Prurigo Nodularis Is Characterized by Systemic and Cutaneous T Helper 22 Immune Polarization.

Prurigo nodularis (PN) is an understudied, chronic inflammatory skin disease that disproportionately affects African Americans and presents with intensely pruritic nodules of unknown etiology. To better characterize the immune dysregulation in PN, PBMCs and skin biopsies were obtained from patients with PN and healthy subjects (majority African American) matched by age, race, and sex. Flow cytometric analysis of functional T-cell response comparing patients with PN with healthy subjects identified increased γδT cells (CD3+CD4-CD8-γδTCR+) and Vδ2+ γδT enrichment. Activated T cells demonstrated uniquely increased IL-22 cytokine expression in patients with PN compared with healthy controls. CD4+ and CD8+ T cells were identified as the source of increased circulating IL-22. Consistent with these findings, RNA sequencing of lesional PN skin compared with nonlesional PN skin and biopsy site‒matched control skin demonstrated robust upregulation of T helper (Th) 22‒related genes and signaling networks implicated in impaired epidermal differentiation. Th22‒related cytokine upregulation remained significant, with stratifications by race and biopsy site. Importantly, the expression of the IL-22 receptors IL22RA1 and IL22RA2 was significantly elevated in lesional PN skin. These results indicate that both systemic and cutaneous immune responses in patients with PN are skewed toward a Th22/IL-22 profile. PN may benefit from immunomodulatory therapies directed at Th22‒mediated inflammation.

Prurigo nodularis: Epidemiology and clinical features.

Prurigo nodularis (PN) is a chronic inflammatory skin disease characterized by intensely pruritic, hyperkeratotic nodules that favor the extensor surfaces of the extremities and the trunk. In addition to its significant impact on quality of life, many patients with PN are recalcitrant to therapy because there are currently no therapies approved by the US Food and Drug Administration. In the first article of this 2-part continuing medical education series, we describe the broader epidemiology, patient demographics, physical examination findings, and symptoms to aid in the timely recognition and diagnosis of PN. Furthermore, we quantify the burden of comorbidities in PN by discussing the broad spectrum of systemic diseases and mental health conditions that have been associated with this condition. The second article of this 2-part series focuses on the pathogenesis of PN and provides detailed algorithms for comprehensive work-up and management.

Eosinophilic dermatoses.

Eosinophilic dermatoses are a heterogeneous group of diseases, characterized by an eosinophil-rich infiltrate and/or degranulation of eosinophils. Blood eosinophilia may be an associated feature. Typical, albeit not specific histological findings include 'flame figures', which are caused by the accumulation of cationic proteins released by eosinophils and subsequent collagen denaturation. "Classic" eosinophilic dermatoses include eosinophilic cellulitis (Wells syndrome), granuloma faciale, eosinophilic fasciitis (Shulman syndrome) and eosinophilic folliculitis (Ofuji disease). In addition, there is a multitude of skin diseases that present with varying degrees of eosinophilic infiltration. These include atopic dermatitis, bullous pemphigoid, urticaria, allergic contact dermatitis, prurigo nodularis, arthropod bite reaction, parasitic infections, and drug hypersensitivity. Even though these disorders share a common characteristic (tissue eosinophilia), they differ greatly in their clinical presentation.

Aprepitant in Anti-histamine-refractory Chronic Nodular Prurigo: A Multicentre, Randomized, Double-blind, Placebo-controlled, Cross-over, Phase-II trial (APREPRU).

The aim of this multicentre, randomized, double-blind, placebo-controlled, cross-over, phase-II study was to determine the antipruritic effect of aprepitant vs. placebo in 58 patients with anti-histamine-refractory chronic pruritus in chronic nodular prurigo. Patients were randomized to receive either first oral aprepitant 80 mg/day or placebo for 4 weeks. Following a 2-week wash-out phase, the patients were crossed-over to receive the other treatment for 4 weeks. Primary efficacy criterion was the intra-individual difference between mean itch intensity (visual analogue scale) at baseline compared with the end of treatment period. Prurigo lesions, pruritus course, quality of life, patient benefits, and safety were secondary parameters. No significant differences were found between aprepitant treatment and placebo for any of the parameters investigated. Under the experimental conditions of the study, aprepitant, 80 mg daily for 4 weeks, did not have an antipruritic effect in patients with chronic prurigo. (DRKS00005594; EudraCT Number: 2013-001601-85).

[Epidemiological and clinical aspects of prurigo in HIV infected patients in Fousseyni N'Daou hospital of Kayes, Mali]. / Aspects Epidemiologiques et Cliniques du Prurigo Chez les Personnes Vivant avec le VIH a L'Hopital Fousseyni N'Daou de Kayes, Mali.

