Sub Corneal Pustular

 

Dermatosis  Sneddon

 

Wilkinson Disease

 

Sub-corneal pustular dermatosis (SPD) is a rare, chronic, recurrent, pustular eruption characterized histopathologically by sub-corneal pustules that contain abundant neutrophils. The condition was originally described in 1956 by Sneddon and Wilkinson, who separated SPD from other previously unclassified pustular eruptions. Until 1966, when the first comprehensive review appeared, more than 130 cases had been reported, but not all fulfilled the clinical and histopathologic criteria required for this diagnosis.A considerable number of additional cases have since appeared in the literature, and a sub-type with intraepidermal deposits of immunoglobulin A (IgA) directed against desmocollin 1 has been recognized.³ Today, these cases are usually classified as SPD-type IgA pemphigus and it is a matter of debate whether the finding of epidermal IgA deposits define a subset of SPD or a new pemphigus variant that is otherwise indistinguishable from “classic” SPD.

 

▪ EPIDEMIOLOGY

There is no racial predilection. Most of the reported cases have been in whites, but the disease has also been observed in Africans, Japanese, and Chinese. The condition is more common in women and in persons older than 40 years of age, but SPD may occur at any age. A pustular eruption that is clinically and histologically similar to the human disease, which also responds to dapsone treatment, has been observed in dogs.

 

▪ ETIOLOGY AND PATHOGENESIS

The cause of SPD is unknown. Cultures of the pustules consistently do not reveal bacterial growth. The role of trigger mechanisms such as preceding or concomitant infections, though repeatedly discussed, has remained speculative. Immunologic mechanisms have been implicated in the pathogenesis, and in a subset of patients, whose disease clinically resembled SPD, intraepidermal IgA deposits have been detected. Some of these patients also had circulating IgA antibodies against the same sites within the epidermis. Desmocollin 1 has been described as an autoantigen in these cases and the disease has been classified as a rare pemphigus variant (SPD-type IgA pemphigus). The pathogenetic role of these antibodies is still to be demonstrated.

The occasional association of SPD with certain other diseases may represent more than a mere coincidence. Increased serum IgA has been detected in a number of patients, and the disease has been reported to occur in cases of IgA-paraproteinemia and IgA multiple myeloma. In addition, SPD is associated with pyoderma gangrenosum, ulcerative colitis, and Crohn disease. On the other hand, pyoderma gangrenosum is not uncommon in patients with inflammatory bowel disease, paraproteinemia, and myeloma . Whether or not the co-existence of these conditions reflects common pathogenetic mechanisms remains to be clarified, but an additional common denominator linking these disorders is their response to sulfone and sulfonamide therapy.

Further associations reported to date include IgG paraproteinemia, CD30⁺ anaplastic large-cell lymphoma,

nonsmall cell lung cancer, apudoma, rheumatoid arthritis, hyperthyroidism, and mycoplasma pneumoniae infection.

 

▪ CLINICAL FINDINGS

The primary lesions are small, discrete, flaccid pustules or vesicles that rapidly turn pustular and usually arise in crops within a few hours on clinically normal or slightly erythematous skin . In dependent regions, pus characteristically accumulates in the lower half of the pustule ; as the pustules usually have the tendency to coalesce, they often, but not always, form annular, circinate, or bizarre serpiginous patterns. After a few days, the pustules rupture and dry up to form thin, superficial scales and crusts, closely resembling impetigo. Peripheral spreading and central healing leave polycyclic, erythematous areas in which new pustules arise as others disappear . There is no atrophy or scarring, but an occasional brownish hyperpigmentation may mark previously affected sites. Variable intervals of quiescence, lasting from a few days to several weeks, may be followed by the sudden development of new lesions. The eruptions tend to occur symmetrically, affecting mainly the axillae, groin, abdomen, submammary areas, and the flexor aspects of the limbs. In rare cases, the face, palms, and soles may be involved. Scalp and mucous membranes invariably remain free of lesions. Episodic itching and burning represent subjective symptoms in a small number of patients, but there are no systemic symptoms or abnormalities in routine laboratory parameters.

 

SUB-CORNEAL PUSTULAR DERMATOSIS AT A GLANCE

·         A rare condition with worldwide occurrence.

·         A chronic recurrent disorder with a benign course, frequently associated with various forms of immune dysfunction [most commonly immunoglobulin A (IgA) monoclonal gammopathy]. Occurrence of intraepidermal deposits of IgA indicate a relationship with IgA pemphigus.

