Karola Stieler

Profiling of Alopecia Areata Autoantigens Based on Protein Microarray Technology

Protein biochips have a great potential in future parallel processing of complex samples as a research tool and in diagnostics. For the generation of protein biochips, highly automated technologies have been developed for cDNA expression library production, high throughput protein expression, large scale analysis of proteins, and protein microarray generation. Using this technology, we present here a strategy to identify potential autoantigens involved in the pathogenesis of alopecia areata, an often chronic disease leading to the rapid loss of scalp hair. Only little is known about the putative autoantigen(s) involved in this process. By combining protein microarray technology with the use of large cDNA expression libraries, we profiled the autoantibody repertoire of sera from alopecia areata patients against a human protein array consisting of 37,200 redundant, recombinant human proteins. The data sets obtained from incubations with patient sera were compared with control sera from clinically healthy persons and to background incubations with anti-human IgG antibodies. From these results, a smaller protein subset was generated and subjected to qualitative and quantitative validation on highly sensitive protein microarrays to identify novel alopecia areata-associated autoantigens. Eight autoantigens were identified by protein chip technology and were successfully confirmed by Western blot analysis. These autoantigens were arrayed on protein microarrays to generate a disease-associated protein chip. To confirm the specificity of the results obtained, sera from patients with psoriasis or hand and foot eczema as well as skin allergy were additionally examined on the disease-associated protein chip. By using alopecia areata as a model for an autoimmune disease, our investigations show that the protein microarray technology has potential for the identification and evaluation of autoantigens as well as in diagnosis such as to differentiate alopecia areata from other skin diseases.

Autosomal dominant inheritance in a large family with focal facial dermal dysplasia (Brauer–Setleis syndrome)†

Focal facial dermal dysplasia (FFDD) (OMIM 227260) is a rare ectodermal disorder characterized by congenital bitemporal scar‐like depressions resembling forceps marks and variable additional facial manifestations. No gene defects or gene loci for FFDD are known to date. We report on a large multi‐generational German family with typical characteristics of FFDD and provide a detailed clinical description of four affected individuals. They had large bitemporal discolored dermal depressions, sparse lateral eyebrows, abnormal eyelashes, and dysplastic and low‐set ears. Three of the four affected individuals had congenital horizontal nystagmus, which had hitherto only been reported in a single patient with FFDD. In contrast to previous assumptions about an autosomal recessive etiology of this disorder, this family provides further evidence that FFDD is inherited in an autosomal dominant mode. Although this family is not large enough to yield significant results in linkage analysis, it may, in combination with other families, contribute to the identification of a gene locus for this intriguing ectodermal disorder.

Optical coherent tomography: promising in vivo measurement of hair shaft cross section.

Variations in hair shaft morphology reflect ethnical diversity, but may also indicate internal diseases, nutritional deficiency, or hair and scalp disorders. The measurement and the follow-up of the hair shaft thickness over a defined period of time would be a valuable diagnostic tool in clinical practice. Standard light microscopy (LM) measurements require the epilation of hair shafts and frequently yield inaccurate values caused by the elliptic geometry of human hair shafts. Optical coherence tomography (OCT) is a noninvasive investigation method based on the principles of Michelson interferometry with a detection depth of approximately 1 mm in human skin. Two-dimensional images of the cross sections of tissue samples at a resolution of approximately 10 μm are produced, which allows convenient calculation of hair shaft thickness. To evaluate this new methodology for hair shaft thickness measurements, hair shafts taken from 28 healthy volunteers were analyzed by in vivo OCT and compared to standard in vitro LM measurements of hair shaft thickness. OCT yielded highly reproducible measurements of hair shaft thickness with a distinctly reduced variation compared to standard LM. This technique offers a unique opportunity for in vivo measurement and a follow-up of the kinetics of hair shaft thickness in humans during medical therapy.

