Relapsing coalescent papular dermatosis of elderly patients: a precursor or an abortive lesion of Ofuji papuloerythroderma

ARTICLE

Auteur(s) : Kimio FUJII, Yuko KANNO, Kenji KONISHI, Noriko OHGOU

Department of Dermatology, Kobe City General Hospital, Minatojima Nakamachi 4-6, Chuo-Ku, Kobe, 650-0046 Japan

Article accepted on 15/01/2003

In 1984 Ofuji reported four cases of diffuse erythrodermatous skin lesions under the dermatological term of papuloerythroderma [1]. In his original report Ofuji stated that a solid papular lesion was the primary cutaneous manifestation of papuloerythroderma. He also referred to red papules appearing in groups in some parts of the body during the exacerbation of diffuse erythroderma. Subsequent to the initial report, more than 30 cases have been reported in English literature [2-14], all of which presented the typical, diffuse erythrodermatous lesion with a characteristic distribution pattern referred to as the deck-chair sign. In most of these cases coalescent flat-topped papules developed prior to or in association with the evolution of a typical, diffuse erythrodermatous lesion. The coalescent papules, therefore, are the precursor dermatological conditions for the diffuse erythroderma. It remains unknown if papular lesions develop only in association with diffuse erythrodermatous lesions or if there is an ‘abortive’ form of papular lesions that fails to evolve into diffuse erythroderma. We observed a group of elderly, predominantly male patients with a characteristic dermatological manifestation. It was an intensely pruritic, solid, flat-topped red papule developing in crops in a fairly defined area of the body. They often coalesced with each other into larger, polygonal flat-topped papules or plaques that were separated by a zone of normal skin. It followed a protracted course with repeated relapses without known precipitating factors. Histopathologically, both papular and coalescent lesions showed superficial perivascular dermatitis composed of lymphohistiocytic infiltrate admixed with varying numbers of eosinophils. In view of the clinicopathological features simulating those of the papular lesion that was originally described by Ofuji, we propose that these cases represent a precursor or an abortive state of Ofuji papuloerythroderma.

Patients and methods

All the 43 patients were seen at the outpatient clinic of the Department of Dermatology, Kobe City General Hospital, from 1997 to 2001, which corresponded to approximately 0.022% of the total new cases attending the department during the same period. The 43 patients ranged in age from 41 to 90 years with an average of 71.1 ± 12.1. Male patients dominated female patients by the ratio of 36:7. Patients suspected of drug-induced skin rash were excluded. Forty-three biopsy specimens were taken from papular (28 cases) or coalescent plaque (15 cases) lesions in 43 patients, and subjected to routine hematoxylin-eosin staining. Partial remission and relapse in this study were defined as more than 50% decrease or 50% increase, respectively, in the size of the area with active skin lesions.

Results

Dermatological manifestations

The skin rashes started as solitary, non-follicular, red or dark-reddish papules measuring a few mm in diameter (Figs. 1A and 1E). They were non-scaly, solid, monomorphic glossy papules, and usually developed in crops on a fairly defined area. They were so intensely pruritic that sleep was often disturbed. Histopathological findings of papular lesions were compact perivascular infiltration of mononuclear cells containing varying populations of eosinophils in the papillary and upper reticular dermis (Fig. 2A). Varying degrees of papillary and upper reticular edema were present. Approximately one-fourth of the biopsy specimens showed restricted areas of epidermal spongiosis and parakeratosis, but the epidermal change was never a dominant feature. The primary papular lesions, if they progressively worsened, coalesced into a polygonal or irregularly shaped, flat-topped, erythematous papular or plaque lesion (Figs. 1B and 1F) that expanded beyond the configuration of the cutaneous area. Desquamation was hardly observed on the coalescent plaque lesion. The proportion between papular and coalescent plaque components varied in individual lesions. When coalescent plaque lesions dominated, they were often separated from each other by a zone of normal skin so that they presented a cobble stone-like appearance (Fig. 1C). Histopathological findings of such coalescent lesions were essentially identical to those of the initial papular lesion except for slightly more acanthotic epidermis (Fig. 2B). The epidermis, however, never showed such marked acanthosis with elongation of rete ridges nor did the papillary dermis show deposit of thick collagen fibers as is seen in lichenified eczema or nodular prurigo. The skin rash healed with heavy pigmentation and little desquamation upon remission.
The skin rash showed characteristic predilection sites. At the beginning the lower back was affected in all cases without exception. When the disease was active, the skin rash might expand to involve the lateral thorax, buttocks, extensor surfaces of the limbs, lower abdomen, anterior chest, upper back, thighs, calf, lateral and posterior aspects of the neck as well. The flexor surfaces of the upper limb, scalp, palms and soles were only infrequently affected. When the scalp, palms or soles were involved, the skin rash showed diffuse scaly erythema. The axillae, groin, face, cubital and popliteal fossae, and large crease in the abdomen or thorax (Fig. 1D) were by no means involved even in advanced cases. In six of the 43 cases, coalescent plaque lesions spread to involve approximately two-thirds of the skin surface of the trunk, simulating papuloerythroderma (Fig. 1D). In the rest of the cases, normal skin remained intervening between papular or coalescent plaque lesions (Figs. 1E and 1F), and the skin rash never showed diffuse erythrodermatous patterns. The extension of the skin rash and the tendency of the initial papular lesion to coalesce varied from individual to individual and also varied in each episode of exacerbation even in the same individual.

