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Subcorneal pustular dermatosis

Subcorneal pustular dermatosis
Author:
Arianne Shadi Kourosh, MD
Section Editor:
Jeffrey Callen, MD, FACP, FAAD
Deputy Editor:
Abena O Ofori, MD
Literature review current through: Jul 2022. | This topic last updated: Apr 05, 2022.

INTRODUCTION — Subcorneal pustular dermatosis (SPD), also known as Sneddon-Wilkinson disease, is a rare neutrophilic dermatosis in which recurrent crops of sterile pustules appear in the most superficial (subcorneal) layers of the skin (picture 1A-B). The pustules are usually distributed in annular or serpiginous patterns and are most commonly located on flexural surfaces and on intertriginous skin. SPD is characterized by its clinical presentation, as its etiology is unknown and its nosology remains controversial.

In the overwhelming majority of cases, SPD is a chronic and benign condition for which the primary concerns are minimizing morbidity, improving quality of life, and ruling out the presence of an associated internal disease. Oral dapsone is the treatment of choice for SPD.

The clinical features, diagnosis, and management of SPD will be reviewed here. Other neutrophilic dermatoses and pustular disorders are reviewed separately. (See "Neutrophilic dermatoses" and "Approach to the patient with pustular skin lesions".)

EPIDEMIOLOGY — Since Sneddon and Wilkinson first described subcorneal pustular dermatosis (SPD) in the 1950s, the majority of cases have been reported in adult females, generally over the age of 40 [1,2]. SPD is considered a rare condition; however, no estimate of global incidence or prevalence is available.

There is no known ethnic or geographic predilection. SPD is observed worldwide [3,4]. The relatively few cases reported in children tend to be atypical, and some have subsequently been reclassified as forms of psoriasis [5].

PATHOGENESIS — The pathogenesis of subcorneal pustular dermatosis (SPD) is unknown. Cases identified have been distinguished by sterile collections of neutrophils and neutrophil-related cytokines (eg, interleukin [IL] 1-beta, IL-6, IL-8, IL-10, leukotriene B4, complement fragments [C5a], and tumor necrosis factor [TNF]-alpha) in the uppermost layers of the epidermis, in conjunction with consistently negative cultures [6-9]. While associated microbes are, by definition, never found in the skin, the question of possible infectious triggers elsewhere in the body has been debated, and other etiologic triggers or explanations for why this pustular reaction occurs in the subcorneal layer of the skin have not been demonstrated.

The clinical and histologic presentation of SPD, with annular arrangements of subcorneal sterile pustules, has led some clinicians to classify it as a form of pustular psoriasis (see 'Cutaneous manifestations' below). Meanwhile, the presence of cutaneous and circulating autoantibodies to components of the skin in a subset of patients has led others to consider it an overlap or subtype of pemphigus. Moreover, its coexistence at times with paraproteinemias and myeloma and its clustering with other neutrophilic dermatoses seen with these entities have suggested that SPD may be a cutaneous manifestation of hematologic dyscrasias or cancers (see 'Associated disorders' below). What may reconcile these various observations regarding SPD is to view the condition as a reaction pattern in the skin that may result from the convergence of various etiologies that induce a similar subcorneal neutrophilic process to manifest in the skin, and to consider the concept of subtypes.

The condition historically considered as Sneddon-Wilkinson disease, now considered by some as a "classical" subtype of SPD, has not been thought to be associated with autoantibodies. Patients with negative skin immunofluorescence and serum studies for autoantibodies have been reported [10].