Successful treatment of childhood cheilitis granulomatosa with infliximab

First described by Miescher in 1945, cheilitis granulomatosa (CG) is a rare infl ammatory disorder that is part of a larger group of diseases referred to as orofacial granulomatosis (OFG) [ 1 ] . The incidence of CG is estimated to be 0.08 % [ 2 ] . Clinically, it is characterized by painless, sometimes asymmetric, diffuse swelling of one or both lips. Following the fi rst episode, the edema typically subsides completely, whereas it tends to persist after subsequent fl ares. Cheilitis granulomatosa frequently occurs as one of several clinical manifestations of Melkersson-Rosenthal syndrome (MRS). Although MRS is commonly monosymptomatic, associated symptoms also include lingua plicata (30–50 %) and facial nerve palsy (20–60 %) [ 3 ] . In addition, cheeks, eyelids, forehead, or palate may be similarly affected by recurrent or persistent infl ammatory edematous swelling (pareiitis granulomatosa, blepharitis granulomatosa, metopitis granulomatosa, uranitis granulomatosa). Monosymptomatic CG may also be regarded as OFG when associated with Crohn’s disease, an association that has been reported to occur in 20–50 % of cases [ 4, 5 ] . Given its unknown etiology, treatment of OFG is challenging. To date, no guidelines or recommendations for standardized treatment have been issued. There have been a few case reports describing the use of anti-TNF antibodies such as infl iximab and adalimumab [ 1 ] . Herein, we report on the successful use of infl iximab in two childhood cases of OFG refractory to conventional therapies. A 12-year-old boy presented with a two-year history of erythematous orofacial swelling that prevented him from fully opening his mouth, and had thus resulted in a speech impediment. Based on clinical and histological fi ndings, he was diagnosed with CG. Crohn’s disease was ruled out by colonoscopy. Previous therapies with systemic corticosteroids (pulse therapy with prednisolone 50 mg), clofazimine 100 mg daily for six months, and systemic tetracycline for six weeks had been unsuccessful. The boy was subsequently treated with off-label infl iximab (5 mg/kg body weight [BW] i.v. at eight-week intervals) for twelve months. After three months of treatment, there was marked improvement in orofacial swelling and erythema, as well as a signifi cant decrease in granulomatous infi ltrates (Figure 1 ). Another 12-year-old boy presented with a three-year history of recurrent orofacial swelling and erythema. Since the seventh year of life, he had experienced growth retardation (138 cm, weight 26.5 kg, below the third percentile). The diagnosis of CG was histologically confi rmed. Due to the aforementioned growth retardation as well as bloody stools, a colonoscopy was performed, and revealed Crohn’s disease. This patient was likewise started on with infl iximab 5 mg/kg BW i.v. The fi rst six doses were given at eight-week intervals. After four months, the swelling of the cheeks had diminished, and his overall health had also signifi cantly improved, as

Symmetrical inflammatory erosive plaques and blisters in an infant

A 1-year and 4-month-old girl presented to our pediatric dermatology clinic with a several-months history of recurrent infl ammatory, erosive perioral and perianal plaques and crusts, as well as stomatitis and acral blisters. A previous biopsy taken to rule out Langerhans cell histiocytosis had been consistent with bullous impetigo. Treatment with topical and systemic antibiotics had provided only minimal, short-term improvement. In addition, the patient’s mother also reported that the little girl had had frequent watery stools and exhibited a refusal to eat.

Erythematosquamöse Erkrankungen in der Adoleszenz@@@Erythematosquamous dermatoses in adolescence

ZusammenfassungDas differenzialdiagnostische Spektrum der erythematosquamösen Hauterkrankungen in der Adoleszenz ist sehr vielfältig. Besonderheiten in klinischer Präsentation und Symptomatik, psychosoziale Belastung der Betroffenen und seltenere Krankheitsbilder stellen für den behandelnden Kinderdermatologen häufig eine besondere Aufgabe und Herausforderung dar. Diese Übersicht wird die Besonderheiten klassischer erythematosquamöser Dermatosen bei Manifestation in der Adoleszenz wie auch weniger geläufige Krankheitsbilder mit Manifestation in dieser Lebensphase ansprechen.AbstractErythematosquamous dermatoses in adolescents comprise a wide range of differential diagnoses. Age-typical variations of the clinical manifestation, the need to differentiate common conditions from rare diseases as well as the tremendous psychosocial impact which the patients perceive especially in this vulnerable period of life can become major challenges for pediatric dermatologists. This article summarizes key features of common erythematosquamous dermatoses and less frequent skin diseases occurring during adolescence.Erythematosquamous dermatoses in adolescents comprise a wide range of differential diagnoses. Age-typical variations of the clinical manifestation, the need to differentiate common conditions from rare diseases as well as the tremendous psychosocial impact which the patients perceive especially in this vulnerable period of life can become major challenges for pediatric dermatologists. This article summarizes key features of common erythematosquamous dermatoses and less frequent skin diseases occurring during adolescence.

