Search

Alopecia areata is a common condition that leads to nonscarring hair loss. It can be severe and lead to complete hair loss of the scalp or the whole body. In more severe cases, the disease can be very recalcitrant to treatment and result in a significant impairment of the quality of life of the patients. In recent years, there is increasing evidence on the potential of janus kinase (JAK) inhibitors to treat alopecia areata. In the beginning, this was based on case reports, but later, this potential was further established by large case series and in vitro and in vivo data. It is on this basis that JAK inhibitors are being tested specifically for the treatment of alopecia areata in phase 3, randomized, placebo-controlled trials, raising hopes that there will soon be a JAK inhibitor approved by the US Food and Drug Administration (FDA) for the treatment of alopecia areata. Here we provide a review of the information available on the use of JAK inhibitors to treat alopecia areata, and the potential benefits and risks of this class of medications.Die Alopecia areata ist eine häufige Störung, die zu nicht vernarbendem Haarausfall führt. Sie kann einen schweren Verlauf nehmen und bis zu einem vollständigen Verlust der Haare am Kopf oder am Körper führen. In solchen schwereren Fällen spricht die Erkrankung unter Umständen kaum auf eine Therapie an, was die Lebensqualität betroffener Patienten erheblich beeinträchtigt. Seit einigen Jahren zeichnet sich zunehmend ab, dass Januskinase(JAK)-Inhibitoren eine Option in der Therapie der Alopecia areata sein können. Einzelfallberichte lieferten erste Hinweise, in der Folge konnte das therapeutische Potenzial durch große Fallserien sowie In-vitro- und In-vivo-Daten diese Hypothese weiter untermauern. Vor diesem Hintergrund werden JAK-Inhibitoren aktuell in randomisierten, placebokontrollierten Phase-3-Studien speziell in der Therapie der Alopecia areata geprüft, was die Hoffnung nährt, dass es bald einen von der US Food and Drug Administration (FDA) zugelassenen JAK-Inhibitor für die Behandlung der Alopecia areata geben wird. Der vorliegende Beitrag fasst die verfügbaren Daten zum Einsatz von JAK-Inhibitoren bei Alopecia areata zusammen. Dabei wird auf den potenziellen Nutzen und die möglichen Risiken dieser Medikamentenklasse eingegangen.

We report the case of a 46-year-old woman who has suffered from severe atopic dermatitis since early childhood and from alopecia areata totalis since she was 18 years old, which has now developed into alopecia areata universalis. After the introduction of therapy with the monoclonal antibody dupilumab, renewed hair growth of the scalp, face and lower legs was observed. Dupilumab blocks the α‑subunit of interleukin (IL)-4 receptor and prevents the signaling cascade of IL‑4 and IL-13. This leads to a reduction of Th2 immune response. The severe eczema and itching with difficulties falling and staying asleep decreased after just 14 days. The patient tolerates the drug without significant side effects and has a significantly improved quality of life. Patients with severe atopic dermatitis and alopecia areata could benefit twice from the use of dupilumab in the future.Berichtet wird über eine 46-jährige Patientin, die seit ihrer frühen Kindheit unter einer schweren atopischen Dermatitis leidet und seit ihrem 18. Lebensjahr unter einer Alopecia areata totalis, die mittlerweile in eine Alopecia areata universalis übergegangen ist. Durch die Einleitung einer Therapie mit dem monoklonalen Antikörper Dupilumab wurde erneutes Haarwachstum am Kapillitium, im Gesicht und an den Unterschenkeln beobachtet. Dupilumab blockiert die α‑Untereinheit des IL(Interleukin)-4-Rezeptors, unterbindet die Signalkaskade von IL‑4 und IL-13 und führt so zu einer reduzierten Th2-Immunantwort. Die schwere Ausprägung der Ekzeme und der Juckreiz mit Ein- und Durchschlafstörungen sind bereits 14 Tage nach Beginn der Einnahme zurückgegangen. Die Patientin verträgt das Medikament ohne wesentliche Nebenwirkungen, ihre Lebensqualität ist deutlich verbessert. Patienten mit einer schweren atopischen Dermatitis und einer Alopecia areata könnten von Dupilumab in Zukunft doppelt profitieren.