The occasional identification of intraepidermal deposition of immunoglobulin G (IgG) and, more commonly, immunoglobulin A (IgA) antibodies to structural proteins of the skin on immunofluorescence studies performed on patients with clinical and histologic findings consistent with SPD has led some clinicians to reconsider the classification of SPD as a variant of the pemphigus family of autoimmune blistering diseases (ie, SPD-type IgA pemphigus) or to consider these cases a pemphigus subtype of SPD or variant of SPD [11,12]. In cases where antibodies to the skin are present, they target proteins called desmocollins, most commonly desmocollin 1; however, disease targeting desmocollins 2 and 3 also has been observed [13,14]. Desmocollins are members of the cadherin family of structural proteins necessary for cell-to-cell adhesion and are distinct from the desmoglein proteins targeted in pemphigus variants (eg, pemphigus vulgaris [desmoglein 3 and 1] and pemphigus foliaceous [desmoglein 1]). When these proteins are targeted, the structural framework linking skin cells together breaks down and vesicles or bullae are formed, the size and thickness of which depend on the level of the skin where the protein target occurs. As desmocollin 1 is found in the more superficial layers of the skin, the result of its loss of function would be small, superficial vesicles and pustules that desquamate into fine scale.

While SPD in many cases occurs as a chronic, benign process in individuals with no other identified internal disease, it has also been observed to cluster with the group of neutrophil-mediated dermatoses (eg, pyoderma gangrenosum and associated internal conditions) [15-22]. Some of these patients have been found to have underlying paraproteinemias (predominantly IgA monoclonal gammopathies), myeloma, cutaneous manifestations of hyperviscosity, or, rarely, lymphomas or solid tumors [23-30]. Gammopathies may play a role in pathogenesis, particularly given the association between IgA and neutrophilic reactions [31]. However, a clear mechanism has not been established, as immunofluorescence studies are negative in most patients with SPD, and not all patients with SPD have an associated gammopathy. (See 'Associated disorders' below.)

CUTANEOUS MANIFESTATIONS — Subcorneal pustular dermatosis (SPD) is typically a relapsing and remitting eruption of superficial pustules, predominating on the trunk and proximal extremities and favoring flexural and intertriginous regions (eg, axillae, groin, neck, and inframammary folds) (picture 1A-B). The face, palmar-plantar regions, and mucosae tend to be spared.

The pustules of SPD may arise within hours and can develop on normal or mildly erythematous skin. Although the pustules are generally a few millimeters in diameter, patients may also develop larger, flaccid bullae that contain sterile pus in the lower portion. These bullae are often called "half-half" blisters (picture 1B-C) [32]. The pustules group and coalesce into annular, circinate, or serpiginous configurations, then rupture or desquamate with superficial crust. Pustules often resolve with mild hyperpigmentation.

The eruption is often asymptomatic, although some patients experience pruritus or a sensation of skin irritation in involved areas. Classically, patients do not have systemic symptoms. If systemic symptoms are present, the clinician should consider an alternative diagnosis or an underlying systemic disease. (See 'Associated disorders' below.)

The course of SPD generally is chronic or recurrent. SPD may subside, resulting in remission, or persist for years. (See 'Prognosis' below.)

ASSOCIATED DISORDERS — In the majority of cases, subcorneal pustular dermatosis (SPD) occurs in isolation and is confined to the skin. However, SPD can be associated with other cutaneous and systemic conditions, such as Raynaud phenomenon, Sjögren syndrome, systemic lupus erythematosus (SLE), and neutrophilic dermatoses (eg, pyoderma gangrenosum, Sweet syndrome) [15,16,33-35]. There have also been reports of associations with internal diseases, including ulcerative colitis, Crohn disease, hyperthyroidism, hypothyroidism, rheumatoid arthritis, acute polyarthritis, SAPHO (synovitis, acne, pustulosis, hyperostosis, osteitis) syndrome, amicrobial lymph node suppuration, and aseptic spleen abscesses, as well as with hematologic disorders, such as polycythemia rubra vera and paraproteinemias (predominantly immunoglobulin A [IgA], either kappa or lambda light-chain type, and very rarely immunoglobulin M [IgM] and immunoglobulin G [IgG] gammopathies), cryoglobulinemia, and even with malignancies, such as myeloma, apudoma (amine precursor uptake and decarboxylation cell-derived tumor), and in very rare cases lymphomas and solid tumors (eg, thymoma) [17-31,36]. Conclusions on the strength of these disease associations are limited by the rarity of SPD.

