AUTHOR AND EDITOR INFORMATION

Section 1 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Acknowledgments
• References

INTRODUCTION

Section 2 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Acknowledgments
• References

Background

Subcorneal pustular dermatosis was first described by Sneddon and Wilkinson in 1956. It is a rare, benign, chronic relapsing sterile pustular eruption typically involving the flexural sites of the trunk and proximal extremities. It most commonly affects woman aged 40 years or older. The etiology of this entity is unknown, and its exact nosologic classification is still controversial. Reports suggest that some cases of subcorneal pustular dermatosis represent a variant of pustular psoriasis. In addition to this, recent studies have identified a possible subgroup with autoantibodies, known as subcorneal pustular dermatosis type immunoglobulin A (IgA) pemphigus. Some authors consider this subgroup to be a rare variant of pemphigus rather than subcorneal pustular dermatosis.

Pathophysiology

The exact pathophysiology is unknown. The accumulation of neutrophils in the subcorneal layer suggests the presence of chemoattractants in the uppermost epidermis. Interleukin 8, leukotriene B4, and complement fragments C5a and C5a are neutrophil chemoattractants that have been found at increased levels in scale extracts of patients with subcorneal pustular dermatosis compared with that of controls. Tumor necrosis factor-alpha levels have been found to be significantly elevated in the serum and blister fluid of patients with subcorneal pustular dermatosis. The stimulus for these chemoattractants is unknown. No etiologic pathogen has been identified.

Frequency

International

Subcorneal pustular dermatosis is a rare condition. No estimate of prevalence or incidence is available. Cases are reported worldwide; no particular geographical predominance is apparent.

Mortality/Morbidity

Subcorneal pustular dermatosis is benign but chronic. The association of subcorneal pustular dermatosis with paraproteinemia or lymphoproliferative disorders, especially multiple myeloma, may alter the prognosis.

Race

No racial predisposition is reported.

Sex

Subcorneal pustular dermatosis affects women more commonly than men.

Age

Subcorneal pustular dermatosis is most common in individuals aged 40 years or older. It has been reported in children, but these cases tend to have atypical features more suggestive of psoriasis. Several reported cases of subcorneal pustular dermatosis in children have evolved into psoriasis.

CLINICAL

Section 3 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Acknowledgments
• References

History

• Patients typically present with a history of a relapsing pustular eruption involving the flexural areas of the trunk and proximal extremities. Individual pustular lesions arise within a few hours. Pruritus and irritation can occur but are not usually prominent symptoms. Systemic and toxic symptoms are not associated with acute episodes.
• Patients may present with histories notable for monoclonal gammopathies (IgA more often than immunoglobulin G), lymphoproliferative disorders (especially multiple myeloma), and pyoderma gangrenosum. These conditions are well-recognized associations with subcorneal pustular dermatosis (developing both before and after the diagnosis of subcorneal pustular dermatosis). Other anecdotally associated conditions include inflammatory bowel disease, rheumatoid arthritis, systemic lupus erythematosus, hyperthyroidism and hypothyroidism, APUDoma (amine precursor uptake and decarboxylation cell–derived tumor), polycythemia rubra vera, and SAPHO (synovitis, acne, pustulosis, osteitis) syndrome.
• Patients should be queried about a personal and family history of psoriasis because differentiating subcorneal pustular dermatosis from pustular psoriasis can be difficult. Similarly, patients should be questioned about recent drug exposure because acute generalized exanthematous pustulosis is also in the differential diagnosis.

Physical

• The primary lesions are flaccid pustules, measuring several millimeters in diameter, on normal or mildly erythematous skin.
• The classic lesion has been described as a "half-half" blister, in which purulent fluid accumulates in the lower half of the blister.
• The pustules can be isolated or grouped. They tend to coalesce and form annular, circinate, or serpiginous patterns. The pustules are superficial and rupture easily, resulting in a superficial crust.
• Mild hyperpigmentation often remains after pustular lesions have resolved.
• The most commonly affected areas include the axillae, groin, neck, and the submammary regions. The proximal flexural aspects of the extremities are sometimes affected.
• Palmar, plantar, face and mucous membrane involvement is unusual.

