Subcorneal Pustular Dermatosis Research Articles

Review of Literature on Amicrobial Pustulosis of the Folds Associated with Autoimmune Disorders

Amicrobial pustulosis of the folds (APF) is characterized by relapsing, primary aseptic, pustular eruptions mainly affecting the cutaneous folds, scalp, and periorificial regions such as the mouth, external ear canal, and nostrils. APF is a rare condition that has previously been reported in 25 women exhibiting a wide spectrum of autoimmune abnormalities, particularly systemic lupus erythematosus. Histology of the skin lesions usually shows spongiform pustulation in the upper layer of the epidermis and a polymorphonuclear infiltrate in the dermis. APF must be differentiated from other noninfectious pustular diseases such as subcorneal pustulosis (Sneddon-Wilkinson disease) and pustular forms of psoriasis. APF should be included in the spectrum of reactive neutrophilic dermatoses, even though the exact pathomechanisms remain obscure. However, the striking female predominance may be of pathogenetic significance. Based on the small number of previously reported patients, the most effective therapy seems to be medium-dose systemic corticosteroids.

Off-Label Dermatologic Uses of Anti-TNF-a Therapies

Tumor necrosis factor-alpha (TNF-a) is a proinflammatory cytokine that plays an immunomodulatory role in a variety of systemic and dermatologic diseases. Currently, three anti-TNF-a drugs are available in North America- infliximab (approved in the U.S. for the treatment of rheumatoid arthritis, Crohn's disease, ankylosing spondylitis, ulcerative colitis, and psoriatic arthritis), etanercept (approved in the U.S. for the treatment of rheumatoid arthritis, juvenile rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, and psoriasis), and adalimumab (approved for the treatment of rheumatoid arthritis and psoriatic arthritis). To review the current literature supporting alternative (and currently off-label) dermatologic uses of TNF-a antagonists. A MEDLINE search (1966-March 2005) was conducted using the keywords "infliximab," "etanercept," "adalimumab," "TNF inhibitors," and "off-label" to identify published reports of off-label dermatologic uses of TNF-a inhibitors. Anti-TNF-a therapies have been reported in the following dermatologic diseases: sarcoidosis, hidradenitis suppuritiva, cicatricial pemphigoid, Behçet's disease, pyoderma gangrenosum, multicentric reticulohistiocytosis, apthous stomatitis, Sneddon-Wilkinson disease, SAPHO syndrome, pityriasis rubra pilaris, eosinophilic fasciitis, panniculitis, Crohn's disease, necrobiosis lipoidica diabeticorum, dermatomyositis, and scleroderma. The vast majority of these reports are in the form of individual case reports and small case series. Only two published randomized controlled trials involving the off-label use of a TNF inhibitor were found. A growing number of published reports suggest that anti-TNF-a therapies may be effective in the treatment of numerous inflammatory skin diseases outside their currently approved indications.

Off-Label Dermatologic Uses of Anti-TNF-a Therapies

Background: Tumor necrosis factor-alpha (TNF-a) is a proinflammatory cytokine that plays an immunomodulatory role in a variety of systemic and dermatologic diseases. Currently, three anti-TNF-a drugs are available in North America— infliximab (approved in the U.S. for the treatment of rheumatoid arthritis, Crohn's disease, ankylosing spondylitis, ulcerative colitis, and psoriatic arthritis), etanercept (approved in the U.S. for the treatment of rheumatoid arthritis, juvenile rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, and psoriasis), and adalimumab (approved for the treatment of rheumatoid arthritis and psoriatic arthritis). Objective: To review the current literature supporting alternative (and currently off-label) dermatologic uses of TNF-a antagonists. Methods: A MEDLINE search (1966-March 2005) was conducted using the keywords “infliximab,” “etanercept,” “adalimumab,” “TNF inhibitors,” and “off-label” to identify published reports of off-label dermatologic uses of TNF-a inhibitors. Results: Anti-TNF-a therapies have been reported in the following dermatologic diseases: sarcoidosis, hidradenitis suppuritiva, cicatricial pemphigoid, Behçet's disease, pyoderma gangrenosum, multicentric reticulohistiocytosis, apthous stomatitis, Sneddon-Wilkinson disease, SAPHO syndrome, pityriasis rubra pilaris, eosinophilic fasciitis, Panniculitis, Crohn's disease, necrobiosis lipoidica diabeticorum, dermatomyositis, and scleroderma. The vast majority of these reports are in the form of individual case reports and small case series. Only two published randomized controlled trials involving the off-label use of a TNF inhibitor were found. Conclusions: A growing number of published reports suggest that anti-TNF-a therapies may be effective in the treatment of numerous inflammatory skin diseases outside their currently approved indications.