Diese retrospektive Analyse untersucht die Behandlung von Patienten mit Alopecia areata in der Klinik und Poliklinik für Dermatologie, Venerologie und Allergologie der Universitätsklinik Würzburg mit Diphenylcyclopropenon und beleuchtet Faktoren der durch die Behandlung beeinflussten Lebensqualität., This study evaluates the efficacy of the treatment of alopecia areata in the dermatology department of the university clinic in Würzburg, Germany and shows prognostic factors that may be detrimental in regards to a positive outcome. Furthermore, the influence of the therapy's side-effects on everyday life are shown.

A 64-year old man developed alopecia universalis after one month of treatment with metformin and sitagliptin, a dipeptidyl peptidase‑4 (DPP-4) inhibitor. Diabetes treatment was changed to another genericum of sitagliptin and dapagliflozin. Following our recommendation, sitagliptin was interrupted and monotherapy with dapagliflozin was continued. After 6 weeks, sitagliptin was reassumed due to unsatisfactory diabetes control. Alopecia did not improve. We suspect a connection between DPP‑4 inhibition and development of alopecia due to its immunological potential. We assume that the treatment interruption might have been too short to induce regrowth of hair. DPP‑4 may result in both inhibition and activation of the immune system.Ein 64-jähriger Patient entwickelte 1 Monat nach Therapieeinleitung mit Sitagliptin, einem Dipeptidylpeptidase-4(DPP‑4)-Inhibitor, und Metformin eine Alopecia universalis. Die Therapie des Diabetes wurde auf das Sitagliptin eines anderen Herstellers und Dapagliflozin umgestellt. Auf unser Anraten wurde Sitagliptin abgesetzt und eine Monotherapie mit Dapagliflozin fortgeführt. Nach 6 Wochen war eine erneute Therapie mit Sitagliptin bei unzureichend eingestelltem Diabetes notwendig. Die Alopezie persistierte. Aufgrund des immunologischen Interaktionspotenzials vermuten wir eine Assoziation zwischen DPP-4-Inhibition und der Alopezie. Der kurze therapiefreie Zeitraum scheint zu gering, um ein erneutes Haarwachstum zu beobachten. DPP‑4 kann sowohl eine Inhibition als auch Aktivierung des Immunsystems bewirken.

We present a case of a 46-year-old woman suffering from active inflammatory alopecia areata universalis. After frustrating use of topical and systemic glucocorticoids, cream PUVA (psoralen and ultraviolet A) therapy and dithranol in increasing dosage, the patient was treated with 2 × 5 mg per day tofacitinib per os. After about 4-6 months, hair growth commenced, which led to full regrowth of scalp hair over the 18 months of therapy, which was well tolerated. The case shows impressively that the off-label application of tofacitinib is a therapeutic option for alopecia areata.Wir präsentieren den Fall einer 46-jährigen Patientin, die an einer entzündlich aktiven Alopecia areata universalis leidet. Nach frustranem Einsatz von topischen und systemischen Glukokortikoiden, einer Creme-PUVA-Therapie und Dithranol in aufsteigender Dosierung wurde die Patientin mit 2‑mal 5 mg pro Tag Tofacitinib per os behandelt. Nach ca. 4 bis 6 Monaten zeigte die Patientin ein Haarwachstum, das bei guter Verträglichkeit bis zum 18. Therapiemonat zur vollständigen Wiederbehaarung geführt hat. Der Fall zeigt eindrucksvoll, dass die Off-label-Anwendung von Tofacitinib eine potenzielle therapeutische Option in der Indikation Alopecia areata darstellen kann.

Leukotrichia can be caused by a variety of metabolic and inflammatory diseases. Canine alopecia areata is a rare multifactorial benign non-scarring alopecia. This case report describes a seasonally recurrent leukotrichia associated with alopecia areata in a German shepherd dog. Important differential diagnoses were ruled out and histopathology finally confirmed the diagnosis of alopecia areata. Topical tacrolimus and hydrocortisone aceponate were ineffective. The cause for the seasonal character in this case remained undetermined.