Causes

• The etiology is unknown. It is a sterile eruption. Ongoing controversy exists regarding the diagnosis of subcorneal pustular dermatosis. It might be a condition with more than one etiology.
• Some cases of subcorneal pustular dermatosis are argued to be a variant of pustular psoriasis. Note that clinical and histologic differentiation of subcorneal pustular dermatosis from psoriasis can be difficult or even impossible, although spongiform changes on histology favor the latter. Furthermore, a significant number of cases initially diagnosed as subcorneal pustular dermatosis are later diagnosed as psoriasis.
• Other cases of subcorneal pustular dermatosis are argued to be a rare variant of pemphigus, known as subcorneal pustular dermatosis type IgA pemphigus. This subgroup of patients show positive immunofluorescence with epidermal intercellular IgA deposits. The positive immunofluorescence can develop years after the initial diagnosis of subcorneal pustular dermatosis. Unlike pemphigus, a predominance of neutrophils and an absence or moderate acantholysis is observed; additionally, the condition is usually responsive to dapsone.

DIFFERENTIALS

Section 4 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Acknowledgments
• References

Other Problems to be Considered

Acute generalized exanthematous pustulosis
Annular pustular psoriasis
Dermatophytosis
Generalized pustular psoriasis of pregnancy
Necrolytic migratory erythema

WORKUP

Section 5 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Acknowledgments
• References

Lab Studies

• Serum protein electrophoresis
• • The association of paraproteinemia with subcorneal pustular dermatosis is well documented. One study showed 4 of 10 patients with subcorneal pustular dermatosis had a monoclonal gammopathy. Most reported cases have been with IgA monoclonal gammopathies, either kappa or lambda light-chain type. However, immunoglobulin G gammopathies are also reported.
  • Serum protein electrophoresis should be repeated periodically because the development of paraproteinemia can occur years after the initial eruption of subcutaneous pustular dermatosis. Furthermore, the increased risk of multiple myeloma in patients with a monoclonal gammopathy is well recognized.
  • Skeletal survey and bone marrow aspiration should be undertaken if multiple myeloma is suspected.
• Skin bacterial culture: Subcorneal pustular dermatosis is a sterile eruption. Impetigo and secondary bacterial infections should be excluded.
• Skin scraping and fungal culture: Dermatophyte infections need to be excluded.

Procedures

• Skin biopsy of an early lesion is needed for histologic analysis and direct immunofluorescence testing.

Histologic Findings

The classic histologic finding in subcorneal pustular dermatosis is subcorneal pustules composed primarily of neutrophils and occasional eosinophils. However, this finding is not specific for subcorneal pustular dermatosis and can be found in other conditions such as pustular psoriasis, acute generalized exanthematous pustulosis, pemphigus foliaceus, bacterial impetigo, and dermatophytosis. In subcorneal pustular dermatosis, unlike pustular psoriasis, the epidermis usually has minimal spongiosis. The dermis in subcorneal pustular dermatitis shows a perivascular infiltrate of neutrophils and occasional monocytes and eosinophils. Acantholysis is not prominent; however, it has been reported in older lesions.

Direct and indirect immunofluorescence studies are typically negative. Nevertheless, periodic repeat studies are recommended to detect epidermal intercellular IgA staining in order to identify a subgroup referred to as subcorneal pustular dermatosis type IgA pemphigus. Desmocollin-1 has been recognized as the autoantigen in this subgroup.

TREATMENT

Section 6 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Acknowledgments
• References

Medical Care

• Dapsone is the treatment of choice. The response is slower than that seen with dermatitis herpetiformis, with resolution usually occurring in about 4 weeks. Once disease control has been established, the dose should be tapered to the lowest dose needed to maintain control. Sulfapyridine and sulfamethoxypyridazine may also be used, but only a few isolated reports support their effectiveness.
• Acitretin (and formally etretinate) has been used to successfully treat subcorneal pustular dermatosis and should be considered an alternative or additional treatment for those who are intolerant of or unresponsive to dapsone. Once disease control has been established, the dose should be tapered to the lowest dose needed to maintain control. Isotretinoin at 0.5 mg/kg/d appears to be ineffective.
• Phototherapy with psoralen with UVA, broadband UVB, and narrowband UVB alone or in combination with dapsone and/or retinoids can be successful at controlling subcorneal pustular dermatosis. Long-term maintenance regimens may be needed.
• Anecdotal case reports support the use of infliximab, tacalcitol, mizoribine, ketoconazole, tetracycline, minocycline, benzylpenicillin, vitamin E, azithromycin, cyclosporine, colchicine, and adalimumab with mycophenolate mofetil.
• Systemic and topical corticosteroids are generally ineffective but may provide some control. They have been used in combination with dapsone to treat associated conditions such as pyoderma gangrenosum and multiple myeloma. A good response to systemic corticosteroids is atypical and is suggestive of a diagnosis of pustular psoriasis.