HISTOPATHOLOGY — Subcorneal pustular dermatosis (SPD) is characterized by subcorneal vesicles or pustules composed of predominantly neutrophils with occasional eosinophils (picture 2). This finding is not specific for SPD. Impetigo, pustular psoriasis, acute generalized exanthematous pustulosis (AGEP), pemphigus foliaceus, and dermatophytosis may present with similar histologic features. Acantholysis may be present, but is not prominent, and typically is a secondary change seen in specimens from older lesions. (See 'Skin biopsy' below.)

DIAGNOSIS — The diagnosis of subcorneal pustular dermatosis (SPD) is based upon the recognition of consistent clinical and histologic findings and the exclusion of other disease entities. Findings that strongly support a diagnosis of SPD include:

Cutaneous eruption of superficial pustules in annular, circinate, or serpiginous configurations predominating on the trunk and proximal extremities and favoring flexural and intertriginous regions

Absence of drug exposure history suggestive of acute generalized exanthematous pustulosis (AGEP) (see "Acute generalized exanthematous pustulosis (AGEP)", section on 'Eliciting factors')

Absence of personal or family history of psoriasis

Absence of mucosal involvement

Absence of nail changes or joint findings associated with psoriasis or psoriatic arthritis (see "Psoriasis: Epidemiology, clinical manifestations, and diagnosis" and "Clinical manifestations and diagnosis of psoriatic arthritis")

Microscopic findings of subcorneal pustules in the absence of evidence for infection or histologic features that suggest other diagnoses (eg, spongiosis, acantholysis)

The likelihood of SPD is also strengthened if the patient is middle-aged and female. However, SPD can occur in other individuals. (See 'Epidemiology' above.)

There are no serologic tests that confirm a diagnosis of SPD.

Physical examination — A full skin examination should be performed in patients with suspected SPD to evaluate for physical signs suggestive of other conditions. The mucosa should not be involved, and nail changes or joint deformities consistent with psoriasis should be absent. The physical examination may also identify clinical signs suggestive of an associated systemic disease. (See 'Evaluation for associated disorders' below.)

Skin biopsy — Skin biopsy is important for confirming SPD and should be performed whenever feasible. Ideally, the specimen should include a relatively new, intact lesion. A 4 mm punch biopsy usually is sufficient. (See 'Histopathology' above.)

The key histologic finding in SPD is the subcorneal neutrophilic vesicle or pustule (picture 2). The absence or minimal presence of epidermal spongiosis in SPD aids in distinguishing SPD from pustular psoriasis, in which spongiosis is more apparent. The lack of pallor, edema, or necrosis in the epidermis and the absence of a psoriasiform pattern of hyperplasia help to distinguish SPD from necrolytic migratory erythema [37]. (See 'Differential diagnosis' below.)

Fungal stains (eg, periodic acid-Schiff) are useful to rule out fungal infection. Direct immunofluorescence studies should be performed to distinguish antibody-mediated subtype of SPD or variants of pemphigus (eg, immunoglobulin A [IgA] pemphigus or pemphigus foliaceous) as well as dermatitis herpetiformis. (See 'Pathogenesis' above.)

Direct immunofluorescence studies for epidermal intercellular IgA staining should be performed periodically in patients with relapsing disease. In some cases, positive direct immunofluorescence studies have developed years after the initial diagnosis of SPD. Thus, immunofluorescence studies may help to identify patients with IgA pemphigus subtypes of the condition.

Culture — A swab culture or tissue culture from punch biopsy should be performed to rule out infectious conditions such as impetigo.