Rapid response of IgA pemphigus of the subcorneal pustular dermatosis subtype to treatment with adalimumab and mycophenolate mofetil

To the Editor: An otherwise healthy 41-year-old man presented with recurring crops of pruritic, serpiginous, erythematous papules and plaques on his trunk and proximal extremities. The lesions began as papules, became vesicles, scaled, crusted, and resolved with post-inflammatory hyperpigmentation. Biopsy showed a subcorneal blister containing neutrophils with epidermal acanthosis and spongiosis (Figs 1 and 2). Direct immunofluorescence testing showed intercellular staining for IgA in the upper epidermis (Fig 1).

Case report: Subcorneal pustular dermatosis in a Sudanese patient

Subcorneal pustular dermatosis (SPD) is a rare, benign, relapsing pustular eruption of unknown etiology. It usually develops in elderly women. Herein we describe a 23-yearold Sudanese male diagnosed with SPD, based on clinical and histological findings. The presentation is unusual; pustules involving the whole body sparing palms, soles, axillae and groin. The patient recovered completely after 8 weeks treatment of 100mg/day oral dapsone. Sudanese Journal of Dermatology Vol. 3(2) 2005: 83-87

Early but not lasting improvement of recalcitrant subcorneal pustular dermatosis (Sneddon-Wilkinson disease) after infliximab therapy: relationships with variations in cytokine levels in suction blister fluids

Subcorneal pustular dermatosis (SCPD) is an uncommon disorder, characterized by a chronic relapsing vesiculopustular eruption, mainly involving the trunk and intertriginous areas, and usually seen in women > 40 years old. Various therapies have been reported to be effective in treating SCPD, such as dapsone, systemic glucocorticoids, acitretin, etretinate, infliximab and phototherapy. We report a case of a 54-year-old woman affected by SCPD who after failure of different therapies showed a dramatic but only temporary improvement of her disease during a cycle of therapy with infliximab. In addition, an array of cytokines was simultaneously measured in suction blister fluids obtained from involved or uninvolved skin at various time intervals during the first 12 weeks of observation.

Pustulocrustaceous Secondary Syphilis

Sir, A generalized pustular eruption in an adult may be the presenting feature of viral infections, drug eruptions, psoriasis, subcorneal pustular dermatosis or impetigo herpetiformis. Rarely, generalized pustulation is a manifestation of secondary syphilis. We present here a case of secondary syphilis with a dramatic generalized eruption of pustules followed by impetiginous lesions. The classification of pustular syphilis is also reviewed herein.

Atypical IgA/IgG Pemphigus Involving the Skin, Oral Mucosa, and Colon in a Child: A Novel Variant of IgA Pemphigus?

Immune-mediated blistering diseases are rare in childhood, with the subset of IgA pemphigus being extremely uncommon. A child with a bullous disorder of the oral mucosa, skin, and colon is reported because of the unusual nature of the clinical and laboratory findings. Immunofluorescence studies demonstrated both intercellular epidermal and basement membrane zone deposition of IgA and IgG antibodies, as well as intercellular colonic deposition of IgA antibodies. IgA and IgG ELISA tests were positive for desmoglein 3 as the intercellular epidermal antigen. The generation of multiple antibodies against several potential antigenic targets suggests epitope spreading may play a role in this disease. We believe this represents a novel variant of IgA pemphigus.

Diffuse Sterile Pustular Eruption with Changing Clinical Features in a 2‐Year Old

We report a 2-year-old girl with diffuse pustular eruptions occurring in close association with respiratory tract infections. The pustular eruption had different clinical characteristics over time, evolving from circinate to von Zumbush pustular psoriasis, and finally to subcorneal pustular dermatosis. Treatment with acitretin 1 mg/kg/day gave good results. A relapse showing striking clinical characteristics of subcorneal pustular dermatosis was treated with dapsone (1 mg/kg/day) followed by ultraviolet B-narrowband (UV-B-NB) phototherapy. The patient subsequently had several relapses over 1 year, which were well controlled with short cycles of UV-B-NB. This patient's findings demonstrate that pustular eruptions can vary over time, assuming clearly different clinical patterns, and highlight the difficulty of classifying pustular eruptions as separate diseases.