MEDICATION

Section 7 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Acknowledgments
• References

The goals of pharmacotherapy are to reduce morbidity and prevent complications.

Drug Category: Antibiotics

Empiric antimicrobial therapy must be comprehensive and should cover all likely pathogens in the context of the clinical setting.

Drug Category: Retinoids

Decrease cohesiveness of abnormal hyperproliferative keratinocytes and may reduce potential for malignant degeneration. Modulate keratinocyte differentiation. Have been shown to reduce risk of skin cancer formation in renal transplant patients.

FOLLOW-UP

Section 8 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Acknowledgments
• References

Further Outpatient Care

• Long-term follow-up is recommended.
• • Periodic evaluations with serum protein electrophoresis and direct immunofluorescence should be performed every few years.
  • Paraproteinemia, myeloma, intraepidermal IgA staining, and pustular psoriasis may develop several years after the initial presentation of subcorneal pustular dermatosis. Identifying these conditions, and other associated diagnoses, can improve our understanding of the etiology and pathogenesis of subcorneal pustular dermatosis, clarify its relationship with IgA pemphigus and pustular psoriasis, and help define its nosologic classification.

Prognosis

• Subcorneal pustular dermatosis is chronic and relapsing, but benign.

ACKNOWLEDGMENTS

Section 9 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Acknowledgments
• References

The authors and editors of eMedicine gratefully acknowledge the contributions of previous authors, Dr. John D Wilkinson and Dr. John Reed, to the development and writing of this article.

REFERENCES

Section 10 of 10

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Acknowledgments
• References

