Complete remission of skin lesions in a patient with subcorneal pustular dermatosis (Sneddon–Wilkinson disease) treated with antimyeloma therapy: association with disappearance of M‐protein

Subcorneal pustular dermatosis (SPD), or Sneddon–Wilkinson disease, is a rare pustular skin disease that follows a chronic relapsing course. A well‐known association exists between SPD and IgA monoclonal gammopathy of undetermined significance (MGUS), which exists in up to 40% of cases. SPD has also been observed in patients with IgA myeloma. In SPD, direct and indirect immunofluorescence studies do not reveal in vivo bound IgA to the epithelial cell surface, in contrast to IgA pemphigus, which has similar clinicopathological features. Here we describe the case of a male patient with SPD and a concurrent IgA MGUS who had been treated with dapsone for 20 years with frequent relapses. Following development of multiple myeloma, the patient was treated with intensive antimyeloma treatment consisting of high‐dose melphalan with autologous stem cell transplantation. This resulted in a complete remission of the myeloma with disappearance of the M‐protein. In addition, a sustained remission of SPD was achieved without further treatment. Twenty‐eight months after melphalan therapy the M‐protein reappeared in the serum, and 2 months later SPD reappeared with histopathologically proven skin lesions at predilection sites. Presence and absence of skin lesions was found to correlate with the presence and absence of the M‐protein in the serum. This is the first report of antimyeloma therapy inducing a long‐lasting remission in SPD. The findings in this patient strongly suggest a causal role for circulating IgA antibodies in the pathogenesis of SPD. Antimyeloma treatment should be considered in patients with IgA MGUS‐associated SPD refractory to other therapies.     

Subcorneal Pustular Dermatosis: A Review of 30 Years of Progress

Subcorneal pustular dermatosis (SPD), also known as Sneddon–Wilkinson disease, is a rare, benign yet relapsing pustular dermatosis. Its incidence and prevalence have not been well studied. It characteristically presents as hypopyon pustules on the trunk and intertriginous areas of the body. SPD is similar to two other disease entities. Both SPD-type immunoglobulin (Ig)-A pemphigus and annular pustular psoriasis clinically and histologically present similarly to SPD. Immunologic studies separate SPD-type IgA pemphigus from SPD and pustular psoriasis. However, there is still an unclear designation as to whether SPD is its own entity distinct from pustular psoriasis, as the once thought characteristic histologic picture of psoriasis does not hold true for pustular psoriasis. SPD has been reported to occur in association with several neoplastic, immunologic, and inflammatory conditions. Dapsone remains the first-line treatment for SPD, although dapsone-resistant cases have been increasingly reported. Other therapies have been used singly or as adjunctive therapy with success, such as corticosteroids, immunosuppressive agents, tumor necrosis factor inhibitors, and ultraviolet light therapy. This article provides a review of the last 30 years of available literature, with a focus on successful treatment options and a suggestion for reappraisal of the classification of SPD.     

Subcorneal pustular dermatosis treated with PUVA therapy. A case report and review of the literature.

BACKGROUND: Subcorneal pustular dermatosis (SPD) is a chronic recurrent pustular dermatosis of unknown etiology. Many treatments have been proposed, none of which has been uniformly successful. OBJECTIVE: Our purpose is to report a patient with SPD successfully treated by PUVA and to review the literature concerning phototherapy treatment of SPD. METHODS: A patient suffering from SPD resistant to diaminodiphenylsulphone (dapsone) responded well to a combination therapy consisting of dapsone and PUVA. He received 50 mg/day and 3 PUVA sessions a week. Photographs were taken at baseline and after 15 sessions. RESULTS: The lesions were virtually cleared after 15 sessions. The patient remained free of lesions with a maintenance therapy of dapsone (50 mg/ day) and 1 PUVA session a week. CONCLUSION: The therapeutic value of phototherapy for the treatment of SPD still has to be confirmed and could be a valuable alternative for treatment-resistant patients.     