EVALUATION FOR ASSOCIATED DISORDERS — The possibility of an associated disease should be considered in all patients with subcorneal pustular dermatosis (SPD). Often, a review of systems is useful for identifying symptoms suggestive of extracutaneous associations. In particular, patients should be asked about symptoms associated with rheumatologic, hematologic, or inflammatory bowel disease:

Arthralgia

Raynaud phenomenon

Dry eyes or dry mouth (suggestive of Sjögren syndrome)

Gastrointestinal symptoms (suggestive of inflammatory bowel disease)

History of livedoid appearance of the arms and legs or bluish discoloration of the fingers and toes (suggestive of hyperviscosity of the blood)

A thorough physical examination may also identify signs suggestive of underlying disease.

Laboratory workup can be useful for identifying disorders that may occur in association with SPD. Routine tests to perform on all patients are:

Complete blood count with differential – Evaluates for polycythemia, neutropenia, or lymphopenia seen with rheumatologic conditions that may occur in association with SPD (see 'Associated disorders' above)

Serum protein electrophoresis and immunofixation – Evaluates for monoclonal gammopathy

When positive in patients with SPD, serum protein electrophoresis usually reveals the presence of immunoglobulin A (IgA) paraproteins. Both kappa and lambda light-chains may be seen. Immunoglobulin G (IgG) and immunoglobulin M (IgM) monoclonal gammopathies are rare. Serum protein electrophoresis should be repeated periodically while the patient has active skin disease (eg, once yearly) because paraproteinemia can develop years after the initial presentation of SPD and because of the risk of progression of paraproteinemia to multiple myeloma. If myeloma is suspected, further evaluation is indicated. (See "Multiple myeloma: Clinical features, laboratory manifestations, and diagnosis", section on 'Diagnosis'.)

In addition, the review of systems may lead to suspicion for underlying rheumatologic diseases that require further laboratory workup, such as Sjögren syndrome, systemic lupus erythematosus (SLE), rheumatoid arthritis, and cryoglobulinemia.

DIFFERENTIAL DIAGNOSIS — The differential diagnosis of subcorneal pustular dermatosis (SPD) includes other disorders that may present with widespread pustules or annular, circinate, or serpiginous plaques. Examples include pustular psoriasis, acute generalized exanthematous pustulosis (AGEP), impetigo, dermatophytosis, eosinophilic pustular folliculitis, dermatitis herpetiformis, necrolytic migratory erythema (NME), pemphigus foliaceus, and immunoglobulin A (IgA) pemphigus. Pustular psoriasis is probably the most difficult entity to distinguish from SPD. Many cases initially diagnosed as SPD subsequently have been found to be pustular psoriasis (see 'Pathogenesis' above):

Generalized pustular psoriasis – Generalized pustular psoriasis (GPP) is an uncommon presentation of psoriasis characterized by the acute or subacute development of a widespread pustular eruption. In acute GPP (picture 3), the pustules are accompanied by extensive erythema and systemic symptoms (eg, fever, malaise). Generalized annular pustular psoriasis is a subacute presentation that manifests with widespread annular or figurate plaques with pustules. GPP should be suspected in a patient with a patient or family history of psoriasis or nail or joint findings of psoriasis. GPP may also occur as a disorder of pregnancy (impetigo herpetiformis). Like SPD, subcorneal pustules are found in biopsy specimens of GPP. However, epidermal spongiosis is more consistent with GPP. (See "Pustular psoriasis: Pathogenesis, clinical manifestations, and diagnosis", section on 'Generalized pustular psoriasis'.)

Acute generalized exanthematous pustulosis – While both SPD and acute generalized exanthematous pustulosis (AGEP) present with the rapid onset of cutaneous pustulosis, AGEP is accompanied by fever and peripheral blood leukocytosis (picture 4). Additional findings include eosinophilia, facial edema, atypical lymphocytes, and elevated liver function tests [38]. A thorough drug exposure history must be taken to distinguish AGEP and SPD. (See "Acute generalized exanthematous pustulosis (AGEP)".)

Impetigo – Impetigo, a cutaneous bacterial infection caused by Staphylococcus aureus or beta-hemolytic streptococci, may present as a localized or widespread eruption consisting of pustules that rapidly evolve into adherent golden crusts (nonbullous impetigo) or flaccid bullae with clear or turbid fluid (bullous impetigo) (picture 5A-B). Swab culture for bacteria or a tissue biopsy will identify the causative bacteria. Impetigo is most common in children. (See "Impetigo".)