Multiple neutrophilic dermatoses occurring in a pediatric patient with glomerulonephritis

N eutrophilic dermatoses (ND) are characterized histologically by an epidermal and/ or dermal infiltrate of polymorphonuclear leukocytes, absence of microorganisms on special stains and cultures, and clinical improvement after treatment with systemic steroids. ND includes subcorneal pustular dermatosis, Sweet’s syndrome, erythema elevatum diutinum (EED), pyoderma gangrenosum (PG), neutrophilic eccrine hidradenitis, and granuloma faciale. We describe a pediatric patient with glomerulonephritis who successively developed 3 types of ND: EED-like dermatosis; subcorneal vesicular neutrophilic eruption; and acute form of PG.

Erfolgreiche Therapie des IgA-Pemphigus vom subkorneal pustul�sen Typ

IgA pemphigus is a rare autoimmune intraepidermal blistering disease characterized by in vivo bound, and circulating IgA autoantibodies that target cell surface components (cadherins) of epidermal keratinocytes. The average age of onset is approximately 50 years. Histological hallmarks of IgA pemphigus are epidermal acantholysis, subcorneal or intraepidermal pustulosis, and neutrophilic infiltration. The main clinical characteristics are erythematous skin lesions with vesiculopustules, erosions, crusts and desquamation, favoring the trunk, groins, auxiliaries, and proximal extremities. The drug of choice for treating IgA pemphigus is diaminodiphenylsulfone. In this case study, we describe a patient who suffered from IgA pemphigus and responded well to diaminodiphenylsulfone.

Autoimmune Bullous Diseases

The ocular manifestations of autoimmune bullous diseases are common and potentially sight-threatening. Major ophthalmic involvement is most commonly seen in mucous membrane pemphigoid (cicatricial pemphigoid), epidermolysis bullosa acquisita, linear IgA bullous disease, pemphigus vulgaris and paraneoplastic pemphigus. The main pathological process is related to autoimmune-induced conjunctival inflammation with consequent lid and corneal pathology, which may eventually result in permanent visual loss. Ocular involvement can be asymptomatic. Early detection is aided by careful attention to symptoms and signs of early ophthalmic disease. Ocular disease can be difficult to treat and management usually involves systemic therapy with immunomodulators to control inflammation and prevent progression to irreversible blindness, as well as surgical intervention in advanced disease. Recent advances in treatment, including methotrexate, mycophenolate mofetil, monoclonal antibodies and topical tacrolimus therapies, have led to promising results.

Subcorneal Pustular Dermatosis Associated with Palmo‐Plantar Pustular Psoriasis: Response to Colchicine Therapy

Subcorneal Pustular Dermatosis Associated with Palmo‐Plantar Pustular Psoriasis: Response to Colchicine Therapy

Case of multiple myeloma associated with extramedullary cutaneous plasmacytoma and pyoderma gangrenosum

A variety of cutaneous manifestations has been described in multiple myeloma including extramedullary cutaneous plasmacytomas, cutaneous amyloidosis, pyoderma gangrenosum, leukocytoclastic vasculitis, necrobiotic xanthogranuloma, scleromyxedema, Sweet's syndrome, subcorneal pustular dermatosis, scleredema, and plane xanthomas etc. An 89-year-old Korean man, who had been suffering from multiple myeloma 1 year previous, presented for evaluation of two nodules on the right side of the forehead, left side of the chest (7th rib area), and multiple ulcers with papulopustules on both the thigh and the left side of the chest (2nd rib area) during 15 days, which developed at the same time. A biopsy of a lesion which manifested as a cutaneous nodule on the right side of the forehead revealed dermal infiltration by well-differentiated plasma cells, similar to those found on a bone marrow biopsy, and a biopsy of the lesion manifested as a painful ulceration on the right thigh area showing dermal neutrophilic infiltration. Histologic findings were consistent with plasmacytoma and pyoderma gangrenosum, respectively. We present a case of multiple myeloma which developed extramedullary cutaneous plasmacytoma and pyoderma gangrenosum simultaneously, which is very rare. The patient was treated with a systemic steroid and conservative therapy.

