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Subcorneal pustulosis and Pyoderma gangrenosum associated with a biclonal gammopathy

European Journal of Dermatology. Volume 16, Number 6, 687-90, November-December 2006, Clinical report

DOI : 10.1684/ejd.2006.0010

Summary

Author(s) : I Puechguiral-Renaud, O Carpentier, F Piette, E Delaporte , Clinique dermatologique, Hôpital Claude Huriez, Centre Hospitalier Universitaire, 1, rue Michel Polonowski, 59037 Lille Cedex, France.

Summary : Pyoderma gangrenosum and subcorneal pustulosis are two neutrophilic dermatoses. Their occurrence in the same patient is rare and may be related to an IgA dysglobulinemia. We report a case presenting these two conditions associated with a biclonal benign IgA and IgG gammopathy. A 67-year-old man exhibited typical pyoderma gangrenosum associated after three years duration with subcorneal pustulosis lesions, confirmed by cutaneous biopsy.Laboratory results showed a biclonal benign IgA and IgG kappa gammopathy. Therapeutic management was difficult: Pyoderma gangrenosum responded well to corticosteroids but subcorneal pustulosis management was harder and treatments were poorly effective.Pyoderma gangrenosum and subcorneal pustulosis are a part of the neutrophilic spectrum. Their association has been only reported in eleven patients. In eight cases, an IgA dysglobulinemia was associated suggesting its responsibility in the occurrence of both dermatoses. Treatments are various and not fully effective. If the Pyoderma gangrenosum usually responds to corticosteroids, the subcorneal pustulosis treatments are not well defined and often not efficient. Our case illustrates the dissociated evolution of these two dermatoses and their difficult global management. During the follow-up, a regular search for dysglobulinemia is required in order to detect malignant transformations.

Keywords : Biclonal gammopathy, Neutrophilic dermatosis, Pyoderma gangrenosum, subcorneal pustular dermatosis

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ARTICLE

Auteur(s) : I Puechguiral-Renaud, O Carpentier, F Piette, E Delaporte

Clinique dermatologique, Hôpital Claude Huriez, Centre Hospitalier Universitaire, 1, rue Michel Polonowski, 59037 Lille Cedex, France

accepté le 3 Juillet 2006

Pyoderma gangrenosum (PG) and subcorneal pustular dermatosis (SCPD) are two neutrophilic dermatoses. Their occurrence in the same patient is rare and seems to be strongly correlated with an IgA dysglobulinemia. We report the case of a patient with both PG and SCPD in association with a biclonal IgA and IgG benign gammopathy.

Case report

In 1998, a 67 year-old-man, an active smoker, presented for the first time with large ulcers on his lower body and chest area. A PG was diagnosed. Laboratory results showed a monoclonal benign IgA Kappa gammopathy. The patient was successfully treated with colchicine 1mg daily. In July 2001, new PG episodes occurred on the legs and the lumbar area. The ulcers were associated with ill defined plaques with pustules at different stages of development, scales and crusts and an association with a SCPD was suspected. No histological examination was performed at that time. Colchicine was replaced by dapsone (100 mg daily) which gave less satisfactory results. Then, colchicine was reintroduced (1 mg daily) in combination with dapsone (100 mg daily) but the lesions gradually spread, leading to hospital admission in June 2003. Active PG ulcerations involving the lumbo-sacral area and the right side and posterior face of the upper left arm appeared fibrino-necrotic and were painful and malodorous ( (figure 1) ). Pigmented scars of old PG ulcerations on the legs were also noted. At the same time the patient showed polycyclic erythematous and crusty lesions with a pustulous border on the legs, trunk, axillae and groin areas. These were diagnosed as an SCPD eruption ( (figure 2) ). Mucous membranes were not involved. A finger clubbing and a chesty cough were noted.

Skin biopsies of left inguinal and right axillary folds revealed subcorneal pustules filled with many neutrophils ( (figure 3) ). There was no acantholysis. A moderate perivascular inflammatory infiltration was present in the upper dermis. Direct immunofluorescence was negative. This histological data led to the diagnosis of SCPD. Biopsy of PG was not performed because of the pathergy risk. Peripheral blood cell counts showed elevated neutrophils (10000/mm³), erythrocyte sedimentation rate mildly elevated at 35 mm/h but C reactive protein was normal. Serum immunoelectrophoresis identified a biclonal IgA kappa and IgG kappa protein. Results of urine testing for Bence-Jones protein and immunoelectrophoresis were negative. Ears, nose and throat examination and laryngoscopy were normal. Bone marrow aspirate, radiological skeletal survey, bronchial and gastric fibroscopy, colonoscopy and computerized axial tomography were normal. Combined therapy with prednisolone 1 mg/kg/d and colchicine 1 mg daily was started. The purulent ulcerations healed with scarring within three months; prednisone later was tapered to 20 mg a day. On the other hand, SCPD slowly extended and became pruriginous. Addition of Psoralen- Ultraviolet A therapy was started with partial response and transient control of SCPD. As corticosteroid treatment was gradually tapered off, PG slightly relapsed and SCPD became more pruritic. The patient was then given intramuscular injections of methorexate with gradually increasing doses (until 17.5 mg per week) in association with prednisone 8 mg daily. At present time, PG is totally healed but SCPD is only partially controlled.

Discussion

PG and SCPD belong to the neutrophilic “spectrum” [1]. Their clinicopathological characteristics are well defined and quite distinct but they share common features such as their association with systemic diseases. Gammopathies (paraproteinemias) or myeloproliferative disorders represent a significant part of these associations.