Dermatophytosis – Tinea corporis and tinea cruris most commonly present as scaly, erythematous patches or plaques on the skin, often with annular or serpiginous borders. Occasionally, pustules are also present (picture 6). A potassium hydroxide (KOH) preparation can quickly diagnose dermatophytosis. Alternative methods include fungal culture and skin biopsy with fungal stains (eg, periodic acid-Schiff stain). (See "Dermatophyte (tinea) infections" and "Office-based dermatologic diagnostic procedures", section on 'Potassium hydroxide preparation'.)

Eosinophilic pustular folliculitis – Eosinophilic pustular folliculitis is an uncommon disorder that usually presents with chronic, recurrent crops of sterile pustules in a seborrheic distribution (ie, face, upper trunk). In contrast to SPD, histopathologic examination of pustules reveals eosinophil-predominant infiltrates rather than neutrophil-predominant infiltrates. Leukocytosis or eosinophilia may also be present. Some cases are associated with HIV infection. (See "HIV-associated eosinophilic folliculitis".)

Dermatitis herpetiformis – Dermatitis herpetiformis usually presents with rapid onset of crops of papulopustules or vesicles (picture 7). Involved skin is markedly pruritic, unlike SPD. The classic distribution involves the back, buttocks, and extensor surfaces (especially over extensor aspects of joints), in contrast to the flexural and intertriginous distribution of SPD. Histopathologic examination reveals neutrophil collections and blister formation within the dermal papilla, in contrast to the subcorneal neutrophil collections in SPD. (See "Dermatitis herpetiformis".)

Necrolytic migratory erythema – Necrolytic migratory erythema (NME) is a cutaneous manifestation of glucagonoma or of certain nutritional deficiencies. Unlike SPD, NME is not characterized by pustules. Rather, it presents as a nonspecific dermatitis with erythematous patches, blisters, and erosions (picture 8) [37]. In NME, there is a predilection for sites of pressure and friction, such as the buttocks, groin, lower abdomen, and lower extremities, as well as mucosal regions (oral mucosa, lips, genital region) [37,39]. In SPD, mucosa should be spared. Associated symptoms include unexplained weight loss, diabetes, diarrhea, and stomatitis. On pathology, pallor, edema, and necrobiosis of the upper epidermis are suggestive of NME [37,40]. (See "Glucagonoma and the glucagonoma syndrome" and "Cutaneous manifestations of internal malignancy", section on 'Necrolytic migratory erythema'.)

Pemphigus foliaceus – Pemphigus foliaceus is an autoimmune blistering disease characterized by the development of superficial blisters that rapidly evolve into scaly, crusted erosions (picture 9). The scalp, face, and trunk are common sites of involvement. Unlike SPD, the subcorneal blisters of pemphigus foliaceus tend to be larger, and neutrophil predominance is not characteristic. Acantholysis is a prominent feature of pemphigus foliaceus but a less prominent feature in SPD. Direct immunofluorescence studies can confirm a diagnosis of pemphigus foliaceus. (See "Pathogenesis, clinical manifestations, and diagnosis of pemphigus".)

Although IgA pemphigus may be included in the differential diagnosis of SPD, overlap in the clinical and histologic features of SPD and IgA pemphigus have contributed to uncertainty about the classification of these conditions. Both disorders exhibit pustular eruptions in annular or circinate patterns that favor the trunk and proximal extremities and neutrophil-predominant subcorneal vesicles or pustules. It is controversial whether patients in whom clinical and histologic features of SPD are associated with the detection of antibodies against desmocollins are best classified as having a specific subtype of SPD or an SPD-like subtype of IgA pemphigus. (See 'Pathogenesis' above and "Pathogenesis, clinical manifestations, and diagnosis of pemphigus", section on 'IgA pemphigus'.)