Für das Verständnis der Pathogenese entzündlicher Hauterkrankungen ist die Zusammensetzung des zellulären Entzündungsinfiltrates und die Verteilung der Entzündungszellen von wesentlicher Bedeutung. In Anbetracht der chemotaktischen Funktion der Chemokine liegt die Annahme nahe, dass das zelluläre Infiltrationsmuster in entzündlichen Hauterkrankungen das Expressionsmuster von Chemokinen und umgekehrt widerspiegelt. Die Infiltrationsroute der Leukozyten in die Haut erfolgt immer vom Lumen dermaler Gefäße in das dermale Milieu und ggf. weiter in das epidermale Kompartiment (sog. Epidermotropismus). Die Migration inflammatorischer Zellen über die Grenzen unterschiedlicher Hautkompartimente hinweg ist einzigartig und präsentiert ein ideales Modell, um die chemotaktischen Cytokin- bzw. Chemokinfunktionen zu evaluieren. Anhand verschiedener ausgewählter Hautdermatosen (Wundheilung, Psoriasis, Alopecia areata) wurden die unterschiedlichen Expressionsmuster einer Auswahl von Chemokinen untersucht. Dabei nehmen Chemokine, die von Endothelzellen exprimiert bzw. sezerniert werden, eine zentrale Rolle ein, da sie eine „Pförtnerfunktion“ ausführen. Diese Funktion ist entscheidend bei der Rekrutierung und Akkumulation der für das Erkrankungsbild und bei reparativen Vorgängen der Wundheilung spezifischen Leukozytensubpopulation ins dermale bzw. epidermale Gewebe, The composition of the cellular inflammatory infiltrates and the distribution of inflammatory cells is essential for the understanding of the pathogenesis of inflammatory skin diseases. In view of the chemotactic function of chemokines we assume that the cellular infiltration pattern in inflammatory skin diseases reflects the expression patterns of chemokines and vice versa. The route of leukocyte infiltration into the skin is always directed from the lumen of dermal vessels in the dermal milieu and in some cases further into the epidermal compartment (so-called epidermotropism). The migration of inflammatory cells across the borders of different skin compartments is unique and represents an ideal model to evaluate the chemotactic function of cytokines or chemokines. In various representative dermatoses (wound healing, psoriasis, alopecia areata) we investigated the different expression patterns of selected chemokines. Chemokines, expressed or secreted by endothelial cells, play an important role because they exert a "gatekeeper function". This is crucial in the recruitment and accumulation pattern of the disease and repair processes of wound-specific leukocyte subpopulation, which invade the dermal and epidermal compartment.

Acquired disorders of hair growth in women may present clinically either as effluvium or alopecia. The relevant pathologies include androgenetic alopecia, postpartum effluvium, tinea capitis, trichotillomania and alopecia areata.

Alopecia areata is a common disease, but for ethical reasons it seems difficult to perform large-scale studies to elucidate the pathogenesis and to develop new therapeutic approaches in man. It is therefore helpful to develop appropriate animal models. The Dundee experimental bald rat (DEBR) and the C3H/HeJ mouse are well-established animal models for alopecia areata and can be used for the study of genetic aspects, pathogenesis and therapy of the disease. In C3H/HeJ mice alopecia areata can be experimentally induced by grafting lesional skin from an affected mouse to a histocompatible recipient which offers the possibility to study the influence of various factors on the development of the disease. Studies on the C3H/HeJ mouse and the DEBR have corroborated the concept that alopecia areata is a T-cell mediated autoimmune disease and various steps and aspects of the pathogenesis have been elucidated. Based on this knowledge new therapeutic options may be developed such as inhibition of lymphocyte-homing by an anti-CD44v10 antibody, or inhibition of costimulation by monoclonal antibodies. Therapeutic studies in the C3H/HeJ mouse and the DEBR suggest that alopecia areata can be treated by topical tacrolimus but treatment in humans may only be successful after development of an improved vehicle that facilitates penetration of tacrolimus down to the hair bulb. Current investigations in mice are designed to elucidate the mechanisms how contact sensitizers act in the treatment of alopecia areata, and this will hopefully lead to the development of more specific approaches based on the beneficial effect of contact sensitizers.

We report for the first time on hair regrowth in alopecia areata of the scalp achieved with the 308-nm xenon-chloride excimer laser in a prospective side-by-side trial. The alopecia areata had shown progression over a period of three years, and various treatments had not been effective. Out of a number of affected areas, one representative lesion was chosen; one half of it was treated, the other half remained untreated. After 27 sessions (200 - 4000 mJ/cm2, cumulative dose 52.6 J/cm2) over 3 months, only the treated area showed hair growth; which suggests that this was most probably not a spontaneous remission.