Regression of subcorneal pustular dermatosis type of IgA pemphigus lesions with azithromycin

We present our experience with a 56-year-old man who complained for generalized dermatopathy, manifested by skin lesions with diameter from 0.5 to 5 cm. The lesions did not respond to a 20-day systemic steroid regimen. The results of biopsies of three excised lesions, in combination with the clinical manifestations, led to the diagnosis of subcorneal pustular dermatosis type of IgA pemphigus. An unexpected improvement was noted after treatment with azithromycin (which was provided for management of concurrent non-specific urethritis) and local non-potent steroid plus keratolytic agent ointment

FC‐19 Autoantibodies against extracellular domains of desmocollin 1 are not involved in canine pemphigus foliaceus

Pemphigus foliaceus (PF) is an autoimmune skin disease of dogs and humans. In human PF, the autoimmune target has been identified as desmoglein (Dsg) 1, a desmosomal cell–cell adhesion molecule, whereas the target in canine PF has not been identified. Many studies have suggested the possibility of Dsg1 being the target molecule. However, the pathological characteristics are similar to those of SPD type IgA pemphigus in humans, the target molecule of which is desmocollin (Dsc) 1. In this study, we attempted to clone canine Dsc1 and investigated whether canine PF sera could recognize Dsc1. Total RNA was purified from the muzzle skin of a healthy dog, and the cDNA of Dsc1 was amplified by RT‐PCR. Sequence analysis showed that the open reading frame of the extracellular domain of Dsc1 consisted of 695 amino acids and shared 82 and 79% amino acid identities with human and mouse Dsc1, respectively. The recombinant extracellular domain of Dsc1 was expressed by transient transfection with CHO cells. We used six canine PF sera: four sera that were positive in the indirect immunofluorescence test, two sera that were negative, and two normal canine sera. Immunoprecipitation‐immunoblotting analysis revealed that no canine PF sera or normal sera showed affinity for recombinant Dsc1. Although the tested sera were limited, the results suggest that no autoantibodies against the extracellular domain of Dsc1 were involved in the pathogenesis of canine PF and that another cell surface molecule may be involved. Funding: Self‐funded.

Les dermatoses neutrophiliques

Purpose. – The neutrophilic dermatoses are a group of skin diseases mainly characterized by an infiltration of the skin by normal polymorphonuclears, without any identifiable (infectious) cause. In this review we describe the main neutrophilic dermatoses and point on their multisystemic dimension. Current knowledge and key-points. – Well-defined neutrophilic dermatoses are Sweet's syndrome, pyoderma gangrenosum, subcorneal pustular dermatosis, erythema elevatum diutinum and neutrophilic eccrine hidradenitis, as well as newer and rarer conditions such as aseptic abscesses. Clinical overlap between these disorders led to the concept of “the” neutrophilic dermatosis. In addition, patients with a neutrophilic skin disorder may also suffer from extra-cutaneous aseptic neutrophilic infiltrates. This “neutrophilic disease” is often difficult to diagnose. Neutrophilic dermatoses are significantly associated with systemic disease. These include hematological disorders, inflammatory bowel disease, joint immunological disorders, and other malignant or inflammatory conditions. First-line treatment of acute neutrophilic conditions is steroid therapy. In chronic conditions, dapsone is often efficient. Future prospects and projects. – The mechanisms underlying the inappropriate activation of polymorphonuclears are poorly understood. Hematopoietic growth factors and adhesion molecules are believed to play a role in the pathophysiology of the neutrophilic dermatoses.

Subcorneal pustular dermatosis and Sjögren's syndrome

A 41‐year‐old Japanese woman presented at a local outpatient clinic because of a slightly pruritic pustular eruption on the trunk and extremities. Her skin lesion had been treated using an antifungal cream, but the condition had continued to worsen. According to the patient, the same pustular eruption had occurred during pregnancy, but diminished after delivery. She has no family history of skin eruption. On physical examination, she presented with well‐circumscribed erythematous macules with small pustules on the borders, involving the axilla, groin, upper and lower extremities and upper back (Fig. 1). Bacterial and fungal cultures of the lesions were negative. A skin biopsy obtained from a lesion in the left forearm demonstrated a subcorneal pustule containing polymorphonuclear leukocytes (Fig. 2). A perivascular dermal infiltrate was present, consisting predominantly of mononuclear cells. There was no spongiosis or acantholysis. On direct immunofluorescence, there were no immunoglobulin A (IgA) and complement 3 (C3) deposits in the intercellular space of the epidermis.Clinical appearance of the annular erythema with small pustules on the forearmimageSurgically excised specimen showing subcorneal pustules containing neutrophils and scattered eosinophils (hematoxylin and eosin; magnification ×200)imageThe clinical and histopathological findings were consistent with a diagnosis of subcorneal pustular dermatosis (SPD). Laboratory investigations showed hyper immunoglobulin A (IgA) immunoglobulinemia (479 mg/dL, normal, 110–410) and a high titer of antinuclear antigen (speckled type) at 1 : 160 (normal < 1 : 40) and anti‐single‐strand (anti‐ss) DNA‐IgG at 1 : 25 (normal : negative). Other findings were normal. Serum and urine immunoelectrophoresis showed no paraprotein bands. Administration of topical diflupredonate ointment and oral prednisolone improved but did not completely resolve the eruption. The patient was then treated with dapsone 75 mg daily, leading to reasonable control.Because speckled type antinuclear antibody and anti‐ss‐DNA antibody were positive in spite of the fact that autoantibodies anti‐Sjögren's syndrome (SS)‐A and SS‐B were negative, we asked the patient if she had experienced a dry sensation in her eyes and mouth. As she reported a dry sensation of both eyes and mouth, we referred her to the ophthalmology clinic. The Schilmer test was positive (2 mm of wetting per 5 min, with the patient unanesthetized). Rose Bengal dye and slit‐lamp examination revealed Sjögren's syndrome pattern. Lip biopsy revealed the accumulation of numerous lymphocytes in the salivary gland. Thus, our patient fulfilled four criteria of the European multicenter study,1 suggesting a diagnosis of definite Sjögren's syndrome.

