Pemphigus vegetans presenting as acrodermatitis continua suppurativa

ARTICLE

Auteur(s) : László TÖRÖK¹, Sándor HUSZ², Henriette ÓCSAI¹, Ágnes KRISCHNER¹, Mária KISS²

¹Department of Dermatology, County Hospital, Nagykörösi u 15, 6000 Kecskemét, Hungary
²Department of Dermatology and Allergology, Medical Faculty of Szeged University, Szeged, Hungary

Article accepted on 31/7/03

Case report

Four months ago a 51-year-old female observed pustulous vesicles on the distal phalanxes. Later the expanding pustulous lesions covered the feet. Due to a marked inflammatory edema and pain the patient became abasic. Loss of appetite, nausea, vomiting, diarrhoea, and loss of body weight aggravated the above symptoms.
Status at admission: nail loss on the 1^st, 3^rd and 4^th phalanxes of the right foot. Confluent pustulous eruptions covering the inflammed, edematous skin of the toes, feet, and the soles were observed. The pustulous lesions of the feet ran as trench-like, parallel lines (Fig. 1,  2). Confluent yellowish pustules with signs of paronychia covered the distal part of the 3^rd finger of the right hand. The navel and the inguinal fossa were covered with eroded skin with purulent exsudation. Rhagades with thick crusts developed at the angles of the mouth. The tongue was furred, and the edematous, loosened buccal mucosa exhibited signs of multiple erosion.
Laboratory findings: sedimentation 47-67 mm/h; eosinophilia (350-700mm³); X-ray of the toes and fingers revealed streaky calcium loss; bone scintigraphy showed pathological enrichment in the interphalangeal and metatarso-phalangeal joints. HLA (performed at the Transfusion Center of the University of Szeged): A1,2,3, B1, 17/58, B2, 37, CW1, 3, CW2, CW6 (A1, B37, and CW6 positivity indicated susceptibility to psoriasis).
The first histological findings showed spongiosiform pustules with neutrophilic cell infiltration under hyperkeratotic epithelium. Marked dermal inflammatory cell infiltration mainly consisted of neutrophil granulocytes; the eosinophil count was also elevated. Histological findings suggested acrodermatitis continua suppurativa, however, the increased count of eosinophil granulocytes and the lack of typical psoriasiform lesions of the epithelium did not match the histological picture of the assumed diagnosis. As the patient was resistant to acitretin and local PUVA-acitretin combined therapy, two further biopsies were taken.
The second histological examination revealed cleavage formation with acantholytic cells; the vesicles contained red blood cells and neutrophil granulocytes. Results of the third histological study showed hyperkeratotic epithelial cells with signs of necrobiosis, and necrobiotic tissue remnants that contained pus cells, and to a lesser extent, eosinophil cells. These findings suggested dermatosis with acantholysis, so a 4^th punch biopsy for repeated immunohistology was taken from one of the foot vesicles with turbid content.
Direct immunofluorescent study with IgG and C3 exhibited intercellular reaction. In healthy human skin indirect immunofluorescent analysis revealed only minor intercellular reaction whereas the oesophagus of the monkey exhibits IgG positive fluorescence. The salt split technique failed to reveal any fluorescence. Western-blot analysis showed staining charasteristic of pemphigus vulgaris (130-kDa, desmoglein III), which further supports the diagnosis of pemphigus.
Therapy was initiated with low-dose steroids combined with azathioprin. Since rapid improvement was accompanied with myopathy, the steroid dose was lowered. By that time the patient complained of therapy-resistant nausea and vomiting, which could not be explained by any organic disease. Discontinuation of azathioprin stopped the nausea but led to an outbreak of the pustular symptoms. The low-dose steroid therapy was combined with a daily 300 mg cyclosporin-A. This combination induced full remission in 3 weeks. After a one-year long follow-up period the patient was symptom-free and still receives 75 mg cyclosporin-A and 8 mg methylprednisolone.

