Treatment options for leishmaniasis.

Leishmaniasis is broadly classified into three types: cutaneous, mucocutaneous and visceral. The visceral form is most dangerous and can result in death. Although leishmaniasis is an ancient disease, its treatment is still challenging. Several drugs, differing in their cost, toxicity, treatment duration and emergence of drug resistance, are used for different types of leishmaniasis. To overcome these limitations, the search for newer drugs and other treatments continues. In this article, we discuss conventional drugs, other treatments, including newer options such as immunotherapy and immunochemotherapy, and future prospects for leishmaniasis treatment.

Response durability after cessation of immune checkpoint inhibitors in patients with metastatic Merkel cell carcinoma: a retrospective multicenter DeCOG study.

BACKGROUND: Immune checkpoint inhibitors (ICI) have led to a prolongation of progression-free and overall survival in patients with metastatic Merkel cell carcinoma (MCC). However, immune-mediated adverse events due to ICI therapy are common and often lead to treatment discontinuation. The response duration after cessation of ICI treatment is unknown. Hence, this study aimed to investigate the time to relapse after discontinuation of ICI in MCC patients. METHODS: We analyzed 20 patients with metastatic MCC who have been retrospectively enrolled at eleven skin cancer centers in Germany. These patients have received ICI therapy and showed as best overall response (BOR) at least a stable disease (SD) upon ICI therapy. All patients have discontinued ICI therapy for other reasons than disease progression. Data on treatment duration, tumor response, treatment cessation, response durability, and tumor relapse were recorded. RESULTS: Overall, 12 of 20 patients (60%) with MCC relapsed after discontinuation of ICI. The median response durability was 10.0 months. Complete response (CR) as BOR to ICI-treatment was observed in six patients, partial response (PR) in eleven, and SD in three patients. Disease progression was less frequent in patients with CR (2/6 patients relapsed) as compared to patients with PR (7/11) and SD (3/3), albeit the effect of initial BOR on the response durability was below statistical significance. The median duration of ICI therapy was 10.0 months. Our results did not show a correlation between treatment duration and the risk of relapse after treatment withdrawal. Major reasons for discontinuation of ICI therapy were CR (20%), adverse events (35%), fatigue (20%), or patient decision (25%). Discontinuation of ICI due to adverse events resulted in progressive disease (PD) in 71% of patients regardless of the initial response. A re-induction of ICI was initiated in 8 patients upon tumor progression. We observed a renewed tumor response in 4 of these 8 patients. Notably, all 4 patients showed an initial BOR of at least PR. CONCLUSION: Our results from this contemporary cohort of patients with metastatic MCC indicate that MCC patients are at higher risk of relapse after discontinuation of ICI as compared to melanoma patients. Notably, the risk of disease progression after discontinuation of ICI treatment is lower in patients with initial CR (33%) as compared to patients with initial PR (66%) or SD (100%). Upon tumor progression, re-induction of ICI is a feasible option. Our data suggest that the BOR to initial ICI therapy might be a potential predictive clinical marker for a successful re-induction.

[Diagnosis and treatment of basal cell carcinoma : A question of the risk of recurrence]. / Diagnostik und Therapie des Basalzellkarzinoms : Eine Frage des Rezidivrisikos.

Basal cell carcinoma is the most common type of cancer in Central Europe and has a high medical relevance. Due to its high tendency of recurrence, an important parameter in the planning of therapy is the risk of recurrence. After clinical and histological diagnosis, the majority of tumors are treated surgically, although radiation and topical procedures are also possible therapeutic alternatives in certain constellations. Hedgehog inhibitors, a completely new class of substances, have recently been approved for rare metastatic and locally advanced diseases, thus significantly expanding the range of treatments. This article provides an overview of the current guideline-based diagnosis and therapy of basal cell carcinomas in Germany.

[WHO classification and clinical spectrum of cutaneous lymphomas]. / WHO-Klassifikation und klinisches Spektrum der kutanen Lymphome.