·         Crops of flaccid, coalescing pustules; often in annular or serpiginous patterns.

·         Usually distributed symmetrically in the axillae, groins, submammary, the flexor aspects of the limbs, and on the abdomen.

·         Pathology: Sub-corneal pustules filled with polymorphonuclear leukocytes.

 

▪ HISTOPATHOLOGY

The hallmark of the disease is a strictly sub-corneal pustule filled with polymorphonuclear leukocytes,¹ with only an occasional eosinophil.² Acantholysis is not involved in pustule formation, but a few acantholytic cells may be found in older lesions (secondary acantholysis). Surprisingly, the epidermal layers underlying the pustule exhibit little pathology, and, apart from a variable number of migrating leukocytes, there is little evidence of spongiosis or cytolytic damage to the epidermal cells. The dermis contains a perivascular infiltrate composed

of neutrophils and rarely mononuclear cells and eosinophils .

In a subset of patients, direct immunofluorescence reveals intraepidermal IgA deposits. In these cases, IgA is usually present in a pemphigus-like intercellular pattern, either in the entire epidermis or confined to its upper layers. By indirect immunofluorescence, circulating IgA antibodies directed against the intercellular substance of the epidermis were detected in single cases. Today these cases are usually diagnosed as SPD-type IgA pemphigus .

Ultrastructural examination of paralesional skin has shown cytolysis of keratinocytes confined to the granular layer; the formation of pustules has been regarded as a secondary event caused by invasion and sub-corneal accumulation of leukocytes.

 

▪ DIFFERENTIAL DIAGNOSIS

An early localized eruption of SPD may be clinically and histologically indistinguishable from impetigo, but the distribution pattern of the lesions, the absence of bacteria in the pustules, the ineffectiveness of topical and systemic antibiotic therapy suggest the correct diagnosis. Dermatitis herpetiformis is also highly pruritic, affecting primarily the extensor surfaces and is sub-epidermal with IgA.

Pemphigus foliaceus has acantholysis and atypical immunofluorescence pattern. Generalized pustular psoriasis (von Zumbusch's type) presents with systemic symptoms (fever, malaise, leukocytosis), and spongiform pustules within the epidermis. The necrolytic migratory eruption of glucagonoma syndrome can be differentiated by its distribution, lack of actual pustule formation, erosions of the lips and oral mucosa, and, histologically, necrobiosis of the upper epidermis. Biochemically, excess levels of glucagon are diagnostic. Acute generalized pustulosis is widespread with predilection of the distal parts of the extremities, and histologically may exhibit leukocytoclastic vasculitis.

 

Differential Diagnosis of Sub-Corneal Pustular Dermatosis

·         Bacterial impetigo

·         Dermatitis herpetiformis

·         Pemphigus foliaceus

·         Immunoglobulin A pemphigus/intraepidermal immunoglobulin A pustulosis

·         Pustular psoriasis

·         Necrolytic migratory erythema

·         Acute generalized exanthematous pustulosis

 

▪ PROGNOSIS AND CLINICAL COURSE

SPD is a benign condition. Without treatment, attacks recur over many years and remissions are variable, lasting from a few days to several weeks. Despite the protracted course the general health of the patient is usually not impaired. However, one of our own cases who had SPD, pyoderma gangrenosum, and IgA paraproteinemia of more than 20 years' duration died of septicemia with staphylococcal abscesses in the lungs, liver, and spleen.

 

 

▪ TREATMENT

The drugs of choice are the sulfones , such as dapsone in a dose of 50 to 150 mg daily. The response is slower and less dramatic than in dermatitis herpetiformis, but complete remission is most often obtained. In some patients, the treatment may be withdrawn after several months, although in others it may have to be continued for years; the minimal effective dose to suppress disease should be determined in these patients. Sulfapyridine (1.0 to 3.0 g daily) is also beneficial; systemic corticosteroids are less effective, although they can suppress generalized flares when given in high doses. Retinoids, phototherapy, and ultraviolet B have been reported to induce remissions, but this awaits confirmation. Responses to colchicine, cyclosporine, and topical tacalcitol (1α-24R-dihydroxyvitamin D₃) have been anecdotally reported.

In two recalcitrant cases, rapid initial responses have been observed to infliximab. In one patient, remission could be maintained with acitretin, whereas the other relapsed despite continuation of infliximab.

 

 

Treatments for Sub-Corneal Pustular Dermatosis