ABSTRACT
BACKGROUND: Myotonic dystrophy type 1 (MD1) is reported to be associated with internal malignancies. The association of myotonic dystrophy with cutaneous tumors is not fully understood. OBJECTIVE: We sought to explore the total nevi count and the presence of atypical nevi, cutaneous melanoma, and other skin neoplasms in a representative cohort of patients with MD1 and to compare the findings with age- and sex-matched control subjects. METHODS: In all, 90 patients with MD1 and 103 age- and sex-matched control subjects were assessed for cutaneous neoplasms by clinical skin and epiluminescence examination (dermoscopy). Where indicated, subsequent excisions were performed. In patients with MD1, leukocyte n(CTG) expansion was measured. RESULTS: Patients with MD1 showed significantly higher numbers of nevi, dysplastic nevi, and melanomas despite a significantly greater proportion of the control subjects reporting sunburns. In addition, we found a significantly greater number of pilomatrixoma in patients with MD1. LIMITATIONS: Our study is limited by the fact that there is no agreed-upon standardized technique to assess for prior sun exposure. Further research in the association of cutaneous neoplasms and MD1 including vitamin D and molecular biological techniques are also recommended. CONCLUSION: MD1 itself may predispose to development of skin tumors.
Subject(s)
Dysplastic Nevus Syndrome/complications , Dysplastic Nevus Syndrome/epidemiology , Melanoma/complications , Melanoma/epidemiology , Myotonic Dystrophy/complications , Skin Neoplasms/complications , Skin Neoplasms/epidemiology , Adolescent , Adult , Aged , Aged, 80 and over , Cross-Sectional Studies , Female , Humans , Male , Middle Aged , Prevalence , Young AdultABSTRACT
INTRODUCTION: Fabry disease is an X-linked inherited metabolic disorder characterized by the deficiency of lysosomal α-galactosidase A enzyme. This leads to the accumulation, into lysosomes through the body, of glycosphingolipids, mainly Gb3. Skin involvement and progressive multi-organ failure are usually observed. Endothelium is the preferential target of the Gb3 storage that determines endothelial dysfunction and vasculopathy leading to the clinical manifestations of the disease. The serum levels of Vascular Endothelial Growth Factor-A (VEGF-A), a specific endothelial cell mitogen, were analyzed in Fabry patients to explore a possible association to the clinical manifestations with vascular involvement. METHODS: Thirty-five patients with a biochemical and genetic diagnosis of Fabry disease, along with an age-gender-matched healthy control group, were enrolled. Serum samples were collected and analyzed by ELISA. The genetic mutations, the specific organ dysfunction, and the cardiovascular risk factors such as dyslipidaemia, diabetes, smoking habits and hypertension were evaluated in Fabry patients. RESULTS: The mean serum level of VEGF-A in Fabry patients group was significantly higher than in the control group (P=0.006). A statistical significant association, between VEGF-A levels and the skin manifestation including angiokeratomas, sweating abnormalities and Fabry Facies was found. An association was also found between high VEGF-A and specific GLA mutations, the male gender, the renal and neurological manifestations, the presence of eye vessels tortuosity, smoking habit and hypertension. CONCLUSIONS: We detected increased VEGF-A levels in patients with Fabry disease compared to the controls, and we hypothesized that this could be a response to the vascular damage characterising this lysosomal disorder. However, further studies are necessary to clarify the role of VEGF-A in Fabry.
Subject(s)
Blood Vessels/pathology , Fabry Disease/blood , Skin/pathology , Vascular Endothelial Growth Factor A/blood , Adolescent , Adult , Aged , Case-Control Studies , Child , Child, Preschool , Fabry Disease/enzymology , Fabry Disease/genetics , Fabry Disease/therapy , Female , Humans , Male , Middle Aged , Mutation/genetics , Organ Specificity , Young Adult , alpha-Galactosidase/geneticsABSTRACT
BACKGROUND: Although the majority of skin cancers in albino patients consists of squamous and basal cell carcinomas, malignant melanomas have also been described, albeit less frequently. OBJECTIVE: The aim of our study was to evaluate melanocytic lesions in albino patients to look for any recurrent dermoscopic pattern. METHODS: We enrolled 12 consecutive albino patients presenting to our department and examined each patient for the presence of melanocytic nevi with the unaided eye and then with dermoscopy. Melanocytic lesions with suspicious clinical or dermoscopic features were excised and histopathologically evaluated. RESULTS: Analysis of the recorded images permitted us to find two main dermoscopic patterns in this group of patients. The first one was represented by a homogeneous light-brown yellowish pattern associated with comma-like and dotted vessels; the second one consisted of a classical brown reticular pattern frequently associated with central depigmentation and with comma-like vessels. Moreover, based on some atypical dermoscopic features, in 2 patients we excised 3 melanomas in situ (in the same patient) and a thick melanoma (3.2 mm). CONCLUSIONS: Dermoscopy may represent a useful tool for the evaluation of melanocytic lesions in albino patients, permitting an early diagnosis of melanoma.
Subject(s)
Albinism, Oculocutaneous/complications , Dermoscopy , Nevus, Pigmented/pathology , Skin Neoplasms/pathology , Adolescent , Adult , Child , Child, Preschool , Female , Humans , Male , Middle Aged , Nevus, Pigmented/complications , Skin Neoplasms/complicationsABSTRACT
BACKGROUND: Epidermodysplasia verruciformis (EV) is a rare genodermatosis characterized by immunologic abnormalities, disseminated human papilloma virus infection, and early development of skin cancers. Acquired forms have been rarely reported and usually occur with immunosuppression. The therapeutic management of the acquired forms is not standardized, and several therapies have been tried, with variable outcomes. OBJECTIVES: To provide updated clinical and experimental information on the treatment of acquired EV. METHODS: A Medline literature search was performed for relevant Medical Subject Heading terms, reviewing publications on strategies for management of acquired EV. We also report a case successfully treated using a combination of photodynamic therapy and oral retinoids. CONCLUSION: Data from the literature show that a standardized approach to this condition is lacking; the combination treatment chosen in our case may be proposed because it led to an excellent clinical outcome and a long-lasting remission.
Subject(s)
Aminolevulinic Acid/analogs & derivatives , Epidermodysplasia Verruciformis/therapy , Photochemotherapy , Photosensitizing Agents/administration & dosage , Retinoids/administration & dosage , Administration, Oral , Aminolevulinic Acid/administration & dosage , Combined Modality Therapy , Diathermy , Epidermodysplasia Verruciformis/immunology , Epidermodysplasia Verruciformis/pathology , