ABSTRACT
Cutaneous leishmaniasis is usually easy to recognize; however, several atypical features exist, which may pose a diagnostic challenge. Here we report a 55-year-old female patient, who presented with an itchy and painful eruption localized in a dermatomal distribution along the right upper chest. Although the clinical appearance of the lesions suggested the diagnosis of herpes zoster, dermoscopic evaluation revealed erythema, hyperkeratosis, burst star whitish appearance and hairpin vessels, compatible with the diagnosis of cutaneous leishmaniasis. Indeed, leishmania amastigotes were detected by smear from the lesions. Zosteriform presentation of cutaneous leishmaniasis, as exemplified by our patient, is especially rare. In our case dermoscopy has proven to be an accessible and easy tool to diagnose such atypical presentation of cutaneous leishmaniasis, and dermatologists in endemic areas should be familiar with its typical dermoscopic features.
ABSTRACT
BACKGROUND: The combination of palmoplantar keratoderma and woolly hair is uncommon and reported as part of Naxos and Carvajal syndromes, both caused by mutations in desmosomal proteins and associated with cardiomyopathy. We describe two large consanguineous families with autosomal-recessive palmoplantar keratoderma and woolly hair, without cardiomyopathy and with no mutations in any known culprit gene. The aim of this study was to find the mutated gene in these families. METHODS AND RESULTS: Using whole-exome sequencing, we identified a homozygous missense c.2009C>T mutation in KANK2 in the patients (p.Ala670Val). KANK2 encodes the steroid receptor coactivator (SRC)-interacting protein (SIP), an ankyrin repeat containing protein, which sequesters SRCs in the cytoplasm and controls transcription activation of steroid receptors, among others, also of the vitamin D receptor (VDR). The mutation in KANK2 is predicted to abolish the sequestering abilities of SIP. Indeed, vitamin D-induced transactivation was increased in patient's keratinocytes. Furthermore, SRC-2 and SRC-3, coactivators of VDR and important components of epidermal differentiation, are localised to the nucleus of epidermal basal cells in patients, in contrast to the cytoplasmic distribution in the heterozygous control. CONCLUSIONS: These findings provide evidence that keratoderma and woolly hair can be caused by a non-desmosomal mechanism and further underline the importance of VDR for normal hair and skin phenotypes.
Subject(s)
Carrier Proteins/genetics , Hair Diseases/congenital , Keratoderma, Palmoplantar/genetics , Mutation , Tumor Suppressor Proteins/genetics , Ankyrin Repeat/genetics , Apoptosis Regulatory Proteins , Biopsy, Needle , Carrier Proteins/chemistry , Computer Simulation , DNA Mutational Analysis , Female , Hair Diseases/genetics , Humans , Intracellular Space , Keratinocytes , Male , Nuclear Receptor Coactivator 2/chemistry , Nuclear Receptor Coactivator 3/chemistry , Pedigree , Receptors, Steroid , Skin/cytology , Skin/pathology , Tumor Suppressor Proteins/chemistryABSTRACT
Iron-associated oxidative injury plays a role in retinal degeneration such as age-related macular degeneration and retinitis pigmentosa. The metallo-complex zinc-desferrioxamine (Zn/DFO) may ameliorate such injury by chelation of labile iron in combination with release of zinc. We explored whether Zn/DFO can affect the course of retinal degeneration in the rd10 mouse model of retinitis pigmentosa. Zn/DFO-treated animals showed significantly higher electroretinographic responses at 3 and 4.5 weeks of age compared with saline-injected controls. Corresponding retinal (photoreceptor) structural rescue was observed by quantitative histological and immunohistochemical techniques. When administered alone, the components of the complex, Zn and DFO, showed a lesser, partial effect. TBARS, a marker of lipid peroxidation, and levels of oxidative DNA damage as quantified by 8-OHdG immunostaining were significantly lower in Zn/DFO-treated retinas compared with saline-injected controls. Reduced levels of retinal ferritin as well as reduced iron content within ferritin molecules were measured in Zn/DFO-treated retinas. The data, taken together, suggest that the protective effects of the Zn/DFO complex are mediated through modulation of iron bioavailability, leading to attenuation of oxidative injury. Reducing iron-associated oxidative stress using complexes such as Zn/DFO may serve as a "common pathway" therapeutic approach to attenuate injury in retinal degeneration.