BACKGROUND: Cutaneous lymphomas are rare skin cancers with a wide clinical spectrum. OBJECTIVE: To give an overview of the current classification and the clinical spectrum of cutaneous lymphomas. MATERIAL AND METHODS: Analysis and summary of the current literature concerning the different entities of cutaneous lymphomas. RESULTS: A few modifications in the nomenclature of cutaneous lymphoma have been introduced in the revised version of the WHO classification 2016. In the last years new types of lymphomatoid papulosis were described. Moreover, two subgroups of folliculotropic mycosis fungoides are now mentioned. The CD4+ small/medium T­cell lymphoproliferative disorder is no longer classified as an overt lymphoma. As new entities the EBV+ mucocutaneous ulcer, an EBV-associated diffuse large B­cell lymphoma (not otherwise specified) and a primary cutaneous acral CD8+ T­cell (provisional) lymphoma are being considered. CONCLUSION: The classification of cutaneous lymphomas is based on the revised version of the WHO classification (2016). The clinical pathological correlation is an elementary component for correct diagnosis.

Radiosensitization by BRAF inhibitor therapy-mechanism and frequency of toxicity in melanoma patients.

BACKGROUND: Recent evidence suggests that ionizing radiation may be associated with unexpected side-effects in melanoma patients treated with concomitant BRAF inhibitors. A large multicenter analysis was carried out to generate reliable safety data and elucidate the mechanism. METHODS: A total of 161 melanoma patients from 11 European skin cancer centers were evaluated for acute and late toxicity, of whom 70 consecutive patients received 86 series of radiotherapy with concomitant BRAF inhibitor therapy. To further characterize and quantify a possible radiosensitization by BRAF inhibitors, blood samples of 35 melanoma patients were used for individual radiosensitivity testing by fluorescence in situ hybridization of chromosomal breaks after ex vivo irradiation. RESULTS: With radiotherapy and concomitant BRAF inhibitor therapy the rate of acute radiodermatitis ≥2° was 36% and follicular cystic proliferation was seen in 13% of all radiotherapies. Non-skin toxicities included hearing disorders (4%) and dysphagia (2%). Following whole-brain radiotherapy, rates of radiodermatitis ≥2° were 44% and 8% (P < 0.001) for patients with and without BRAF inhibitor therapy, respectively. Concomitant treatment with vemurafenib induced acute radiodermatitis ≥2° more frequently than treatment with dabrafenib (40% versus 26%, P = 0.07). In line with these findings, analysis of chromosomal breaks ex vivo indicated significantly increased radiosensitivity for patients under vemurafenib (P = 0.004) and for patients switched from vemurafenib to dabrafenib (P = 0.002), but not for patients on dabrafenib only. No toxicities were reported after stereotactic treatment. CONCLUSION: Radiotherapy with concomitant BRAF inhibitor therapy is feasible with an acceptable increase in toxicity. Vemurafenib is a more potent radiosensitizer than dabrafenib.

Characterizing psychosocial distress in melanoma patients using the expert rating instrument PO-Bado SF.

BACKGROUND: Although psychosocial distress has been evaluated well in cancer entities like breast or prostate cancer, its impact on melanoma patients still needs to be characterized. The objectives of this study were to (i) evaluate psychosocial distress in melanoma patients using an expert rating instrument [basic documentation for psycho-oncology short version (PO-Bado SF)]; (ii) determine associated demographic and clinical variables; and (iii) assess the acceptance of using PO-Bado SF as a routine procedure in a skin cancer unit. METHODS: A cross-sectional group of 696 melanoma patients was recruited. During the routine contact, doctors assessed the patients subjective distress using PO-Bado SF. Sociodemographic data, tumour data, treatment and the course of the disease were extracted from the patients' charts. RESULTS: PO-Bado SF was completed in 688 of 696 (99%) participating patients, revealing a high acceptance. In 51 (7%) patients, the PO-Bado SF cut-off score indicated the potential need of psychosocial support. Patients with previous or ongoing radiotherapy, a history of major surgery due to organ metastases, younger age and shorter time since diagnosis were considered significantly more distressed than patients without these criteria. Patients were most distressed by suffering from anxiety/worries and/or tensions. In younger patients emotional variables and other problems like social or family problems were deemed more relevant while functional limitations in daily living were reasons for higher distress in older patients. CONCLUSION: PO-Bado SF is a useful, well-accepted, practical and economic screening tool to identify distressed melanoma patients. Although most melanoma patients seem to cope well with their disease, special attention should be given to young patients in the first years after initial diagnosis and to patients with advanced disease, radiotherapy and major surgery due to their disease. Combination of expert rating tools with self-report screening instruments could further characterize the specific sources of distress to optimize psychosocial support.

