Pustulose subcorneal L13.1

Rare, chronic, recurrent disease with formation of strictly subcorneal, sterile pustules.

The etiopathogenesis of this chronic pustulosis is unknown and its nosological classification remains controversial. No evidence of pathogens in the pustules. The migration of neutrophils through the epidermis indicates the presence of chemotactic factors in the upper epidermis. Tumor necrosis factor (TNF)-alpha, interleukin-8, C5a complement and IgA were detected in the subcorneal vesicles. An increase in interleukin-1b was detected in the eruption phase of the pustule. Interleukin-1b is an activator of TNF-alpha, suggesting that it may play a role in the pathogenesis of SPD. The role of TNF-alpha in the pathogenesis of the disease is supported by the response of the disease to TNF-alpha blockers such as adalimumab, and it has been suggested that neutrophil priming is a consequence of excessive production of TNF-alpha by keratinocytes. Serum levels of CCL17 (C-C motif chemokine ligand 17) are elevated, suggesting a Th2 response (Bhargava S et al. 2020).

There are associations with connective tissue diseases, thyroid diseases, medications and infections. The disease has been associated with neutrophilic dermatoses, including pyoderma gangrenosum and inflammatory bowel disease (i.e. Crohn's disease and ulcerative colitis).

Hematologic disorders: Numerous hematologic disorders, including aplastic anemia, lymphoma, multiple myeloma, chronic lymphocytic leukemia, IgG cryoglobulinemia, and monoclonal gammopathies, particularly IgA myeloma, have been associated with subcorneal pustulosis and may occur years after its onset. Therefore, screening for paraproteinemia is required to rule out myeloma. Regular screening is also recommended for patients who initially test negative. Malignancies of solid organs that have been reported include metastatic thymoma, apudoma and epidermoid carcinoma of the lung (Bhargava S et al. 2020). Associations with Sjögren's syndrome and systemic lupus erythematosus have also been reported.

Drugs: There have been reports of drugs that can cause reactions with PS-like features. This concerns multikinase inhibitors sorafenib and gefitinib. Furthermore, paclitaxel, isoniazid, amoxicillin, cefazolin sodium. The occurrence of subcorneal pustules due to dapsone and adalimumab has been reported as a therapeutic paradox.

Infections: Subcorneal pustulosis can be aggravated by various infections. Subcorneal pustulosis can be exacerbated by various infections, especially Mycoplasma pnemoniae infection, primary pulmonary coccidioidomycosis and urinary tract infections. Remarkably, the occurrence of pustules after echocardiography has been reported to develop 10 to 12 hours after the procedure (Ingber et al., 1983).

Occurs more frequently from the age of 50.

Women are affected 4 times more frequently than men (?).

Less common in children.

Mainly trunk and extremities, especially intertriginous areas are affected. The soles of the feet and palms, head and mucous membranes remain free.

Symmetrically arranged, grouped, also anularly arranged, initially firm, as they grow larger, flaccid, "hypopyon-like" pustules, which are surrounded by a narrow inflammatory border. As the surface of the pustules is very easily damaged, they burst prematurely.

Confluence and transformation lead to the formation of circinate or polycyclic, weeping and crusty areas with collerette-like blister cover remnants.

The healing pattern with extensive erythema surrounded by a raised scaly ridge is also characteristic. The exanthema eruptions often have a craniocaudal course.

In fresh pustular eruptions, considerable feeling of illness, accompanied by a steep rise in temperature. Neutrophilic leukocytosis is always detectable.

Elevation of ESR and CRP.

Mostly pronounced neutrophilic leukocytosis.

Pustular smear: Numerous neutrophils, rarely eosinophils.

Serum protein electrophoresis: Paraproteinemia in up to 40% of cases. Frequent monoclonal IgA gammopathy or IgG gammopathy.

Dermatitis herpetiformis: Immunohistologic differentiation possible by detection of granular IgA deposits.

Impetigo contagiosa: Bacteriologic examination

Bullous pemphigoid: Immunohistologic differentiation possible by detection of immunoglobulin deposits on the dermo-epidermal basement membrane.

Pemphigus vulgaris: Immunohistologic differentiation by detection of immunoglobulin deposits

Pemphigus foliaceus: (minus) variant of pemphigus vulgaris with high intraepidermal (subcorneal) continuity separation and thus very thin, volatile, easily tearing blister cover. In contrast to pemphigus vulgaris, mucosal changes are always absent in pemphigus foliaceus.

Pemphigus erythematosus: Detection of IgG antibodies in the intercellular substance and on the basement membrane, up to 60% positive lupus band test.

IgA pemphigus: IgA-AK: Positive immunofluorescence on the keratinocyte surface.

Genetic syndromes characterized by pustule formation, such as pyogenic arthritis/pyoderma gangrenosum/acne(PAPA syndrome) and SAPHO syndrome.

Pustular psoriasis: Some authors suggest that subcorneal pustulosis is closely related to pustular psoriasis. However, typical histopathologic features of pustular psoriasis, such as psoriasiform hyperplasia, parakeratosis and spongiform pustules, are not found in subcorneal pustulosis.

AGEP: Acute generalized exanthematous pustulosis: AGEP is a sudden, self-limited eruption typically triggered by a drug or infection. The presence of systemic symptoms, eosinophilia, marked edema of the papillary dermis, keratinocyte necrosis, mixed neutrophil-rich interstitial and mid-dermal infiltrates with eosinophils in the pustules or dermis distinguishes AGEP from Sneddon-Wilkinson type subcorneal pustulosis.

DADPS (e.g., dapsone-fatol) 100-150 mg/day, but only morbostatic effect can be achieved. Trial aromatic retinoids such as acitretin (Neotigasone) 0.5-1.0 mg/kg bw/day or isotretinoin (e.g., isotretinoin-ratiopharm; Acnenormin) 20-40 mg/day.

For refractory cases, consider methotrexate therapy(e.g., MTX) 5-15 mg/week.

Alternatively, a trial of fumaric acid esters (Fumaderm) may be undertaken.

Alternative: In single cases, the TNF-alpha inhibitors infliximab and etanercept have been successful.

Alternative: In other individual cases, therapeutic success with ciclosporin A, mycophenolate mofetil, adalimumab has been reported.

The entity of this clinical picture is increasingly being questioned.

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