TREATMENT — Oral dapsone is the mainstay of therapy for subcorneal pustular dermatosis (SPD). Patients who fail to respond to dapsone or cannot tolerate dapsone may be treated with phototherapy or other interventions. Given that the cutaneous manifestations of SPD are not life threatening, it is important to consider the risk-benefit ratio when selecting a therapeutic regimen.

In some cases, treatment of an associated underlying disease may result in improvement in SPD. As an example, treatment with an antimyeloma regimen (melphalan and autologous bone transplantation) was associated with a sustained remission of SPD in a patient who received this treatment following the progression of concurrent immunoglobulin A monoclonal gammopathy of undetermined significance to multiple myeloma [41].

No treatment has been found that can definitively cure the disease.

First-line therapy — The first-line therapy and treatment of choice for SPD is oral dapsone.

Oral dapsone — No randomized trials have evaluated the efficacy of dapsone for SPD. Use of this agent is based upon clinical experience that suggests the treatment is effective and generally well tolerated [7].

Typical adult doses for dapsone range from 50 to 200 mg per day. Hemolysis, hemolytic anemia, and methemoglobinemia are potential dose-related side effects. Hemolysis occurs to some degree in all patients treated with dapsone but may be particularly severe in patients with glucose-6-phosphate dehydrogenase (G6PD) deficiency. Testing for G6PD deficiency is recommended prior to beginning dapsone therapy. (See "Diagnosis and management of glucose-6-phosphate dehydrogenase (G6PD) deficiency".)

To minimize risk for hemolysis, it is beneficial to start at the relatively low dose of 25 to 50 mg per day and increase to therapeutic dose gradually (eg, by 25 mg per week) with laboratory monitoring to assess hematologic tolerance. Patients should be maintained at the lowest possible dose to control the disease. Resolution of cutaneous manifestations often occurs within four weeks [7]. Long-term treatment is usually necessary to maintain remission.

Rare serious hematologic side effects include agranulocytosis and aplastic anemia [42,43]. Other, relatively more common side effects are toxic hepatitis, nausea, headache, and cutaneous eruptions; insomnia, psychosis, sensory or motor peripheral neuropathy, and hypersensitivity reactions are additional side effects [44,45]. A complete blood count, liver function tests, and review of systems should be monitored periodically during dapsone therapy.

Second-line therapies — Second-line therapies for SPD may be administered when patients fail to respond well to first-line therapy or have contraindications to the use of dapsone therapy. Data on these treatments are limited to case reports, precluding definitive conclusions on optimal treatment regimens.

Phototherapy — Case reports document improvement in SPD after treatment with psoralen plus ultraviolet A (PUVA) [46], narrowband ultraviolet B (UVB) [47,48], broadband UVB [49], and PUVA in combination with retinoid therapy [48] or dapsone [50]. Phototherapy is typically administered two to three times per week at the start of treatment. The frequency of treatment is tapered after remission. Potential adverse effects include erythema, blistering, skin aging, and increased risk for cutaneous malignancy. Adverse effects of phototherapy are reviewed in greater detail separately. (See "UVB therapy (broadband and narrowband)", section on 'Short- and long-term adverse effects' and "Psoralen plus ultraviolet A (PUVA) photochemotherapy", section on 'Adverse effects'.)

Systemic glucocorticoids — Systemic glucocorticoids may control flares of SPD in patients with refractory disease [51]. Prednisone may be given at a dose of 0.5 to 1 mg/kg per day until a satisfactory therapeutic effect is achieved and tapered to the lowest dose possible to maintain treatment response. Long-term treatment with systemic glucocorticoids should be avoided when feasible because of the potential for serious side effects. The adverse effects of systemic glucocorticoid therapy are reviewed separately. (See "Major side effects of systemic glucocorticoids".)

Other therapies — A variety of additional interventions have been reported beneficial in small numbers of patients.

