototest study performed in 60 patients with LET revealed characteristic skin lesions in 72% of cases.11 Around 50% of cases reacted to UV-A, 50% reacted to UV-B, and 63% reacted to combined UV-A and UV-B. In some cases, specific skin lesions in these phototests appeared up to 4 weeks after the last irradiation. Similar results have been described by Sanders et al.12 in a study of 100 patients with lupus erythematosus. The location of the lesions, relation to solar exposure, common absence of systemic manifestations, response to topical steroids or systemic antimalarial treatment, and tendency to recur were similar in our patients and the cases described in the literature. A key controversial question in LET is the histologic picture. A lymphocytic perivascular and periadnexal infiltrate, International Journal of Dermatology 2006, 45, 512 –517
Vieira et al.
dermal mucin deposition, and often negative direct immunofluorescence test are accepted by the majority of authors. Nevertheless, the possible existence of minimal epidermal and dermal–epidermal junction changes is accepted by some in LET,5,13 and considered as an exclusion criterion by others.4,6,9,14 In our opinion, the existence of minimal epidermal or dermal–epidermal changes accompanying typical dermal findings can be accepted in LET for the following reasons: • The clinical and histopathologic heterogeneity of all subsets of cutaneous lupus erythematosus is evident. • The transition and overlap between several forms of CCLE in the same patient have been reported.4 LET has been described as coexisting or evolving to DLE15 and associated with SLE.16 • Polymorphic light eruption, reticular erythematous mucinosis, and lymphocytic infiltration of the skin17 are considered by some authors as variants of CCLE. The histologic findings of polymorphic light eruption may include minimal epidermal or dermal–epidermal changes.18 • Lehmann et al.19 experimentally reproduced skin lesions of lupus erythematosus with UV-A and UV-B irradiation; they concluded that UV-B possibly has more pronounced effects on the epidermis, because the epidermis absorbs up to 95% of UV-B, whereas UV-A is less damaging to keratinocytes because it penetrates deep into the dermis. Photosensitivity studies in LET have revealed that 50% of cases are induced by UV-B radiation.11,12 • We described a case with initial findings of reticular erythematous mucinosis, without epidermal changes, that developed criteria for SLE. A repeated biopsy performed in the same area revealed the epidermal changes of lupus erythematosus.20 It is possible that the appearance of epidermal and dermal–epidermal changes in patients with LET is altered according to the evolution of the disease. • Sontheimer7 includes LET in a polar extreme of the spectrum of cutaneous histopathologic changes that can be seen in lupus erythematosus-specific skin disease. In this polar extreme, only dermal changes or minimal epidermal changes may be included. • Kuhn’s criteria for LET exclude cases with epidermal or dermal–epidermal alteration. Dermal mucin deposition and a lymphocytic infiltrate are the sole histopathologic changes accepted by this author in LET, but they are not specific diagnostic criteria for lupus. With a less restrictive interpretation, the presence of epidermal and dermal–epidermal alterations, overlying the dermal inflammation and mucin deposition in the majority of patients, supports the classification of LET as a subset of CCLE. In our series, minimal epidermal changes were found in 18 patients and dermal–epidermal changes in 12 patients. The clinical picture of tumid lesions was confirmed, and a benign course was observed. Adequate response to topical steroids and antimalarial treatment was observed. These findings suggest that strict histologic criteria alone cannot be currently employed in the diagnosis of LET. © 2004 The International Society of Dermatology
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Lupus erythematosus tumidus Report
Conclusions In our opinion, LET is a separate variant of CCLE, clinically characterized by erythematous and edematous lesions with marked photosensitivity. The histopathologic picture may include minimal epidermal or dermal–epidermal changes, accompanied by a perivascular and periadnexal inflammatory lymphocytic infiltrate, with the presence of dermal mucin deposition. Direct immunofluorescence is usually negative. The response to topical steroids or systemic antimalarial treatment is adequate. These patients have a recurrent but benign course. References 1 Costner MI, Sontheimer RD. Lupus erythematosus. In: Freedberg IM, Eisen AI, Wolff K, et al., eds. Fitzpatrick’s Dermatology in General Medicine, 6th edn. New York: McGraw-Hill, 2003: 1677–1693. 2 Gougerot H, Burnier M. Lupus erythematosus tumidus. Bull Soc Fr Derm Syph 1930: 12: 91. 3 Hoffman E. Isolierter lupus erythematosus tumidus der gesichtshaut. Derm Zeitschr 1909; 16: 159–160. 4 Ruiz H, Sanchez JL. Tumid lupus erythematosus. Am J Dermatopathol 1999; 21: 356–360. 5 Dekle CL, Mannes KD, Davis LS, et al. Lupus tumidus. J Am Acad Dermatol 1999; 41: 250–253. 6 Kuhn A, Richter-Hintz D, Oslislo C, et al. Lupus erythematosus tumidus. A neglected subset of cutaneous lupus erythematosus: report of 40 cases. Arch Dermatol 2000; 136: 1033–1041. 7 Sontheimer RD. Questions answered and a $1 million question raised concerning lupus erythematosus tumidus. Arch Dermatol 2000; 136: 1044–1049. 8 Kuhn A, Sonntag M, Sunderkötter C, et al. Upregulation of epidermal surface molecule expression in primary and ultraviolet-induced lesions of lupus erythematosus tumidus. Br J Dermatol 2002; 146: 801–809. 9 Kuhn A, Sonntag M, Ruzicka T, et al. Histopathologic
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findings in lupus erythematosus tumidus: review of 80 patients. J Am Acad Dermatol 2003; 48: 901– 908. Alexiadas-Amenakas MR, Baldassano M, Bince B, et al. Tumid lupus erythematosus: criteria for classification with immunohistochemical analysis. Arthr Rheum Care Res 2003; 119: 494–500. Kuhn A, Sonntag M, Richter-Hintz D, et al. Phototesting in lupus erythematosus tumidus – review of 60 patients. Photochem Photobiol 2001; 73: 532–536. Sanders CJ, Van Weelden H, Kazzaz GA, et al. Photosensitivity in patients with lupus erythematosus: a clinical and photobiological study of 100 patients using a prolonged photo test protocol. Br J Dermatol 2003; 149: 131–137. Norris DA. Pathomechanisms of photosensitive lupus erythematosus. J Invest Dermatol 1993; 100: 58s– 68s. Ackerman AB. Histologic Diagnosis of Inflammatory Skin Diseases. Baltimore: Williams & Williams, 1997: 529. Cardinali C, Caproni M, Bernacchi E, et al. The spectrum of cutaneous manifestations in lupus erythematosus – the Italian experience. Lupus 2000; 9: 417–423. Jolly M, Laumann AE, Shea CR, et al. Lupus erythematosus tumidus in systemic lupus erythematosus: novel association and possible role of early treatment in prevention of discoid lupus erythematosus. Lupus 2004; 13: 64–69. Weber F, Schmuth M, Fritsch P, et al. Lymphocytic infiltration of the skin is a photosensitive variant of lupus erythematosus: evidence by phototesting. Br J Dermatol 2002; 144: 292–296. Stratigos AJ, Antoniou C, Katsambas AD. Polymorphic light eruption. J Eur Acad Dermatol Venereol 2002; 16: 193–206. Lehmann P, Hölzle E, Kind P, et al. Experimental reproduction of skin lesions in lupus erythematosus by UVA and UVB radiation. J Am Acad Dermatol 1990; 22: 181–187. Del Pozo J, Peña C, Almagro M, et al. Systemic lupus erythematosus presenting with a reticular erythematous mucinosis-like condition. Lupus 2000; 9: 144–146.
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