Are You Confident of the Diagnosis?

What you should be alert for in the history

Sneddon-Wilkinson disease, also known as subcorneal pustular dermatosis, is a rare disorder which may occur in both genders and across all age groups, but has been described most often in women 40 years of age and older. It is chronic in nature, classically manifesting with annular and serginous arrays of superficial pustules, localized to intertriginous and flexural sites of the body, as well as the abdomen.

Sneddon-Wilkinson has been commonly associated with several conditions, namely benign monoclonal gammopathies (often IgA type), multiple myeloma and other lymphoproliferative conditions, and pyoderma gangrenosum. It has also been linked in reports to a number of other disorders, including systemic lupus erythematosus, rheumatoid arthritis, multiple sclerosis, Sjögren’s, aplastic anemia, and hypo- and hyperthyroidism.

Characteristic findings on physical examination

On physical examination, multiple 1-3mm fragile pustules are observed in the axillae, inframammary regions, inguinal folds, flexural aspects of the extremities, and trunk. The primary lesions often coalesce in these areas, and may be grouped in annular and/or serpiginous configurations. Eventual rupture of the pustules leaves behind collarettes of scale (Figure 1). Mucosal sites are rarely involved.

Figure 1.

Collarettes of scale following rupture of intact pustules, inframammary fold.

Expected results of diagnostic studies

Histopathology demonstrates collections of neutrophils, grouped just below the stratum corneum; the occasional eosinophil may be observed as well. While spongiform pustules in the epidermis may sometimes be found in Sneddon-Wilkinson, this finding is far more characteristic of a closely related condition, pustular psoriasis. Foci of acantholysis may be observed in Sneddon-Wilkinson. Finally, a superficial perivascular mixed inflammatory infiltrate wtih neutrophils is often found in the dermis underlying the subcorneal pustules.

Direct immunofluorescence (DIF) is negative for IgA in the epidermis. A positive DIF demonstrating the presence of intercellular IgA in the setting of a subcorneal pustule on histopathology should indicate a diagnosis of the subcorneal pustular dermatosis type of IgA pemphigus, rather than simply subcorneal pustular dermatosis/Sneddon-Wilkinson. Bacterial and fungal cultures in Sneddon-Wilkinson are negative, as this is a condition of sterile pustulosis.

Diagnosis confirmation

The differential diagnosis for Sneddon-Wilkinson disease includes the follow entities:

• - pustular psoriasis

• - impetigo herptiformis (also known as pustular psoriasis of pregnancy)

• - acute generalized exanthematous pustulosis (AGEP)

• - IgA pemphigus

• - bacterial impetigo

• - dermatophytosis

Morphologically, pustular psoriasis and AGEP may be difficult to distinguish from Sneddon-Wilkinson. A diagnosis of pustular psoriasis may be suggested based on personal or family history of psorasis. Furthermore, while both pustular psorasis and Sneddon-Wilkinson tend localize to intertriginous sites, the former also often involves acral sites and nailbeds.

AGEP is precipitated most often by antecedent ingestion of medications, particularly ß-lactam and macrolide antibiotics, and is frequently accompanied by fever, neutrophilia (90%), and eosinophilia (30%).

Who is at Risk for Developing this Disease?

Sneddon-Wilkinson disease is rare, and the exact prevalence or incidence of the disease is unknown. On the basis of published reports, it occurs more often in women than men, typically in the fifth decade or later.

What is the Cause of the Disease?

Etiology

Pathophysiology

The etiology and pathophysiology of Sneddon-Wilkinson are largely unknown. Increased levels of TNF-alpha have been found in the blister fluid and serum of patients with Sneddon-Wilkinson. TNF-alpha has therefore been suggested as a neutrophil chemotactic factor, and anecdotal reports have cited improvement of disease with treatment using TNF-alpha inhibitors.

C5a and interleukin-8 were found in scale extracts from Sneddon-Wilkinson patients; these have also been proposed to function as neutrophil chemoattractants in the condition.

Systemic Implications and Complications

Serum and urine protein electrophoresis should be performed if the diagnosis of Sneddon-Wilkinson is suspected, in order to rule out the presence of multiple myeloma. It is also important to realize that patients with benign monoclonal gammopathies have an increased risk of developing multiple myeloma, and in such patients periodic repeat serum protein electrophoresis (SPEP) and urine protein electrophoresis (UPEP) testing should be considered.

There are no systemic complications attributed to Sneddon-Wilkinson itself.

Treatment Options

Treatment options are summarized in Table I.

Table I.

Treatment options for Sneddon-Wilkinson disease.

Optimal Therapeutic Approach for this Disease

Dapsone is the treatment of choice for Sneddon-Wilkinson, at doses of 25-200mg daily. Resolution of the eruption on dapsone typically occurs within 4 weeks. Subsequently, the medication should be tapered to the lowest dose necessary to maintain clearance. Discontinuation of dapsone therapy may result in relapse.

Acitretin and, previously, etretinate (now no longer marketed) have been reported to be beneficial for Sneddon-Wilkinson, although isotretinoin has not. Similarly, phototherapy (narrowband ultraviolet B [UVB] and psoralen and ultraviolet A [PUVA]) was found to be successful in several cases. Combination therapy using low-dose acitretin and narrowband UVB may be an effective treatment regimen.

Systemic corticosteroids are generally not as effective as dapsone, but several cases of successful treatment have been documented in the literature. Both infliximab and etanercept have been used with benefit as monotherapy in a few isolated cases of refractory Sneddon-Wilkinson disease. However, in one case, improvement was observed initially after starting infliximab, followed by worsening of the eruption after 12 weeks of therapy.

In milder cases, high potency and superpotent topical steroids (fluocinonide, clobetasol propionate) may be used to affected areas, although in the characteristic intertriginous sites, lower potency steroids are preferred (desonide, triamcinolone 0.025%, aclometasone). Antibiotics (tetracycline, minocycline) may also be employed, with good results. Topical dapsone may also be considered, alone or in combination with other medications.

Patient Management

Patients should be counseled that while Sneddon-Wilkinson is a benign condition, it is chronic and relapsing in nature. As a result, long-term treatment regimens may be necessary, and complete remission may be difficult to achieve in recalcitrant cases. Patients with mild disease may be seen every 3 to 6 months while the disease is active, but patients requiring systemic treatment such as dapsone or acitretin should be seen as often as needed for appropriate monitoring on the particular medication.

Given the association with monoclonal gammopathies including multiple myeloma, SPEP and UPEP testing should be performed at the time of initial diagnosis. In addition, yearly repeat SPEP and UPEP testing should be considered because monoclonal gammopathies may appear after initial diagnosis and patients with known benign gammopathies are at increased risk of developing multiple myeloma.

Unusual Clinical Scenarios to Consider in Patient Management

Sneddon-Wilkinson disease may easily be confused with pustular psoriasis. Treatment with dapsone may be a helpful diagnostic tool, since Sneddon-Wilkinson tends to respond well to the medication while pustular psoriasis often does not.