Erythematosquamous dermatoses in adolescence

ZusammenfassungDas differenzialdiagnostische Spektrum der erythematosquamösen Hauterkrankungen in der Adoleszenz ist sehr vielfältig. Besonderheiten in klinischer Präsentation und Symptomatik, psychosoziale Belastung der Betroffenen und seltenere Krankheitsbilder stellen für den behandelnden Kinderdermatologen häufig eine besondere Aufgabe und Herausforderung dar. Diese Übersicht wird die Besonderheiten klassischer erythematosquamöser Dermatosen bei Manifestation in der Adoleszenz wie auch weniger geläufige Krankheitsbilder mit Manifestation in dieser Lebensphase ansprechen.AbstractErythematosquamous dermatoses in adolescents comprise a wide range of differential diagnoses. Age-typical variations of the clinical manifestation, the need to differentiate common conditions from rare diseases as well as the tremendous psychosocial impact which the patients perceive especially in this vulnerable period of life can become major challenges for pediatric dermatologists. This article summarizes key features of common erythematosquamous dermatoses and less frequent skin diseases occurring during adolescence.Erythematosquamous dermatoses in adolescents comprise a wide range of differential diagnoses. Age-typical variations of the clinical manifestation, the need to differentiate common conditions from rare diseases as well as the tremendous psychosocial impact which the patients perceive especially in this vulnerable period of life can become major challenges for pediatric dermatologists. This article summarizes key features of common erythematosquamous dermatoses and less frequent skin diseases occurring during adolescence.

Erythematosquamöse Erkrankungen in der Adoleszenz

ZusammenfassungDas differenzialdiagnostische Spektrum der erythematosquamösen Hauterkrankungen in der Adoleszenz ist sehr vielfältig. Besonderheiten in klinischer Präsentation und Symptomatik, psychosoziale Belastung der Betroffenen und seltenere Krankheitsbilder stellen für den behandelnden Kinderdermatologen häufig eine besondere Aufgabe und Herausforderung dar. Diese Übersicht wird die Besonderheiten klassischer erythematosquamöser Dermatosen bei Manifestation in der Adoleszenz wie auch weniger geläufige Krankheitsbilder mit Manifestation in dieser Lebensphase ansprechen.AbstractErythematosquamous dermatoses in adolescents comprise a wide range of differential diagnoses. Age-typical variations of the clinical manifestation, the need to differentiate common conditions from rare diseases as well as the tremendous psychosocial impact which the patients perceive especially in this vulnerable period of life can become major challenges for pediatric dermatologists. This article summarizes key features of common erythematosquamous dermatoses and less frequent skin diseases occurring during adolescence.Erythematosquamous dermatoses in adolescents comprise a wide range of differential diagnoses. Age-typical variations of the clinical manifestation, the need to differentiate common conditions from rare diseases as well as the tremendous psychosocial impact which the patients perceive especially in this vulnerable period of life can become major challenges for pediatric dermatologists. This article summarizes key features of common erythematosquamous dermatoses and less frequent skin diseases occurring during adolescence.

Klassifizierung anhand klinischer Muster

ZusammenfassungHaarausfall im Kindesalter ist in der Regel für den behandelnden Kinderarzt und Dermatologen eine diagnostische und therapeutische Herausforderung. Daher ist es sinnvoll, zunächst anhand des klinischen Musters eine Klassifizierung vorzunehmen, um dann mittels trichologischer Diagnostik weitere Differenzialdiagnosen abzugrenzen [1].

Skin manifestations associated with chronic recurrent multifocal osteomyelitis in a 9-year-old girl

without psoriasis vulgaris is caused by deficiency of interleukin-36 receptor antagonist. J Invest Dermatol 2013; 133:2514-21. 2. Navarini AA, Valeyrie-Allanore L, Setta-Kaffetzi N, Barker JN, Capon F, Creamer D, et al. Rare variations in IL36RN in severe adverse drug reactions manifesting as acute generalized exanthematous pustulosis. J Invest Dermatol 2013;133:1904-7. 3. Setta-Kaffetzi N, Navarini AA, Patel VM, Pullabhatla V, Pink AE, Choon SE, et al. Rare pathogenic variants in IL36RN underlie a spectrum of psoriasis-associated pustular phenotypes. J Invest Dermatol 2013;133:1366-9. 4. Carrier Y, Ma HL, Ramon HE, Napierata L, Small C, O’Toole M, et al. Inter-regulation of Th17 cytokines and the IL-36 cytokines in vitro and in vivo: implications in psoriasis pathogenesis. J Invest Dermatol 2011;131:2428-37. 5. Torigo S, Ihara T, Kamiya H. IL-12, IFN-gamma, and TNF-alpha released from mononuclear cells inhibit the spread of varicella-zoster virus at an early stage of varicella. Microbiol Immunol 2000;44:1027-31.