Patient characteristics and clinical course

The duration of the skin rash before visiting our department ranged from 1 week to four years with the median duration of 20 weeks. Only one patient had a past history of atopic dermatitis, but he did not show concomitant active eczematous lesion suggestive of atopic dermatitis. None had cutaneous T-cell lymphoma. The disease took a protracted course with repeated relapses without apparent precipitating factors. Thirty-four patients were followed-up for longer than 10 weeks. All but one of these 34 patients showed relapses of papular lesions after achieving complete or partial remission. On average 2.4 bouts of relapse occurred during the mean follow-up period of 34.7 weeks.
Thirty-two patients were initially treated with potent topical steroids and oral antihistamines. The skin rash and pruritus were generally quite resistant to conventional treatment. One-third of the patients (11/32) achieved partial remission by the initial treatment, but none achieved complete remission. The remaining cases showed either no response or exacerbation. Thirty-six of the 43 cases were eventually treated with etretinate as in papuloerythroderma [13], resulting in complete (23 cases), partial (10 cases) remission, or no response (3 cases). Twenty-three of the 43 patients showed mild eosinophilia without evidence of concomitant allergic or parasitic diseases except for a case with bronchial asthma. The maximum eosinophil count was 4 000/μl (differential count: 40%), but mostly eosinophil counts were below 2 000/μl (the average: 800/μl). The eosinophil count changed in accordance with the disease activity, and returned within the normal range during remission. Serum IgE levels were determined in 30 cases and 14 of them showed moderately elevated serum IgE levels (the maximum: 3570 U/ml, the average: 685 U/ml, normal range: < 270 U/ml) without overt clinical evidence of allergic rhinitis or asthma. The level had no apparent correlation with eosinophil count or disease activity.

Discussion

The clinicopathological features common to the present 43 cases were: 1) intensely pruritic papular dermatosis with inherent tendency to coalesce, 2) recurrent and protracted clinical course with resistance to conventional topical treatment, 3) characteristic predilection site and predominance of elderly male patients, and 4) rather inconspicuous histopathological findings showing perivascular infiltration of mononuclear cells with varying populations of eosinophils. These clinicopathological features easily differentiate the disease from eczematous dermatosis including atopic dermatitis, nummular dermatitis, auto-sensitization dermatitis, lichen Vidal, or chronic contact dermatitis of unidentified contact allergens. We have tentatively included these cases as prurigo chronica multiformis [13, 16], which is a form of subacute prurigo with a neurodermatitis trait [15]. The coalescent nature of the disease and almost complete disappearance of papular/prurigous components in the course of coalescence, however, should distinguish the disease from any form of prurigous dermatosis.
It is clearly documented that some papuloerythroderma patients have preceding histories of pruritic papular lesions prior to developing diffuse erythroderma [1, 4, 5, 7-10, 12, 14]. Although some authors speculate that Ofuji papuloerythroderma is simply an unusual expression in an elderly population of a common form of dermatosis such as eczema and psoriasis [5], there is no evidence that any known dermatological disease evolves into Ofuji papuloerythroderma. Therefore, aside from the possible heterogeneity of etiology [17], the coalescent papular lesion constitutes a specific preceding dermatosis of papuloerythroderma of its own. The above-mentioned clinicopathological features common to the present 43 cases are compatible with those of the primary papular lesions that were originally described by Ofuji [1]. Moderate degrees of peripheral blood eosinophilia and elevated serum IgE levels in about half of the cases with no present histories of atopic diathesis are also consistent with the laboratory findings of papuloerythroderma. Above all, a proportion of cases (6/43) progressed to develop areas of diffuse erythrodermatous lesions on the trunk that were almost indistinguishable from papuloerythroderma (Fig. 1D). These observations suggest that Ofuji papuloerythroderma and the relapsing coalescent papular dermatosis of the present cases belong to the same disease spectrum and that our cases represent a preceding or an abortive phase of Ofuji papuloerythroderma.
We speculate that only a limited fraction of patients with a preceding skin lesion evolve into the diffuse erythrodermatous condition that qualifies to be diagnosed as papuloerythroderma. Probably a larger proportion of patients has repeated relapses of coalescent papular lesions in a restricted area of the body that never evolve into diffuse erythroderma, thus remaining un- or mis-diagnosed. A careful and long-term clinicopathological follow-up of a patient with typical Ofuji papuloerythroderma would further verify the presence of an abortive state of the rare dermatosis. n

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