[Phlebology in German departments of dermatology. An analysis on behalf of the German Society of Phlebology]. / Phlebologie an deutschen Hautkliniken. Eine Bestandsaufnahme im Auftrag der Deutschen Gesellschaft für Phlebologie.

BACKGROUND: Phlebologic diseases have become extremely common and have major socio-economic impact. However, the percentage of dermatologists working in phlebology appears to be decreasing according to the data of the German Society of Phlebology (DGP). METHODS: To investigate the reasons for this development, we--on behalf of the DGP--sent a questionnaire to 120 German Departments of Dermatology in autumn 2012. RESULTS: In 76 returned questionnaires, the number of physicians with additional fellowship training in phlebology averaged 1.5; the average number of those who fulfill the criteria for training fellows in phlebology was 0.9. In 71.1 % of the departments there was a phlebologist. A special phlebologic outpatient clinic existed in 73.7 % of the departments. Sonography with Doppler (89.5 %) and duplex (86.8 %) was used as the most frequent diagnostic tool. For therapy, compression (94.7 %), sclerotherapy (liquid 78.9 %, foam 63.2 %, catheter 18.4 %), endoluminal thermic procedures (radio wave 28.9 %, laser 17.1 %) and surgery (especially crossectomy and stripping 67.1 %, phlebectomy of tributaries 75 %) were used. The average number of treatments was very heterogenous in the different departments. CONCLUSIONS: Phlebology definitely plays an important role in dermatology. Most departments fulfill the formal criteria for the license to conduct advanced training in phlebology. A wide spectrum of phlebological diagnostic and therapeutic procedures is available.

Self-management-competency as a new target in Hidradenitis suppurativa care.

Background: Hidradenitis suppurativa affects approximately 1% of the population.Objective: Highlighting the relevance of self-management-competency as a new therapeutic target.Method: 258 patients from the 'Epidemiology and Care in Acne inversa (EpiCAi)' project were included in the study. Disease burden was measured by patient-rated questionnaires in terms of disease activity, pain, quality of life, depression and insomnia and correlated with the domains of the health education impact questionnaire (heiQ) measuring self-management-competency.Results: 66 male (25.6%) and 192 female (74.4%) patients, with a mean age of 40.3 ± 10.24 years were included. Mean scores of pain on the numeric rating scale (NRS), Dermatology Life Quality Index (DLQI) and Hospital Anxiety and Depression Scale (HADS) were 5.11 ± 2.68, 11.35 ± 7.79 and 13.71 ± 7.57, respectively. The Insomnia severity index (ISI) showed a mean of 9.58 ± 5.76. The HADS has the highest increased total risk across all heiQ domains. With respect to the heiQ domains, the highest exposure can be attributed to improving constructive attitudes and approaches as well as decreasing emotional distress.Conclusion: There is a clear association of self-management-competency with overall disease burden, which underlines the need for psychoeducational support. This study provides ideas to develop new possible strategies of care.

Gram-positive bacteria on grass pollen exhibit adjuvant activity inducing inflammatory T cell responses.

BACKGROUND: Recently, it has been established that pollen grains contain Th2-enhancing activities besides allergens. OBJECTIVE: The aim of this study was to analyse whether pollen carry additional adjuvant factors like microbes and what immunological effects they may exert. METHODS: Timothy pollen grains were collected and disseminated on agar plates, and the growing microorganisms were cultivated and defined. Furthermore, the immunologic effects of microbial products on DC and T cell responses were analysed. RESULTS: A complex mixture of bacteria and moulds was detected on grass pollen. Besides Gram-negative bacteria that are known to favour Th1-directed immune responses, moulds were identified as being sources of allergens themselves. Herein, we focused on Gram-positive bacteria that were found in high numbers, e.g. Bacillus cereus and Bacillus subtilis. Contact of immature dendritic cells (DC) from grass pollen allergic donors with supernatants of homogenized Gram-positive bacteria induced maturation of DC as measured by up-regulation of CD80, CD83 and CD86 and by enhanced production of IL-6, IL-12p40 and TNF-α, which was less pronounced compared with effects induced by lipopolysaccharide (LPS). Consequently, stimulation of autologous CD4(+) T cells with supernatants of homogenized Gram-positive bacteria plus grass pollen allergen-pulsed DC led to an enhanced proliferation and production of IL-4, IL-13, IL-10, IL-17, IL-22 and IFN-γ production compared with T cells that were stimulated with allergen-pulsed immature DC alone, whereas production of the transcription factor for regulatory T cells FoxP3 was not significantly affected. CONCLUSIONS AND CLINICAL RELEVANCE: These data indicate that grass pollen is colonized by several microorganisms that influence the immune response differently. Similar to LPS, supernatants of homogenized Gram-positive bacteria may serve as adjuvants by augmenting DC maturation and inflammatory Th1, Th2 and Th17 responses helping to initiate allergic immune responses.