• Ayres S, Mihan R. Letter: Subcorneal pustular dermatosis controlled by vitamin E. Arch Dermatol. Jun 1974;109(6):914. [Medline].
• Baker H. ...Or does it?. Am J Dermatopathol. 1981;3:384.
• Bauwens M, De Coninck A, Roseeuw D. Subcorneal pustular dermatosis treated with PUVA therapy. A case report andreview of the literature. Dermatology. 1999;198(2):203-5. [Medline].
• Bliziotis I, Rafailidis P, Vergidis P, Falagas ME. Regression of subcorneal pustular dermatosis type of IgA pemphigus lesions with azithromycin. J Infect. Aug 2005;51(2):E31-4. [Medline].
• Butt A, Burge SM. Sneddon-Wilkinson disease in association with rheumatoid arthritis. Br J Dermatol. Feb 1995;132(2):313-5. [Medline].
• Chimenti S, Ackerman AB. Is subcorneal pustular dermatosis of Sneddon and Wilkinson an entity sui generis?. Am J Dermatopathol. Winter 1981;3(4):363-76. [Medline].
• Grob JJ, Mege JL, Capo C, et al. Role of tumor necrosis factor-alpha in Sneddon-Wilkinson subcorneal pustular dermatosis. A model of neutrophil priming in vivo. J Am Acad Dermatol. Nov 1991;25(5 Pt 2):944-7. [Medline].
• Hashimoto T, Kiyokawa C, Mori O, et al. Human desmocollin 1 (Dsc1) is an autoantigen for the subcorneal pustular dermatosis type of IgA pemphigus. J Invest Dermatol. Aug 1997;109(2):127-31. [Medline].
• Howell SM, Bessinger GT, Altman CE, Belnap CM. Rapid response of IgA pemphigus of the subcorneal pustular dermatosis subtype to treatment with adalimumab and mycophenolate mofetil. J Am Acad Dermatol. Sep 2005;53(3):541-3. [Medline].
• Kasha EE, Epinette WW. Subcorneal pustular dermatosis (Sneddon-Wilkinson disease) in association with a monoclonal gammopathy: A report and review of the literature. J Am Acad Dermatol. 1998;19:854-8. [Medline].
• Kawaguchi M, Mitsuhashi Y, Kondo S. A case of subcorneal pustular dermatosis treated with tacalcitol (1alpha,24-dihydroxyvitaminD3). J Dermatol. Oct 2000;27(10):669-72. [Medline].
• Kono T, Terashima T, Oura H, et al. Recalcitrant subcorneal pustular dermatosis and bullous pemphigoid treated with mizoribine, an immunosuppressive, purine biosynthesis inhibitor. Br J Dermatol. Dec 2000;143(6):1328-30. [Medline].
• Lin RY, Schwartz RA, Lambert WC. Subcorneal pustular dermatosis with polyarthritis. Cutis. Feb 1986;37(2):123-4, 126. [Medline].
• Lutz ME, Daoud MS, McEvoy MT, Gibson LE. Subcorneal pustular dermatosis: a clinical study of ten patients. Cutis. Apr 1998;61(4):203-8. [Medline].
• Mandel EH, Gonzales V. Subcorneal pustular dermatosis (Sneddon-Wilkinson). Arch Dermatol. Feb 1969;99(2):246-7. [Medline].
• Marlière V, Beylot-Barry M, Beylot C, Doutre M. Successful treatment of subcorneal pustular dermatosis (Sneddon-wilkinson disease) by acitretin: report of a case. Dermatology. 1999;199(2):153-5. [Medline].
• Orton DI, George SA. Subcorneal pustular dermatosis responsive to narrowband (TL-01) UVB phototherapy. Br J Dermatol. Jul 1997;137(1):149-50. [Medline].
• Pinkus H. Is subcorneal pustular dermatosis of Sneddon and Wilkinson and entity sui generis?. Am J Dermatopathol. Winter 1981;3(4):379-80. [Medline].
• Reed J, Wilkinson J. Subcorneal pustular dermatosis. Clin Dermatol. May-Jun 2000;18(3):301-13. [Medline].
• Ryan TJ. Sneddon and Wilkinson''s pustular dermatosis does exist... Am J Dermatopathol. Winter 1981;3(4):383-4. [Medline].
• Sanchez NP, Perry HO, Muller SA. On the relationship between subcorneal pustular dermatosis and pustular psoriasis. Am J Dermatopathol. Winter 1981;3(4):385-6. [Medline].
• Scerri L, Zaki I, Allen BR. Pyoderma gangrenosum and subcorneal pustular dermatosis, without monoclonal gammopathy. Br J Dermatol. Mar 1994;130(3):398-9. [Medline].
• Sneddon I, Wilkinson DS. Subcorneal pustular dermatosis differs from subcorneal pustulosis. Am J Dermatopathol. Winter 1981;3(4):377. [Medline].
• Sneddon IB, Wilkinson DS. Subcorneal pustular dermatosis. Br J Dermatol. Dec 1956;68(12):385-94. [Medline].
• Sneddon IB, Wilkinson DS. Subcorneal pustular dermatosis. Br J Dermatol. Jan 1979;100(1):61-8. [Medline].
• Tagami H, Iwatsuki K, Iwase Y, Yamada M. Subcorneal pustular dermatosis with vesiculo-bullous eruption. Demonstration of subcorneal IgA deposits and a leukocyte chemotactic factor. Br J Dermatol. Nov 1983;109(5):581-7. [Medline].
• Takata M, Inaoki M, Shodo M, et al. Subcorneal pustular dermatosis associated with IgA myeloma and intraepidermal IgA deposits. Dermatology. 1994;189 Suppl 1:111-4. [Medline].
• Takematsu H, Tagami H. Quantification of chemotactic peptides (C5a anaphylatoxin and IL-8) in psoriatic lesional skin. Arch Dermatol. 1993;129:74-80. [Medline].
• Verma KK, Pasricha JS. Ketoconazole as a therapeutic modality in subcorneal pustular dermatosis. Acta Derm Venereol. Sep 1997;77(5):407-8. [Medline].
• Voigtländer C, Lüftl M, Schuler G, Hertl M. Infliximab (anti-tumor necrosis factor alpha antibody): a novel, highly effective treatment of recalcitrant subcorneal pustular dermatosis (Sneddon-Wilkinson disease). Arch Dermatol. Dec 2001;137(12):1571-4. [Medline].
• Wallach D, Cottenot F, Pelbois G, et al. Subcorneal pustular dermatosis and monoclonal IgA. Br J Dermatol. Aug 1982;107(2):229-34. [Medline].
• Wallach D. Intraepidermal IgA pustulosis. J Am Acad Dermatol. Dec 1992;27(6 Pt 1):993-1000. [Medline].
• Zachariae CO, Rossen K, Weismann K. An unusual severe case of subcorneal pustular dermatosis treated with cyclosporine and prednisolone. Acta Derm Venereol. Sep-Oct 2000;80(5):386-7. [Medline].

Article Last Updated: Mar 10, 2006