Neutrophilic Dermatoses

Sweet syndrome, pyoderma gangrenosum, and subcorneal pustular dermatosis are neutrophilic dermatoses – conditions that have an inflammatory infiltrate consisting of mature polymorphonuclear leukocytes. The neutrophils are usually located within the dermis in Sweet syndrome and pyoderma gangrenosum; however, in subcorneal pustular dermatosis, they are found in the upper layers of the epidermis. Sweet syndrome, also referred to as acute febrile neutrophilic dermatosis, is characterized by pyrexia, elevated neutrophil count, painful erythematous cutaneous lesions that have an infiltrate of mature neutrophils typically located in the upper dermis, and prompt clinical improvement following the initiation of systemic corticosteroid therapy. Classical, malignancy-associated, and drug-induced variants of Sweet syndrome exist. Pyoderma gangrenosum is characterized by painful, enlarging necrotic ulcers with bluish undermined borders surrounded by advancing zones of erythema; its clinical variants include: ulcerative or classic, pustular, bullous or atypical, vegetative, peristomal, and drug-induced. Subcorneal pustular dermatosis is an uncommon relapsing symmetric pustular eruption that involves flexural and intertriginous areas; it can be idiopathic or associated with cancer, infections, medications, and systemic diseases. Since Sweet syndrome, pyoderma gangrenosum, and subcorneal pustular dermatosis share not only the same inflammatory cell but also similar associated systemic diseases, it is not surprising that the concurrent or sequential development of these neutrophilic dermatoses has been observed in the same individual. Also, it is not unexpected that several of the effective therapeutic interventions – including systemic drugs, topical agents, and other treatment modalities – for the management of these dermatoses are the same. The treatment of choice for Sweet syndrome and idiopathic pyoderma gangrenosum is systemic corticosteroids; however, for subcorneal pustular dermatosis, dapsone is the drug of choice. Yet, tumor necrosis factor-α antagonists are becoming the preferred choice when pyoderma gangrenosum is accompanied by inflammatory bowel disease or rheumatoid arthritis. Potassium iodide and colchicine are alternative first-line therapies for Sweet syndrome and indomethacin (indometacin), clofazimine, cyclosporine (ciclosporin), and dapsone are second-line treatments. Cyclosporine is effective in the acute management of pyoderma gangrenosum; however, when tapering the drug, additional systemic agents are necessary for maintaining the clinical response. In some patients with subcorneal pustular dermatosis, systemic corticosteroids may be effective; yet, systemic retinoids (such as etretinate and acitretin) have effectively been used for treating this neutrophilic dermatosis – either as monotherapy or in combination with dapsone or as a component of phototherapy with psoralen andUVAradiation. Topical agents can have an adjuvant role in themanagement of these neutrophilic dermatoses; however, high-potency topical corticosteroids may successfully treat localized manifestations of Sweet syndrome, pyoderma gangrenosum, and subcorneal pustular dermatosis. Intralesional corticosteroid therapy for patients with Sweet syndrome and pyoderma gangrenosum, hyperbaric oxygen and plasmapheresis for patients with pyoderma grangrenosum, and phototherapy for patients with subcorneal pustular dermatosis are other modalities that have been used effectively for treating individuals with these neutrophilic dermatoses.     

Apudoma and subcorneal pustular dermatosis (Sneddon-Wilkinson disease).

The subcorneal pustular dermatosis (SPD) is a rare dermatosis. IgA monoclonal gammapathy is the most frequently associated disease with the SPD. We report a case of SPD in a patient with metastatic apudoma, an association not previously described. The rare nature of both diseases suggests that this association is not fortuitous.     

Pyoderma gangrenosum associated with subcorneal pustular dermatosis and IgA myeloma

We report a 57-year-old woman with a 12-year history of ulcerative pyoderma gangrenosum (PG). Five years after the onset of PG, she developed subcorneal pustular dermatosis (SPD) and biclonal IgA and IgG gammopathy. She developed PG at two bone-marrow biopsy sites, showing pathergy. Finally, she developed multiple myeloma. Although PG and SPD may occur without associated underlying malignancy, these patients should be followed up for any prospective malignancy because of the association between these disorders.     