The detection of IgG and IgA autoantibodies to desmocollins 1-3 by enzyme-linked immunosorbent assays using baculovirus-expressed proteins, in atypical pemphigus but not in typical pemphigus.

We have shown previously that human desmocollin (Dsc) 1 is recognized by IgA autoantibodies of subcorneal pustular dermatosis (SPD) type IgA pemphigus. However, the presence of IgG anti-Dsc autoantibodies is still controversial, and antibodies to Dsc2 and Dsc3 have not been clearly identified. To investigate this by producing recombinant proteins consisting of the entire extracellular domains of human Dsc1, 2 and 3 in baculovirus, and to use them to establish an enzyme-linked immunosorbent assay (ELISA). By this ELISA, we examined in total 165 cases of various types of autoimmune bullous diseases, as well as 23 normal controls. None of 45 sera of classical pemphigus showed either IgG or IgA antibodies to any Dsc. In contrast, one atypical pemphigus serum showed both IgG and IgA antibodies to Dsc1, which were adsorbed by incubation with Dsc1 baculoprotein. Furthermore, this ELISA detected both IgA and IgG anti-Dsc3 antibodies in one atypical case, and IgA antibodies to both Dsc2 and Dsc3 in another. This reactivity was confirmed by positive IgA immunofluorescence with Dsc2 and Dsc3 expressed on COS-7 cells. These results show that both IgG and IgA autoantibodies against all of Dsc1-3 are present in the sera of particular cases of nonclassical pemphigus, except for IgG antibodies to Dsc2, but that they are not detected in classical pemphigus. Unexpectedly, although IgA antibodies of all of eight SPD type IgA pemphigus sera reacted with Dsc1 expressed on COS-7 cells, only one serum was positive in Dsc1 ELISA for IgA. This result indicates either that Dscs expressed by baculovirus may not adopt the correct conformation or that Dscs may need association with other molecules to express all the epitopes for autoantibodies.

A Review of the Use of Infliximab to Manage Cutaneous Dermatoses

Infliximab is a chimeric monoclonal antibody that binds specifically to human tumor necrosis factor-alpha (TNF-alpha), decreasing the effect of the cytokine in inflammatory diseases. The aim of this study was to review the efficacy and safety of infliximab in the treatment of dermatological diseases. A MEDLINE search (1966-January 2003), using the keyword "infliximab" was performed to find relevant articles pertaining to the use of infliximab in dermatology. Infliximab has been used in the following dermatological diseases: psoriasis, Behcet's disease, graft versus host disease, hidradenitis suppurativa, panniculitis, pyoderma gangrenosum, SAPHO (synovitis, acne, pustulosis, hyperostosis and osteitis) syndrome, sarcoidosis, subcorneal pustular dermatosis, Sweet's syndrome, toxic epidermal necrolysis, and Wegener's granulomatosis. There is a generally good safety profile for infliximab, which is similar to that when it is used to treat Crohn's disease and rheumatoid arthritis. Although not approved for use in dermatological diseases, there have been numerous reports of the efficacy of infliximab in cutaneous inflammatory diseases. The most promise lies in those diseases that have increased amounts of TNF-alpha in the cutaneous lesions, such as psoriasis.