[Systemic therapy for malignant melanoma]. / Medikamentöse Therapie des malignen Melanoms.

For decades dacarbazine was the standard in the therapy for metastatic melanoma even though response rates were low. In recent years multiple pharmacological approaches have led to new therapy options including immune modulators like anti-CTLA4 antibodies and kinase inhibitors of the MAPK signaling pathway that showed better response rates and increased overall survival. However, since immune modulators lead only in a small subgroup of patients to long-term responses and kinase inhibitors lose their function due to development of resistance after several months, continuation of clinical studies is strongly required. Classical chemotherapeutic drugs will remain a basic part of the therapy especially as combinations of different treatment options have to be focused on in order to achieve better long-term survival rates.

Vaccination of melanoma patients with peptide- or tumor lysate-pulsed dendritic cells.

Melanoma is the main cause of death in patients with skin cancer. Cytotoxic T lymphocytes (CTLs) attack melanoma cells in an HLA-restricted and tumor antigen-specific manner. Several melanoma-associated tumor antigens have been identified. These antigens are suitable candidates for a vaccination therapy of melanoma. Dendritic cells (DCs) are antigen-presenting cells (APCs) specialized for the induction of a primary T-cell response. Mouse studies have demonstrated the potent capacity of DCs to induce antitumor immunity. In the present clinical pilot study, DCs were generated in the presence of granulocyte/macrophage-colony stimulating factor (GM-CSF) and interleukin 4 (IL-4) and were pulsed with tumor lysate or a cocktail of peptides known to be recognized by CTLs, depending on the patient's HLA haplotype. Keyhole limpet hemocyanin (KLH) was added as a CD4 helper antigen and immunological tracer molecule. Sixteen patients with advanced melanoma were immunized on an outpatient basis. Vaccination was well tolerated. No physical sign of autoimmunity was detected in any of the patients. DC vaccination induced delayed-type hypersensitivity (DTH) reactivity toward KLH in all patients, as well as a positive DTH reaction to peptide-pulsed DCs in 11 patients. Recruitment of peptide-specific CTLs to the DTH challenge site was also demonstrated. Therefore, antigen-specific immunity was induced during DC vaccination. Objective responses were evident in 5 out of 16 evaluated patients (two complete responses, three partial responses) with regression of metastases in various organs (skin, soft tissue, lung, pancreas) and one additional minor response. These data indicate that vaccination with autologous DCs generated from peripheral blood is a safe and promising approach in the treatment of metastatic melanoma. Further studies are necessary to demonstrate clinical effectiveness and impact on the survival of melanoma patients.

Overexpression of CD40 ligand in murine epidermis results in chronic skin inflammation and systemic autoimmunity.

CD40-CD40 ligand (L) interactions play a pivotal role in immune-mediated inflammatory responses via the activation of antigen-presenting cells (APCs). To investigate the effects of continuous activation of resident tissue APCs, in this case the Langerhans cells (LCs) of the skin, CD40L expression was targeted to the basal keratinocytes of the epidermis of mice using the keratin-14 promoter. Approximately 80% of the transgenic (Tg) mice spontaneously developed dermatitis on the ears, face, tail, and/or paws. Compared with littermates, Tgs had a >90% decrease in epidermal LCs yet increased numbers within the dermis suggestive of enhanced emigration of CD40-activated LCs. Tgs also displayed massive regional lymphadenopathy with increased numbers of dendritic cells and B cells. Moreover, a decrease in IgM and an increase in IgG1/IgG2a/IgG2b/IgE serum concentrations was detectable. Screening for autoantibodies revealed the presence of antinuclear antibodies and anti-dsDNA antibodies implicative of systemic autoimmunity. Accordingly, renal Ig deposits, proteinuria, and lung fibrosis were observed. Adoptive transfer of T cells from Tgs to nonTg recipients evoked the development of skin lesions similar to those found in the Tgs. Dermatitis also developed in B cell-deficient CD40L Tg mice. These findings suggest that in situ activation of LCs by CD40L in the skin not only leads to chronic inflammatory dermatitis but also to systemic mixed-connective-tissue-like autoimmune disorders, possibly by breaking immune tolerance against the skin.