INTRODUCTION: Prurigo is one of the most common dermatological conditions during HIV infection and AIDS. It appears as an immunosuppression marker associated with HIV infection. The study objective was to determine the prevalence of prurigo in people living with the human immunodeficiency virus (PLHIV) in Fousseyni N'Daou Hospital of Kayes, and to describe the socio-demographic aspects of patients and lesions associated with prurigo among PLHIV. METHODS: It was a descriptive cross-sectional study included all cases of HIV infected patients with prurigo in the Dermatology-Venomology Department of Fousseyni N'DAOU Hospital from January 1, 2015 to August 31, 2015. RESULTS: We collected 121 cases of prurigo. The hospital prevalence was 14.5% among PLHIV with 65% Female and the average age was 34.8 years old (SD: 15-81 years). The elementary lesions associated with prurigo were seropapules (40.2%), vesiculo-crusts (13%), excoriated papules (33.3%), lichenified papules (10.8%), and cicatricial lesions (2.7%). The prurigo was generalized in 68.5% of cases and localized in 31.24%. More than half of our patients had weight loss, fever, diarrhea and oral candidiasis in their medical history. Patients were infected with HIV1 in 60.03% and HIV1+ 2 in 24.3%. More than the half of our patients had a CD4 count inferior to 250 cells/mm3 at the time of prurigo diagnosis. CONCLUSION: In our study, prurigo remains a common condition in PLHIV, particularly in patients with low CD4 counts. Early detection and rapid antietroviral therapy can reduce the frequency of prurigo in PLHIV.

INTRODUCTION: Le prurigo est l'une des affections dermatologiques les plus fréquentes au cours de l'infection à VIH et du sida. Il apparait comme un marqueur de l'immunodépression associée à l'infection VIH. L'objectif était de déterminer la prévalence du prurigo chez les personnes vivant avec le virus de l'immunodéficience humaine (PVVIH) à l'hôpital Fousseyni N'Daou de Kayes (HFDK) et décrire le profil sociodémographique des patients et les lésions associées au prurigo chez les PVVIH à HFDK. PATIENTS ET MÉTHODES: Il s'agissait d'une étude transversale descriptive de tous les cas de prurigo chez les PVVIH dans le service de Dermatologie-Vénéréologie de l'hôpital Fousseyni N'DAOU durant la période du 1er janvier 2015 au 31 août 2015. RÉSULTATS: Nous avons colligé 121 cas de prurigo. La prévalence hospitalière a été de 14,5% chez les PVVIH. Le sexe féminin a représenté 65% des cas. L'âge moyen a été de 34,8 ans (extrêmes :15 ­ 81 ans). Les lésions élémentaires associées au prurigo ont été les séropapules (40,2%), vésiculo-croutes (13%), papules excoriés (33,3%), papules lichenifiés (10,8%), lésions cicatricielles (2,7%). La forme généralisée a représenté 68,5% et la forme localisée 31,24%. Plus de la moitié de nos patients avait la notion d'amaigrissement, de fièvre, de diarrhée et des candidoses buccales dans leurs antécédents. Le VIH1 a représenté 60,03% et l'association VIH1 et VIH2 a représenté 24,3% des cas. Plus de la moitié de nos patients avait un taux de CD4 inférieure à 250 cellules/mm3 au moment du diagnostic du prurigo. CONCLUSION: Dans notre étude, le prurigo reste une affection fréquente chez les PVVIH, particulièrement lorsque le taux de CD4 est bas. Un dépistage précoce et le traitement antirétroviral rapide permet de réduire la fréquence du prurigo chez les PVVIH.

Invasive dermatophyte infection with Trichophyton interdigitale is associated with prurigo-induced pseudoperforation and a signal transducer and activator of transcription 3 mutation.

Invasive dermatophyte infection, with extension beyond the dermis, in immunocompetent hosts is exceptionally rare. Dermatophytes are keratinophilic and are usually confined to the stratum corneum, hair and nails. Susceptibility to dermatophyte infections is incompletely understood, but inherited mutations in key signalling pathways of the innate immune system have been identified. We report the first case of an invasive dermatophyte infection associated with abrupt onset of a prurigo-induced pseudoperforation and a loss-of-function mutation in signal transducer and activator of transcription 3 (STAT3).

There is no functional small-fibre neuropathy in prurigo nodularis despite neuroanatomical alterations.