The expanding spectrum of IgA pemphigus: a case report and review of the literature

IgA pemphigus (IGAP) is a rare, distinct variant of pemphigus, currently classified, depending upon the histological features, immunofluorescence staining pattern and autoantibody profile, into two types: subcorneal pustular dermatosis (SPD) and intraepidermal neutrophilic IgA dermatosis. In a patient with a widespread blistering disease of the skin resembling SPD‐type IGAP, we demonstrate the coexistence of IgA reactivity to both epidermal (desmocollins 2 and 3) and basement membrane‐associated (BP180) proteins, suggesting the coexistence of atypical IGAP and linear IgA bullous dermatosis, respectively. This case, together with 20 previous reports of atypical IGAP, underscores the limitations of current classification schemes. Therefore, we suggest reclassifying these cases under the general term ‘IGAP spectrum’.     

Erosive pustular dermatosis of the scalp: causes and treatments

Erosive pustular dermatosis of the scalp is a rare condition which primarily affects older women after local trauma and has historically been treated with topical steroids. As it is a rare entity and resembles other dermatologic conditions, it may easily be misdiagnosed. Identifying the causes and evaluating the efficacy of treatments of erosive pustular dermatosis of the scalp (EPDS) is of great importance to both avoid misdiagnosis and ensure optimal treatment of this rare condition. There are numerous causes. In addition to surgeries and physical injuries, topical and procedural treatments for actinic keratoses and androgenetic alopecia can trigger the development of lesions. There are also documented associations with several autoimmune and systemic conditions. Besides corticosteroids, topical tacrolimus and photodynamic therapy were the most commonly used treatments for EPDS. They were effective with few recurrences and adverse effects. Other successful treatment options were topical dapsone, silicone gels, calcipotriol, acitretin, and isotretinoin. Oral dapsone can be used in cases of disseminated disease. Zinc sulfate should be considered with low‐serum zinc levels. While cyclosporine was effective, there were adverse effects that may limit its use. It is important for dermatologists to be aware of the wide array of potential causes of erosive pustular dermatosis and include it on their differential. Additionally, although high‐potency topical steroids have been historically used as the first‐line treatment, there are many other effective treatments that may avoid recurrence and skin atrophy, particularly in the elderly population.     

Intercellular IgA dermatosis (IgA pemphigus)--two cases illustrating the clinical heterogeneity of this disorder

IgA pemphigus is rare but may be underdiagnosed. We describe two cases, a 50-year-old female with a pustular eruption resembling subcorneal pustular dermatosis and a 55-year-old male with a pruritic vesiculopustular eruption simulating dermatitis herpetiformis. They illustrate the clinical heterogeneity of IgA pemphigus which is likely to reflect differences in autoantigens, analogous to pemphigus vulgaris and pemphigus foliaceus. There is now evidence that IgA pemphigus encompasses at least two subgroups: a subcorneal pustular dermatosis (SPD)-type, (see case 1) characterized by subcorneal pustules and autoantibodies to desmocollin 1; and intra-epidermal neutrophilic dermatosis (IEN)-type cases (see case 2) which show intra-epidermal pustules and in whom the autoantigen may be desmoglein 3, the pemphigus vulgaris antigen.     

Sneddon-Wilkinson disease resistant to dapsone and colchicine successfully controlled with PUVA

A 28-year-old man with a 6-year history of subcorneal pustular dermatosis (SPD) is presented. This case reviews the clinical features, differential diagnosis, etiology, and treatment options of SPD. In particular, this case emphasizes the absence of response to dapsone and colchicine and control with PUVA therapy.     

Distinguishing annular pustular psoriasis from subcorneal pustular dermatosis—A diagnostic dilemma in a 10-year-old boy

Subcorneal pustular dermatosis (SPD) and annular pustular psoriasis (APP) are very rare in childhood and difficult to differentiate both clinically and histopathologically. We report the case of a 10-year-old male with a 9-year history of erythematous scaly annular plaques with scattered pustules on the trunk. Although initially diagnosed as SPD, a lack of response to dapsone, presence of spongiosis on histology, and early age of disease onset led to consideration of APP. The patient was subsequently treated with adalimumab 80 mg weekly and completely cleared. This case illustrates the overlapping features of SPD and APP and suggests that the two disorders may represent a spectrum of the same disease.     