Discussion

Pemphigus vegetans, first described by Hallopeau in Paris at the 1^st International Congress on Dermatology and Syphilography in 1889, is a rare dermatosis. It is noteworthy that Hallopeau differentiated pemphigus vegetans with early pustulous signs described in his paper from the pemphigus vegetans first mentioned by Neuman in 1876. The latter is characterized by vesiculous and bullous primary lesions [1]. Later investigations and immunohistological findings supported Hallopeau's observations, and at present two clinical forms of pemphigus vegetans are identified. Similar to pemphigus vulgaris, bullous lesions are characteristic of the onset and end of the Neuman type of the disease. The bullous lesions, as well as postbullous erosions are prone to papillomatous vegetation, especially in the flexures. In the Hallopeau (pustulous) form, vesicles and bullae are not typical, since pustulous lesions with subsequent vegetation are the basic symptoms of the disease [2].
Both forms of vegetating pemphigus have a similar immunohistological profile and, probably, similar prognosis. Recent findings describe target antigens that occur in pemphigus vulgaris, while there is scarcely any data on the antigens typical of pemphigus vegetans (most probably desmoglein 3, desmocollin 1-3) [3]. Moreover, it is not yet clear whether the antibodies occurring in pemphigus vulgaris and pemphigus vegetans show any differences. IgG₁ and IgG₄ autoantibodies are typical of pemphigus vulgaris, whereas presence of IgG₂ and IgG₄ isotypes were demonstrated in the lesional skin of pemphigus vegetans (Hallopeau form). There is scarcely any information on the pathogenesis of pemphigus vegetans. Most probably different tissue factors, i.e. cytokines play an important part in the development of epidermal proliferation and chemotaxis of eosinophils [4].
The nail apparatus is rarely involved in pemphigus vulgaris. As a rule onycholysis, onychomadesis, paronychia, hemorrhages and erosions of the nail matrix, and nail atrophy are the leading symptoms of pemphigus vulgaris [5-8]. Data from the literature show that the nail symptoms are partial manifestations of the skin and mucosal involvement typical of pemphigus. Only very rarely do nail symptoms develop several months prior to manifestation of pemphigus vulgaris [9]. In such cases diagnosis should be based on immunohistological findings.
There is a single publication which describes phalangeal and nail involvement in Hallopeau's pemphigus vegetans. In 1982 Leroy et al. presented a case of Hallopeau's pemphigus vegetans with extended skin and mucosal symptoms and the involvement of the left 3^rd finger (1). At compression a sterile, purulent fluid was discharged from the fluctuating pustulous periungual lesions. Later onycholysis developed on all phalanxes.
It is of special interest that Hallopeau's pemphigus vegetans manifested as an acrodermatitis continua suppurativa first affected the nail area and the fingers, and only months later early symptoms of pemphigus vegetans developed in the flexures and the buccal mucosa. (Presence of certain psoriatic HLA loci might explain manifestation similar to the pustulous psoriasis). Heterogeneity of histological findings was caused by degenerative histological changes and development of vegetating pustulous foci. Due to the occurrence of pustulous foci and degenerative histological alterations, repeated biopsies were taken and they showed a heterogenous picture that only partially corresponded to acrodermatitis continua suppurativa. There were only a few sites where the intraepithelial cleavage formation suggested pemphigus. Histological findings showed a marked increase in eosinophil count typical of pemphigus vegetans. The response and long-term remission induced by cyclosporine-A and low-dose steroid therapy was noteworthy. The literature also mentions acitretin and steroids as an alternative therapeutic tool in pemphigus vegetans [10, 11].
The symptoms of the pustulous alterations of the fingers in Hallopeau's pemphigus vegetans should be differentiated from acrodermatitis continua suppurativa (Kogoj's spongiosiform pustules), and from blenorrheal keratoderma of Reiter's disease. In progressive cases, when the buccal mucosa and the flexures are involved, the disease should also be differentiated from the vegetant pyodermatitis-pyostomatitis [12]. Differential diagnosis is mainly based on immunohistological findings that are negative in vegetant pyodermatitis-pyostomatitis, but show a clearly visible direct and indirect immunofluorescence in pemphigus vegetans. Furthermore, these diseases have different outcomes: while the prognosis of pemphigus vegetans without immunosuppressive therapy is poor, that of the vegetant pyodermatitis-pyostomatitis is more favorable. Even in cases associated with inflammatory intestinal processes, a rapid remission is induced by a short-term steroid therapy [13].
In summary: a rare type of Hallopeau's pemphigus vegetans with a special localization is presented. First manifestation of the symptoms on the toes can be misleading and should be differentiated from acrodermatitis continua suppurativa. The authors emphasize the importance of immunohistological studies which can play a key diagnostic role in cases of therapy-resistant, progressive, exuberant acropustulosis. n

References

1. Leroy D, Lebrun J, Maillard V, Mandard J-C, Deschamps P. Pemphigus végétant a type clinique de dermatite pustuleuse chronique de Hallopeau. Ann Dermatol Venereol 1982; 109: 549-55.

2. Jansen T, Messer G, Meurer M, Plewig G. Pemphigus vegetans. Hautarzt 2001; 52: 504-9.

3. Hashimoto K, Hashimoto T, Higashiyama M, Nishikawa T, Garrod DR, Yoshikawa K. Detection of antidesmocollins I and II antibodies in two cases of Hallopeau type pemhigus vegetans by immunoblot analysis. J Dermatol Sci 1994; 7: 100-6.

4. Hashizume H, Iwatsuki K, Takigawa M. Epidermal antigens and complement-binding anti-intercellular antibodies in pemphigus vegetans, Hallopeau type. Brit J Dermatol 1993; 129: 739-43.

5. Engineer L, Norton LA, Ahmed AR. Nail involvement in pemphigus vulgaris. J Am Acad Dermatol 2000; 43: 529-35.

6. Fulton RA, Campbell I, Carlyle D, Simpson NB. Nail Bed Immunfluorescence in Pemphigus vulgaris. Acta Dermatovener 1983; 63: 170-2.

7. Kim BS, Song KY, Chung JH. Paronychia — a manifestation of pemphigus vulgaris. Clin Exp Dermatol 1996; 21: 315-7.

8. Schlesinger N, Katz M, Ingber A. Nail involvement in pemphigus vulgaris journal missing 2002; 5: 836-9.

9. Akiyama C. Paronychia: a sign heralding an exacerbation of pemphigus vulgaris. J Am Acad Dermatol 1993; 29: 494-6.

10. Huilgol SC, Black MM. Management of the immunobullous disorders. II. Pemphigus. Clin Exp Dermatol 1995; 20: 283-93.

11. Ichimiya M, Yamamoto K, Muto M. Successful treatment of pemphigus vegetans by addition of etretinate to systemic steroids. Clin Exp Dermatol 1998; 23: 178-80.

12. Mehravaran M, Kemény L, Husz S, Korom I, Kiss M, Dobozí A. Pyodermatitis-pyostomatitis vegetans. Brit J Dermatol 1997; 137: 266-9.

13. Delaporte E, Viget N, Pasturel-Michon U, Catteau B, Hachulla E, Piete F. Pyostomatitis-pyodermatitis vegetans revealing Crohn disease. Ann Dermatol Venereol 1998; 125: 331-4.