Prurigo nodularis (PN) is a pruritic condition with altered epidermal neuroanatomy as demonstrated previously. Here we elucidated neuroimmunological mechanisms by combining functional, morphological and gene expression experiments in twelve subjects with PN and eight healthy controls. Subjects with PN showed a reduced intra-epidermal nerve fibre density (IENFD) in lesional skin. Quantitative sensory testing indicated maintenance of somatosensory function compared to controls. None of the tested molecular markers including the neuron-distracting SEMA3A and neuron-attracting NGF were altered in lesional vs non-lesional skin in PN subjects. Accordingly, we speculate that scratching may contribute to reduced IENFD rather than an authentic endogenous neuropathy.

Immunoglobulin G4-related disease presenting with prurigo: Circulating T-helper 2 cells may be involved in the pathogenesis.

We report a case of immunoglobulin G4-related disease (IgG4-RD) which presented with prurigo on the trunk and extremities. A 66-year-old man had a 2-month history of itchy erythematous papules on his trunk and extremities. Bilateral eyelid swelling and enlargement of the submandibular and parotid glands were also observed. Computed tomography revealed pleural thickening and diffuse pancreatic enlargement. Serum levels of IgG4 were markedly increased. A biopsy specimen obtained from an erythematous papule showed a perivascular inflammatory infiltrate of lymphocytes with eosinophils in the dermis, whereas a parotid gland biopsy revealed an infiltrate of abundant IgG4-positive plasma cells. Treatment with prednisolone resulted in improvement of the skin and other lesions along with a decrease in IgG4 serum levels. A flow cytometric assay revealed that percentages of interleukin (IL)-4- and IL-13-producing CD4(+) T cells were markedly higher in the circulation of the IgG4-RD patient than in that of healthy subjects. Moreover, those populations dramatically decreased after treatment. Thus, prurigo may be a skin manifestation of IgG4-RD and T-helper 2 cells may contribute to the pathogenesis.

Protective Role of STAT6 in Basophil-Dependent Prurigo-like Allergic Skin Inflammation.

Prurigo is a common, but treatment-resistant, skin disease characterized by persistent papules/nodules and severe itching. Prurigo occurs in association with various underlying diseases, such as diabetes, chronic renal failure, and internal malignancies. Atopic dermatitis is occasionally complicated by prurigo lesions. However, the pathology of prurigo is completely undefined. We demonstrate that repeated intradermal administration of Ag to IgE-transgenic mice causes persistent and pruritic papulonodular skin lesions mimicking prurigo. Skin lesions were histopathologically characterized by irregular acanthosis and dermal cellular infiltrates comprising eosinophils, mononuclear cells, and basophils, with epidermal nerve fiber sprouting. In vivo depletion of basophils alleviated skin reactions, indicating that the inflammation is basophil dependent. Unexpectedly, STAT6 signaling was unnecessary for skin lesion development if IgE was present. Moreover, the absence of STAT6 signaling exacerbated the inflammation, apparently as the result of impaired generation of an M2-type anti-inflammatory macrophage response. These results provide novel insights into the pathologic mechanisms underlying prurigo. Although basophils are indispensable for prurigo-like inflammation, Th2 immunity mediated by STAT6 appears to play a protective role, and therapies targeting Th2-type cytokines may risk aggravating the inflammation.

[Pathogenesis of prurigo nodularis]. / Pathogenese der Prurigo nodularis.

BACKGROUND: Prurigo nodularis is a chronic reaction pattern associated with severe pruritus that markedly affects the quality of life in patients. PATHOGENESIS: The pathogenesis of prurigo nodularis is not completely clear. Patients have an increased number of substance P and calcitonin gene-related peptide positive nerves in the dermis. Eosinophils and mast cells are in close vicinity to peripheral nerves and increased in numbers in the inflammatory infiltrate in prurigo nodularis. Nerve growth factor (NGF) is increased in lesional skin of patients and can be released by mast cells and eosinophils. In addition, NGF modulates the functional activity of mast cells and eosinophils. Recently, higher levels of the novel pruritic cytokine IL-31 were found in the skin of patients with prurigo nodularis than other pruritic skin diseases. CONCLUSION: The pathogenesis of prurigo nodularis seems to be regulated by immunological and neuronal plasticity which will be highlighted in the current article.

Atopic dermatitis/atopic eczema.

Atopic dermatitis was described in 1933 but exists since antiquity. We review descriptions of a childhood skin disease compatible with our modern diagnosis of atopic dermatitis, in ancient medicine and in nineteenth century dermatology texts. We identify Hebra's prurigo and Besnier's diathetic prurigo as forerunners of atopic dermatitis, the latter being a synthesis of infantile eczema and prurigo. The pathogenic theories which link atopic dermatitis to humoralistic medicine, to digestive diseases, to allergy may have had consequences on today's reluctance to consider atopic dermatitis as a skin disorder, the treatment of which relies mainly on topicals.