Dissecting susceptibility from exogenous triggers: the model of alopecia areata and associated inflammatory skin diseases

Garzorz, Natalie; Al-Sisi, Mohammed; Todorova, Antonia; Atenhan, A.; Thomas, Jenny; Lauffer, Felix; Ring, Johannes; Schmidt‐Weber, Carsten B.; Biedermann, Tilo; Eyerich, Stefanie; Eyerich, Kilian

doi:10.1111/jdv.13325

Cited by 22 publications

(17 citation statements)

References 34 publications

(68 reference statements)

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“…A genetic predisposition to multiple autoimmune disease development could also be suspected in our patient, considering his positive family history. The association of either AA or EBA with other autoimmune disorders has been described, although we did not find reports of patients with both AA and EBA. In this context, the occurrence of EBA during SADBE treatment may represent a simple coincidence in a patient already having another autoimmune disease.…”

Section: Discussioncontrasting

confidence: 84%

Childhood epidermolysis bullosa acquisita during squaric acid dibutyl ester immunotherapy for alopecia areata

et al. 2016

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Epidermolysis bullosa acquisita (EBA) is a rare acquired subepidermal blistering disease associated with autoantibodies against type VII collagen. Although EBA manifests more frequently in adults, it can occur in childhood. We describe a 6-year-old boy who developed the inflammatory variant of EBA shortly after initiation of immunotherapy with squaric acid dibutyl ester (SADBE) for scalp alopecia areata. The disease rapidly regressed following SADBE discontinuation and starting combined steroid and dapsone therapy, and never recurred after treatment tapering and withdrawal. The association of EBA with other autoimmune diseases is common, but EBA occurring during alopecia areata has not been described previously. The development of EBA during SADBE treatment is also notable: the clinical history and therapeutic response in our patient point to a possible role of SADBE in EBA onset.

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Section: Discussioncontrasting

confidence: 84%

Childhood epidermolysis bullosa acquisita during squaric acid dibutyl ester immunotherapy for alopecia areata

et al. 2016

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“…A retrospective study in Taiwan found that patients with alopecia areata had higher hazard ratios for autoimmune diseases such as rheumatoid arthritis, systemic lupus erythematosus and psoriasis within the 3-year follow-up period than healthy controls 44 . In addition, increased prevalence of other forms of inflammatory skin disease such as atopic dermatitis, vitiligo, psoriasis and lichen planus were found than in controls, suggesting that patients with alopecia areata are at increased risk of developing variety of T-cell driven inflammatory skin diseases 45 . Severe alopecia areata might be accompanied by nail changes 20 .…”

Section: Concurrent Diseasesmentioning

confidence: 99%

Alopecia areata

Pratt

King

Messenger

et al. 2017

Nat Rev Dis Primers

576

528

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Alopecia areata is an autoimmune disorder characterized by transient, non-scarring hair loss and preservation of the hair follicle. Hair loss can take many forms ranging from loss in well-defined patches to diffuse or total hair loss, which can affect all hair bearing sites. Patchy alopecia affecting the scalp is the most common type. Alopecia areata affects nearly 2% of the general population at some point during their lifetime. Skin biopsies of alopecia areata affected skin show a lymphocytic infiltrate in and around the bulb or the lower part of the hair follicle in anagen (hair growth) phase. A breakdown of immune privilege of the hair follicle is thought to be an important driver of alopecia areata. Genetic studies in patients and mouse models showed that alopecia areata is a complex, polygenic disease. Several genetic susceptibility loci were identified associated with signaling pathways that are important to hair follicle cycling and development. Alopecia areata is usually diagnosed based on clinical manifestations, but dermoscopy and histopathology can be helpful. Alopecia areata is difficult to manage medically, but recent advances in understanding the molecular mechanisms have revealed new treatments and the possibility of remission in the near future.

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“…Therefore, this older assay variant may be recruited to dissect the relative functional contribution of patient genetics to the pathobiology of AA initiation [5,112,113,114] (Supplementary text 5). …”

Section: Murine Models Of Aamentioning

confidence: 99%

Alopecia areata: Animal models illuminate autoimmune pathogenesis and novel immunotherapeutic strategies

Gilhar

Schrum

Etzioni³

et al. 2016

Autoimmunity Reviews

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One of the most common human autoimmune diseases, alopecia areata (AA), is characterized by sudden, often persisting and psychologically devastating hair loss. Animal models have helped greatly to elucidate critical cellular and molecular immune pathways in AA. The two most prominent ones are inbred C3H/HeJ mice which develop an AA-like hair phenotype spontaneously or after experimental induction, and healthy human scalp skin xenotransplanted onto SCID mice, in which a phenocopy of human AA is induced by injecting IL-2-stimulated PBMCs enriched for CD56+/NKG2D+ cells intradermally. The current review critically examines the pros and cons of the available AA animal models and how they have shaped our understanding of AA pathobiology, and the development of new therapeutic strategies. AA is thought to arise when the hair follicle’s (HF) natural immune privilege (IP) collapses, inducing ectopic MHC class I expression in the HF epithelium and autoantigen presentation to autoreactive CD8+ T cells. In common with other autoimmune diseases, upregulation of IFN-γ and IL-15 is critically implicated in AA pathogenesis, as are NKG2D and its ligands, MICA, and ULBP3. The C3H/HeJ mouse model was used to identify key immune cell and molecular principles in murine AA, and proof-of-principle that Janus kinase (JAK) inhibitors are suitable agents for AA management in vivo, since both IFN-γ and IL-15 signal via the JAK pathway. Instead, the humanized mouse model of AA has been used to demonstrate the previously hypothesized key role of CD8+ T cells and NKG2D+ cells in AA pathogenesis and to discover human-specific pharmacologic targets like the potassium channel Kv1.3, and to show that the PDE4 inhibitor, apremilast, inhibits AA development in human skin. As such, AA provides a model disease, in which to contemplate general challenges, opportunities, and limitations one faces when selecting appropriate animal models in preclinical research for human autoimmune diseases.

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Dissecting susceptibility from exogenous triggers: the model of alopecia areata and associated inflammatory skin diseases

Cited by 22 publications

References 34 publications

Childhood epidermolysis bullosa acquisita during squaric acid dibutyl ester immunotherapy for alopecia areata

Childhood epidermolysis bullosa acquisita during squaric acid dibutyl ester immunotherapy for alopecia areata

Alopecia areata

Alopecia areata: Animal models illuminate autoimmune pathogenesis and novel immunotherapeutic strategies

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