Dermatosis pustulosa subcórnea en un paciente con espondilitis anquilosante

—We present the case of a 33-year-old patient, diagnosed with ankylosing spondylitis 12 years before, who came to our practice after having had skin symptoms consistent with subcorneal pustular dermatosis (SPD) for a month. Although SPD is considered a purely cutaneous disease, associations with other entities have been described. We describe a case of SPD appearing along with a 12-year case of ankylosing spondylitis, and we review the literature of cases described to date associated or simultaneous with SPD.     

Dermatosis pustulosa subcórnea con anticuerpos IgA antidesmocolina

—The case of a 74-year-old patient with cutaneous lesions characteristic of subcorneal pustular dermatosis (SPD) is reported. Indirect immunofluorescence revealed intercellular IgA deposition in the upper layers of the epidermis, and we demonstrated that the antigen recognized by these autoantibodies was desmocollin 1 (protein present in the desmosome extracelular portion).In the last years, a new variant of pemphigus has been defined, IgA pemphigus, which presents under two diferent forms: SPD and neutrophilic intraepidermal dermatosis. Clinical and histological differential diagnosis of the patient herein reported is commented with special emphasis in the differentiation between SPD and pustular psoriasis.     

IgA antikeratinocyte surface autoantibodies from two types of intercellular IgA vesiculopustular dermatosis recognize distinct isoforms of desmocollin

We previously proposed the term intercellular IgA vesiculopustular dermatosis (IAVPD) for cases showing IgA antikeratinocyte surface autoantibodies. This condition is divided into two subtypes: intraepidermal neutrophilic IgA dermatosis (IEN), showing pustule formation in the entire epidermis, and subcorneal pustular dermatosis (SPD) showing pustule formation in the uppermost epidermis. We have previously reported that serum from certain IAVPD patients reacts with bovine desmocollin (Dsc), a desmosomal cadherin. In this study we showed that two Dsc isoforms with a slightly different molecular weight were recognized by the serum from these patients. Further analysis revealed that serum from patients with the SPD type, which stained the cell surface in the uppermost epidermis with immunofluorescence, seem to react with Dsc1. By contrast, serum from patients with the IEN type, which stained the cell surface at all levels of the epidermis with immunofluorescence, seemed to react with Dsc3. This difference of distribution between the two distinct Dsc molecules may contribute to the different clinicopathological features between the IEN and SPD type of IAVPD.     

Two Brazilian cases of IgA pemphigus

IgA pemphigus is a rare, neutrophilic, acantholytic skin disorder with approximately 70 cases described in the literature. We report two patients with the subcorneal pustular dermatosis (SPD) type of IgA pemphigus. Initially, both patients were misdiagnosed as subcorneal pustular dermatosis of Sneddon and Wilkinson. The correct diagnosis was only made after detecting intercellular IgA depositions in the epidermis by direct immunofluorescence. Immunoblotting (IB) of normal human epidermal extracts, performed on both sera, was negative for Dsg 1, Dsg 3, BP 230, BP 180, 210 kDa envoplakin, and 190 kDa periplakin. ELISA for desmogleins (Dsg 1 and Dsg 3) showed that neither of the cases had IgA antibodies to Dsg. The c-DNA transfection test for desmocollins (Dsc) revealed that the IgA antibodies of both patients reacted with desmocollin 1. This result supports the hypothesis that the autoantigen in SPD type IgA pemphigus is desmocollin 1.     