SCPD is a rare, chronic, relapsing disease. About two hundred cases have been reported, the majority in association with a monoclonal gammopathy [2, 3]. This paraproteinemia is mainly of benign IgA type for about 80% of the reports; other cases are IgG types. A few cases describe an IgA myeloma [4, 5]. Other associations with systemic diseases including inflammatory bowel diseases, neoplasia or joint immunological disorders are rarer than in other neutrophilic dermatoses [6-9]. Dapsone is usually the most effective treatment for SCPD [10]. Some cases may be refractory and other treatments used in single therapy or in combination are proposed: colchicine, salazosulfapyridine, acitretin, PUVA and recently methotrexate or infliximab [11-17].

Fifty to 70% of PG are associated with systemic diseases. PG is described with monoclonal gammopathy of undetermined significance in numerous cases [18, 19] more rarely with other haematological diseases such as IgA myeloma or leukemia [20, 21].

Only a few reports in literature describe SCPD in association with PG [1, 22-31]. All cases are summarized in table 1( Table 1 ). Our case is the twelfth to our knowledge. All patients but three [1, 23, 25] also presented an associated benign monoclonal IgA paraproteinemia or an IgA myeloma [22]. Our case is the first to report a benign biclonal IgA and IgG gammopathy with both PG and SCPD. The prevalence of mono- and biclonal gammopathies in the general population ranges between 1-3% and only 1% is biclonal. Our case suggests recommending an annual gammopathy research in patients with these two neutrophilic dermatoses and a close follow-up because the risk of progression to a malignant plasma-cell disorder is 1% per year [32]. Although there is an apparent link between IgA and these two neutrophilic diseases, physiopathology remains unclear. The immunological mechanisms implicated are not yet defined. IgA auto-antibodies could interact directly with specific receptors on neutrophils, activating them. They could also interact in the skin with unknown target antigens which may lead to the production of specific neutrophils chemokines.

Corticosteroid treatment in monotherapy or in combination with dapsone is the most frequently used in cases associating SCPD with PG. As opposed to what we observed, these treatments in the literature mostly lead to a complete resolution of both lesions. However, because of the frequent relapses for PG and SCPD other second-choice therapies are proposed with variable results.
Table 1 Literature reports about Pyoderma Gangrenosum (PG) associated with Subcorneal pustular dermatosis (SCPD)

Cases	Age /Sex	Clinical features	Associated diseases	Treatments	Course
Our case	67/M	PG 3 years before SCPD	Biclonal IgA and IgG gammopathy	1. Prednisolone/colchicine	1. Only PG controlled
2. Predisolone/PUVA	2. Control of both diseases with relapses
3. Prednisolone/methotrexate	3. PG controlled and SCPD less responsive
Wolff K. (1971) [29]	47/F	SCPD 6 years before PG	IgA monoclonal gammopathy	1. Dapsone	1. SCPD controlled with relapses
2. Sulfapyridine	2. Partial control of both diseases with relapses
Venning VA et al. (1986) [30]	59/M	SCPD 6 years before PG	IgA monoclonal gammopathy	Dapsone/topical corticoids	Control of both diseases
Marsden JR et al. (1986) [24]	52/M	SCPD 2 months before PG	IgA monoclonal gammopathy	1. Dapsone	1. Only SCPD controlled
2. Dapsone/prednisolone	2. Control of both diseases
Dallot A et al. (1988) [26]	39/F	SCPD 6 years before PG	IgA monoclonal gammopathy	1. Dapsone	1. SCPD controlled with relapses
Amicrobial lymph node suppuration
Aseptic spleen abscesses	2. Prednisolone	2. Control of both diseases
Freire Murgueytio P et al. (1989) [25]	64/F	Concomitant SCPD and PG	IgA monoclonal gammopathy	Prednisolone/minocycline	Partial control of both diseases with relapses
Seronegative arthritis
Normocytic anaemia
Sural thrombophlebitis
Vignon-Pennamen MD et al. (1991) [1]	66/F	Concomitant SCPD and PG	No paraproteinemia	Prednisolone/topical corticoids	Control of both diseases
Refractory anaemia with blast excess
Mixed connective tissue disease
Kohl PK et al. (1991) [31]	60/F	PG 6 months before SCPD	IgA monoclonal gammopathy	1. Prednisolone/minocycline	1. PG not controlled
Latent syphilis
Hypertension	2. Sulfapyridine	2. PG controlled
Diabetes mellitus type II	3. Dapsone	3. SCPD partially controlled with relapses
Scerri L et al. (1994) [23]	89/F	PG 2 years before SCPD	No paraproteinemia	1. Prednisolone	1. PG partially controlled with relapses
Pernicious anaemia
Autoimmune hypothyroidism	2. Prednisolone/dapsone	2. Control of both diseases
Cartier H et al. (1995) [28]	67/F	PG 1 year before SCPD	IgA monoclonal gammopathy	1. Prednisolone	1. PG partially controlled with relapses
Asymptomatic rheumatoid arthritis
Neutrophilic pulmonary involvement	2. Prednisolone/dapsone	2. Control of both diseases
Stone MS et al. (1996) [22]	72/F	SCPD 9 years before PG	IgA myeloma	Dapsone/prednisolone	PG controlled and SCPD less responsive
Chave TA et al. (2001) [27]	82/M	SCPD 5 months before PG	IgA monoclonal gammopathy	Prednisolone	SCPD controlled and PG less responsive
Hypertension
Diabetes mellitus type II

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