A 35-year-old woman presented with severe recalcitrant atopic dermatitis, in association with disseminated mollusca contagiosa and alopecia areata universalis. After several weeks of systemic interferon gamma, which was administered subcutaneously,the viral infection cleared and, surprisingly, four weeks after starting treatment hair re-growth was observed. Complete remission of alopecia areata was documented few weeks later and persists. After four cycles of high-dose intravenous immunoglobulin, a sustained remission of the atopic dermatitis was achieved.

First reports about the use of the excimer laser in dermatology date back to 1997. It is seen as an improvement on conventional phototherapy and photochemotherapy because of the lower cumulative UV-dose involved, the shorter time frame required for treatment and the option of targeting individual lesions without affecting the surrounding healthy skin. In addition to the indications of psoriasis vulgaris, vitiligo and atopic eczema (for which there is now FDA approval in the US), the spectrum of possible uses for the excimer laser is growing rapidly, especially in the field of light-sensitive dermatoses. Case studies so far have ranged from post-operative hypopigmentation to acne vulgaris and from alopecia areata to parapsoriasis en plaque. The foremost priorities in the future will be to evaluate reproducible therapeutic regimens with realistic prospects of success in large-scale studies; assess potential iatrogenic risks in treatment; develop pathogenetic models for the mechanism of action; and define therapeutic approaches to new indications. This paper summarizes the publications to date and discusses our observations and experiences.

Alopecia areata is a T-cell mediated autoimmune disease directed against an unknown auto antigen of the hair follicle. There is a genetic predisposition to develop alopecia areata, whereas environmental triggers have so far not been identified. The diagnosis can be established by characteristic clinical features of alopecia areata including its severe forms alopecia areata totalis and universalis. Nail changes may help confirm the diagnosis. On rare occasions a histopathological examination may be necessary, whereas other laboratory investigations are unnecessary. Because of the high rate of spontaneous remission, the efficacy of a rational treatment of alopecia areata has to be proven in controlled studies and it should be associated with only minor side effects. According to the rules of evidence-based medicine, treatment with a contact sensitizer is at present the most effective treatment of alopecia areata showing only mild side effects. However, it is time-consuming and in some cases ineffective, making it desirable to develop new, more specific forms of treatment.

The Rapunzel syndrome is a rare manifestation of a gastric trichobezoar with a "tail" extending throughout the small intestine and sometimes even to the colon. We report on the surgical removal of such a bezoar in a 4-year-old patient by gastrotomy--the third published case in the German literature. The syndrome is mainly seen in young girls with trichophagia psychodynamically associated with early childhood deprivation and a high comorbidity of serious pediatric psychiatric disorders. The symptoms are nonspecific and may mimic those of other pathologic gastrointestinal conditions. Clinical characteristics are a movable mass in the epigastrium and alopecia. The therapy of choice is surgery of the trichobezoar together with the whole intestinal "tail," as in most cases endoscopic removal fails due to the large extension. Early diagnosis and treatment of the Rapunzel syndrome is of eminent importance in order to avoid later fatal complications such as gastric perforation and intestinal necroses. Intensive psychiatric follow-up is mandatory for preventing relapses.

Hair loss includes excessive shedding of hair (effluvium) and the alopecias, in which there is a decrease in the amount of hair. Both may occur diffusely, or in a circumscribed manner. The localization and pattern of circumscribed hair loss may give a clue to its cause. On the basis of morphologic criteria the alopecias are further classified into non-scarring and scarring types. Non-scarring alopecias (diffuse alopecia, androgenetic alopecia, alopecia areata) are essentially hair cycling disorders, while scarring alopecias result from irreversible destruction of the hair follicles with recognizable loss of follicular osita. Scalp biopsy should be an early step in the evaluation of any case of alopecia, in which scarring is suspected. Too little scalp hair is not a vital problem, but represents a major health care challenge. Only recently the psychological impact of hair loss has been appreciated by the medical community, though throughout history, too little hair has been a concern to mankind, and the object of cosmetic interest and quackery. Recent advances of the medical sciences have led to a better understanding of the underlying pathogenic processes and opened the venue to effective pharmacotherapy (minoxidil, finasteride) and technologies (autologous hair transplantation) for the treatment of the most common disorders. Together with the availability of such treatments, high technical standards for evaluating their efficacy have been developed and have become mandatory for appraisal of any hair growth promoting agent, both in clinical studies and in the individual patient.