Subcorneal pustular dermatosis and IGA myeloma : a uncommon association but probably not coincidental

ARTICLE

Subcorneal pustular dermatosis (SCPD) is a rare chronic neutrophilic dermatosis, sometimes associated with benign or malignant IgA paraproteinemia, usually seen in middle-aged females [1-3]. It appears as superficial pustules, that may coalesce to form circinate or polycyclic patterns, mainly located on the trunk and in intertriginous areas. Histologically it is characterised by a subcorneal accumulation of neutrophilic polymorphonuclear leukocytes and a mild perivascular infiltration of lymphocytes in the upper dermis; although in some cases immunofluorescence staining has been observed, there are no characteristic immunopathological changes.

The disease responds to dapsone therapy but etretinate, alone or in combination with dapsone, is reported to have benefical effects [2, 14].

This report presents a case of SCPD associated with IgAlambda myeloma and reviews the literature for similar cases.

Case report

The patient was a 71-year old white man who had at least a 30-year history of a relapsing pruritic pustular eruption mainly affecting the trunk and intertriginous areas explained as pustular psoriasis only on the basis of clinical data. The disease persisted for years, without compromising the general state of health, until six months ago, when symptoms of deep fatigue, stress dyspnea, diffuse chest pain and fever arose.

When the patient reached our observation annular and polycyclic lesions with erythematous crusting and slightly prominent edges were noted. The area of these lesions was studded with grouped and isolated pustules (2-8 mm in diameter) while the centres were covered by leafy scales (Fig. 1a); as they healed a mild hyperpigmentation remained. The lesions were localized all over the body, especially prominent in the anterior trunk, back, periumbilical region and lower abdomen, axillae, groins and the flexor areas of the upper and lower limbs. The mucous membranes, face, scalp, palms and soles were unaffected. The appearance and extension of the lesions, during the relapses of the pustules, were accompained by itching.

The results of laboratory tests were as follows: white blood cell count 6,100/mm³ (65% neutrophils, 33% lymphocytes, 1% monocytes, 1% eosinophils); hemoglobin 10.0 g/dl; platelets 203,000/ mm³; erythrocyte sedimentation rate 100 mm in the first hour; serum immunoelectrophoresis revealed a monoclonal gammopathy characterized by depressed IgG and IgM levels (373 mg/ml and 6 mg/ml respectively), with a markedly elevated IgA level (2,092 mg/ml) in association with a lambda light chain; urine protein electrophoresis confirmed the presence of Bence-Jones' protein (1.80 g/l) and plasmatic ß2-microglobulin increased in quantity (6.1 mg/l).

Skeletal x-rays showed normal bone density without lytic lesion or any other abnormality.

The bone marrow aspirate showed a moderate hypoplasia of the maturative cell lines and the infiltration of plasmoblasts, which were about the 50% of the cell population.

A culture performed from cutaneous pustules showed neither bacterial nor fungal growth.

The histological examination of the lesional skin revealed a subcorneal pustule with numerous polymorphonuclear leukocytes: acanthosis in correspondence to the pustule and abundant neutrophils migrating through the epidermal cells. Perivascular infiltration of neutrophils and lymphocytes in the papillary dermis was observed (Fig. 2). Direct immunofluorescence of the affected skin was negative for IgG, IgM, IgA, C3 and C1q.

A diagnosis of subcorneal pustular dermatosis (SCPD) and II stage IgAlambda myeloma was made on the basis of the clinical picture together with the histopathological findings and laboratory results.

The patient was treated according to the MIP protocol (melphalan 15 mg, Idarubicina 10 mg, Prednisone 125 mg) for 4 days for a total of six therapeutic cycles/month, which resulted in a 50% reduction of the monoclonal component.

Unfortunately this treatment had no effect on the skin lesions. The patient was then treated with etretinate, 1 mg/kg/day for 5 days, followed by 0,75 mg/kg/day for 8 weeks with a good improvement of the cutaneous picture (Fig. 1b).

The patient made an uneventful haematological recovery and is now healthy after 10 months follow-up.

Discussion

Described by Sneddon and Wilkinson in 1956 [1], SCPD, is an uncommon chronic neutrophilic dermatosis, characterized by relapsing pruritic pustular eruption usually affecting women after the fourth decade of life and often associated with benign monoclonal gammopathies and myelomas [2-3]. A new disease entity, clinically similar to SCPD but characterized by an intercellular IgA deposit in the epidermis [4-6], has been also recognized in the field of neutrophilic dermatosis. The "intercellular IgA vesiculo-pustular dermatosis" (IAVPD), according to Nishkawa et al. [7], can be divided into two sub-types: the intraepidermal neutrophilic type (characterized by intraepidermal bullae containing neutrophils and pemphigus-like IgA deposits in the entire epidermis) and the subcorneal pustular dermatosis type (characterized by subcorneal pustule formation with or without acantholysis and intercellular IgA deposits in the upper portion of the epidermis) [4-7].

The clinical, histopathological and immunopathological features of the present case are consistent with those of SCPD and not with those of SCPD-type IAVPD (absence of the intercellular IgA deposits).

Particularly interesting in this case is the association between the dermatosis and an IgAlambda myeloma described only three times before as far as we know and the longest period (30 years) of time between the onset of the dermatosis and that of the myelopathy observed up to now [3].

The significance of this association is not yet known, but it is certainly not a coincidence. In fact, an increasing number of reports show the association between myeloproliferative disorders and neutrophilic dermatosis, such as SCPD [2-3], pyoderma gangrenosum [8] and Sweet's syndrome [9] either isolated or in association with them; furthermore SCPD [10], pyoderma gangrenosum [11], Sweet's syndrome [12] and other neutrophilic dermatoses [10] were reported to develop in patients who underwent treatment with granulocyte colony-stimulating factor and granulocyte-macrophage colony-stimulating factor which enhances the neutrophil function and chemotaxis [13].

On this basis it is possible to hypothesize the existence of a common pathophysiology for this spectrum of diseases characterized by a "pathogenic link between IgA dysfunction and neutrophilic disorders" [6]. Furthermore the possibility that chronic antigenic stimuli not yet perfectly clear, could stimulate the production of monoclonal immunoglobulins, can not be excluded (the cutaneous lesions preceded the occurrence of myeloma by several years) [2]. This topic is worth further investigation. In conclusion, this case suggests the importance of performing regular immunoelectrophoretic evaluation of patients affected with SCPD, or other neutrophilic dermatosis, and the good therapeutic response of cutaneous lesions to etretinate (which is able to inhibit the function and migration of neutrophils) [2, 14], useful in the management of severe recalcitrant forms of SCPD.

REFERENCES

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