Topical agents — The relative safety of many topical therapies makes them attractive therapies for skin disease. Topical corticosteroids may be helpful for reducing cutaneous symptoms and signs of SPD and are an option for the treatment of patients with limited skin involvement or as an adjunct to systemic therapy [26,52,53]. The best regimen is unclear. For involved areas on the trunk or extremities, twice-daily application of a potent topical corticosteroid is reasonable, with lower-potency agents used for facial or intertriginous areas to minimize the risk for corticosteroid-induced skin atrophy. The frequency of application may be tapered as tolerated during maintenance therapy. (See "Topical corticosteroids: Use and adverse effects", section on 'Adverse effects'.)

Additional therapies postulated to be of benefit for SPD are topical tacalcitol, topical maxacalcitol, and topical dapsone. Treatment with topical tacalcitol (1-alpha-24R-dihydroxyvitamin D3) or topical maxacalcitol (22-oxacalcitriol) has been associated with improvement in SPD in case reports [54,55]. Topical crushed dapsone has been effective for pyoderma gangrenosum, suggesting a potential benefit for SPD and other neutrophilic dermatoses [56]. Further study is needed prior to a recommendation for the routine use of these therapies for SPD.

Systemic agents — Case reports suggest that some patients who cannot be managed with first- or second-line therapies can benefit from acitretin [57,58], pentoxifylline [59], colchicine [60], combination therapy with cyclosporine and prednisone [61,62], or biologic agents (eg, infliximab [8,63,64], etanercept [65,66], adalimumab [67,68], or guselkumab [69]). In addition, a case report describes marked improvement in recalcitrant disease with a combination of mycophenolate mofetil and adalimumab [70]. The risks of these treatments should be carefully considered prior to the initiation of therapy.

Other treatments that have appeared beneficial in case reports include oral nicotinamide [71] and antibiotics, such as doxycycline [72], trimethoprim-sulfamethoxazole [73], and azithromycin [74].

PROGNOSIS — Given that subcorneal pustular dermatosis (SPD) is a rare condition, follow-up data on treated patients are limited. However, SPD appears to be a cyclic and relapsing disease. Untreated patients may suffer attacks lasting days to several weeks and may experience recurrences over many years. While long-term or permanent remission is possible, this cannot be expected or predicted, and there is no definitive cure for the disease.

Despite the fact that SPD can cause morbidity directly related to skin disease (eg, pruritus, secondary infection, hyperpigmentation), when confined to the skin, the patient's general health generally is not compromised. However, patients with associated systemic disorders may experience related morbidity and mortality. (See 'Associated disorders' above.)

SUMMARY AND RECOMMENDATIONS

Overview – Subcorneal pustular dermatosis (SPD) is a rare disease characterized by recurrent eruptions of grouped, superficial pustules that favor flexural surfaces and skin folds. SPD most commonly affects middle-aged females. (See 'Epidemiology' above.)

Clinical manifestations – The pustules in SPD are usually a few millimeters in diameter and are often arranged in annular, circinate, or serpiginous configurations (picture 1A). Patients may also develop larger, flaccid bullae that contain sterile pus ("half-half" blisters (picture 1C)). (See 'Cutaneous manifestations' above.)

Associated disorders – SPD can be associated with internal conditions that can cause significant morbidity and mortality. Examples include paraproteinemias, hematologic cancers, solid tumors, inflammatory bowel disease, and rheumatologic disease. Patients with SPD should be evaluated and treated for associated diseases. (See 'Associated disorders' above and 'Evaluation for associated disorders' above.)

Diagnosis – Other dermatologic conditions can appear similar to SPD. The patient history, physical examination, skin biopsy, and cultures usually enable clinicians to distinguish SPD from other diseases. (See 'Differential diagnosis' above.)

Management – For patients with SPD, we suggest oral dapsone as first-line treatment (Grade 2C). (See 'Treatment' above.)

Prognosis – Sustained remission of SPD is possible; however, SPD is generally a chronic and relapsing condition. (See 'Prognosis' above.)

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Topic 99482 Version 9.0

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