Subcorneal Pustular Dermatosis (Sneddon-Wilkinson Disease) with Absence of Desmoglein 1 and 3 Antibodies

Subcorneal pustular dermatosis (SPD) [Sneddon-Wilkinson disease] is a benign and uncommon disorder characterized by a chronic, relapsing vesiculopustular eruption of unknown etiology. We present a case of SPD in a young Black woman in whom ELISA was performed to test for desmoglein 1 and 3 antigens (the first reported case of evaluation for these antigens in a patient with SPD). The test revealed the absence of both antibodies. The patient was successfully treated with topical corticosteroids and narrow-band UVB phototherapy. In this report, we review both the pathophysiology of SPD, which has yet to be clarified, and its treatment. Data obtained from our case report add further support to the hypothesis that a non-antibody-mediated mechanism is operative in SPD. The treatment of choice for SPD is dapsone. However, the combination of corticosteroids and UVB phototherapy should be considered a valid therapeutic option in patients who are not appropriate candidates for dapsone therapy.     

Neutrophilic dermatoses as systemic diseases

Neutrophilic dermatoses (ND) are inflammatory skin conditions characterized by a sterile infiltrate of normal polymorphonuclear leukocytes. The main clinical forms of ND include Sweet syndrome, pyoderma gangrenosum, erythema elevatum diutinum, subcorneal pustular dermatosis, and their atypical or transitional forms. ND are often idiopathic, but they may be associated with myeloid hematologic malignancies (Sweet syndrome), inflammatory bowel disease or rheumatoid arthritis (pyoderma gangrenosum), and monoclonal gammopathies (erythema elevatum diutinum, subcorneal pustular dermatosis). The possible infiltration of internal organs with neutrophils during the setting of ND underlies the concept of a neutrophilic systemic disease. ND may be seen as a polygenic autoinflammatory syndrome due to their frequent association with other autoinflammatory disorders (monogenic or polygenic) and the recent published efficacy of interleukin-1 blocking therapies in their management.     

Subcorneal pustular dermatosis (Sneddon-Wilkinson disease) with amicrobial lymph node suppuration and aseptic spleen abscesses

Subcorneal pustular dermatosis (SPD) or Sneddon-Wilkinson disease is a skin eruption in which concomitant systemic involvement has not been reported to our knowledge. We describe a patient suffering from SPD of 6 years duration with amicrobial inguinal lymph node suppuration and aseptic spleen abscesses followed by pyoderma gangrenosum.     

Subcorneal pustular dermatosis with polyarthritis

A 19-year-old man experienced the acute onset of subcorneal pustular dermatosis (SPD), fever, and a symmetrical polyarthritis. The association of SPD with acute polyarthritis is rare.     

Pustular skin disorders: diagnosis and treatment

The differential diagnosis for pustular skin disorders is extensive. The distribution of the lesions and the age of the patient are characteristics that may provide strong clues to the etiology of cutaneous pustular eruptions. In adults, generalized pustular dermatoses include pustular psoriasis, Reiter's disease and subcorneal pustular dermatosis. Medications can cause generalized pustular eruptions, such as in the case of acute generalized exanthematous pustulosis; or more localized reactions, such as acneiform drug eruptions, which usually involve the face, chest and back. Localized pustular eruptions are seen on the hands and feet in adults with pustulosis palmaris et plantaris and acrodermatitis continua (both of which may be variants of psoriasis); on the face in patients with acne vulgaris, rosacea, and perioral dermatitis; and on the trunk and/or extremities in patients with folliculitis. A separate condition known as eosinophilic folliculitis occurs in individuals with advanced human immunodeficiency disease. Severely pruritic, sterile, eosinophilic pustules are found on the chest, proximal extremities, head and neck. Elevated serum immunoglobulin E and eosinophilia are often concurrently found. In neonates, it is especially important to make the correct diagnosis with respect to pustular skin disorders, since pustules can be a manifestation of sepsis or other serious infectious diseases. Generalized pustular eruptions in neonates include erythema toxicum neonatorum and transient neonatal pustular melanosis, both of which are non-infectious. Pustules are seen in infants with congenital cutaneous candidiasis, which may or may not involve disseminated disease. Ofuji's syndrome is an uncommon generalized pustular dermatosis of infancy with associated eosinophilia. As in adults, neonates and infants may develop acne or scabies infestations. In this article, we review the most common pustular dermatoses and offer a systematic approach to making a diagnosis. We also report the most up-to-date information on the treatment of these various cutaneous pustular conditions.