Interaction of dendritic cells with skin endothelium: A new perspective on immunosurveillance.

The goal of this study was to determine the mechanisms by which dendritic cells (DCs) in blood could interact with endothelium, a prerequisite to extravasation into tissues. Our results indicate that DCs express both HECA-452-reactive and nonreactive isoforms of P-selectin glycoprotein ligand 1 (PSGL-1) and can tether and roll efficiently on E- and P-selectin under flow conditions in vitro. Freshly isolated blood DCs were further observed to roll continuously along noninflamed murine dermal endothelium in vivo. This interaction is strictly dependent on endothelial selectins, as shown by experiments with blocking antibodies and with E- and P-selectin-deficient mice. We hypothesize that DCs in blood are constitutively poised at the interface of blood and skin, ready to extravasate upon induction of inflammation, and we showed that cutaneous inflammation results in a rapid recruitment of DCs from the blood to tissues. We propose that this is an important and previously unappreciated element of immunosurveillance.

Spontaneous skin ulceration and defective T cell function in CD18 null mice.

A null mutation was prepared in the mouse for CD18, the beta2 subunit of leukocyte integrins. Homozygous CD18 null mice develop chronic dermatitis with extensive facial and submandibular erosions. The phenotype includes elevated neutrophil counts, increased immunoglobulin levels, lymphadenopathy, splenomegaly, and abundant plasma cells in skin, lymph nodes, gut, and kidney. Very few neutrophils were found in spontaneously occurring skin lesions or with an induced toxic dermatitis. Intravital microscopy in CD18 null mice revealed a lack of firm neutrophil attachment to venules in the cremaster muscle in response to N-formyl- methionyl-leucyl-phenylalanine. A severe defect in T cell proliferation was found in the CD18 null mice when T cell receptors were stimulated either by staphylococcal enterotoxin A or by major histocompatibility complex alloantigens demonstrating a greater role of CD11/CD18 integrins in T cell responses than previously documented. The null mice are useful for delineating the functions of CD18 in vivo.

Antigen dose-dependent suppression of murine IgE responses is mediated by CD4(-)CD8(-) double-negative T cells.

BACKGROUND: The IgE response against protein antigens is profoundly influenced by the dose used for sensitization. OBJECTIVE: The aim of the study was to identify immune cells that are involved in antigen dose-dependent regulation of IgE formation. METHODS: Wild-type mice as well as T helper (Th)1-deficient IL-12p40(-/-) and IFN-gamma(-/-) mice were immunized by repeated intraperitoneal injection of either low doses (K01 mice) or high doses (K100 mice) of keyhole limpet haemocyanin adsorbed to aluminium hydroxide. Splenocytes of immunized mice were restimulated in vitro and antigen-dependent T cell proliferation and cytokine production were measured. The frequency of regulatory T cell subsets among splenocytes from K01 and K100 mice was compared using fluorocytometry and RT-PCR analysis. Splenocytes or T cell subpopulations were transferred into naïve mice and the effect of lymphocyte transfer on IgE production after priming of recipients with low antigen doses was determined. RESULTS: Specific IgE production was considerably impaired in K100 mice. Antigenic restimulation revealed hypoproliferation of K100 splenocytes and reduced production of Th2 cytokines IL-4, IL-5 and IL-13, but no induction of IFN-gamma production. Moreover, lymphocytes from K01 and K100 mice did not show significant differences in the expression of molecules associated with the phenotype or activity of conventional regulatory T cells. Transfer of splenocytes or purified T cells from K100 mice substantially suppressed the induction of IgE production in the recipients in an antigen- and isotype-specific manner. Neither CD4(+) nor CD8(+) T cells from K100 mice were able to inhibit IgE formation; instead, we identified CD4(-)CD8(-) double-negative T cells (dnT cells) as the principal T cell population, which potently suppressed IgE production. CONCLUSION: Our data demonstrate that CD4(-)CD8(-) dnT cells play a major role in the regulation of IgE responses induced by high antigen doses.

Vacuum assisted closure device improves the take of mesh grafts in chronic leg ulcer patients.

BACKGROUND: Vacuum assisted closure (VAC) is established in the management of acute and chronic wounds. In recent years, few data have been published concerning VAC therapy after skin graft transplantation. OBJECTIVES: The aim of this study was to determine whether postoperative VAC helps assist closure of mesh grafts in chronic leg ulcer patients. PATIENTS/METHODS: We report a consecutive case series of 54 patients with chronic leg ulcers who received a total of 74 mesh grafts. A postoperative VAC therapy was performed in 28 mesh grafts, and 46 mesh grafts were treated with standard gauze therapy. RESULTS: In the VAC group, 92.9% of grafts showed complete healing, compared to 67.4% in the control group without postoperative VAC therapy. Differential analysis revealed a negative correlation of the take rate in patients over 70 years of age or in patients suffering from diabetes mellitus or dermatoliposclerosis. Particularly patients with diabetes mellitus and of greater age exhibited improved take rates, both 100%, in the VAC group compared to 50 and 62%, respectively. CONCLUSION: The results of our retrospective study demonstrate for the first time the significant benefit of VAC therapy after skin grafting in chronic leg ulcer patients as evaluated in a clinical trial.

Insufficient tetanus vaccination status in patients with chronic leg ulcers. Results of a prospective investigation in 100 patients.

BACKGROUND: Tetanus disease is caused by Clostridium tetani and is one of the most common infectious diseases worldwide. Despite international recommendations for patients with a chronic leg ulcer, there has been a distinctive lack of protection provided by vaccination for these patients in the past decades. METHODS: Within the context of our prospective clinical investigation we consecutively determined the concentrations of immunoglobulin G antibodies against C. tetani in 100 patients with a chronic leg ulcer between January 2005 and November 2006. RESULTS: A total of 38 patients were male, and 62 were female. Their mean age was 71 years (25-94). In a total of 47% (n = 47; 13 male, 34 female, mean age: 76 years) of the patients, insufficient immunoglobulin G antibody concentrations were detected. Particularly the subanalysis indicated an insufficient tetanus protection provided by vaccination in 70% of the people aged >or=80 years. CONCLUSION: A chronic wound, e.g. in the form of a leg ulcer, is known as a potential entrance for C. tetani. Unlike acute wounds, however, it is hardly ever considered to be a reason for assessment of the tetanus immune status. The results of our investigation clarify that particularly elderly people suffering from a leg ulcer have to be tested for tetanus protection provided by vaccination more strictly than ever, and if necessary, vaccinations have to be renewed.

Contact sensitization in patients with chronic wounds: results of a prospective investigation.

BACKGROUND: It is well known that patients with chronic wounds frequently acquire clinically relevant contact sensitizations to skin care products. OBJECTIVES: The aim of our study was to find out the actual frequency of contact sensitivities in patients with chronic wounds in Germany with particular attention to components of products used in modern wound therapy. METHODS: We examined the results of a prospective clinical investigation on skin patch tests of patients with chronic wounds. RESULTS: Altogether, 45 patients with chronic wounds were tested. In 25 (55.5%) of the examined patients, contact sensitization to at least one substance was detected. The most frequent contact sensitizations were to PVP-iodine (20%), balsam of Peru (15.6%) patients, fragrance mix (11.1%), colophony (8.8%) and potassium dichromate (6.7%). We also found sensitization to the wound dressings Varihesive (11.1%), Iruxol N (6.7%) and Comfeel (2.2%). CONCLUSIONS: We would like to propagate that therapists who are involved in wound treatment should also pay attention on the ingredients of applied modern wound dressings.

[Keratosis follicularis spinulosa decalvans]. / Keratosis follicularis spinulosa decalvans.

Keratosis follicularis spinulosa decalvans is a rare, X-linked disorder of keratinization of the hair follicle with inflammation and atrophy associated with corneal dystrophy and other symptoms. A family with several affected members is reported. The unaffected parents were related. A 12-year-old girl and her 5-year-old brother had follicular spiny hyperkeratoses on the trunk and extremities. The girl had thinning of the eyelashes and eyebrows as well as scarring alopecia of the scalp as additional features of the disease. Both the girl and her brother had corneal dystrophy and photophobia. Two sisters aged 8 and 10 years did not show similar skin or eye findings.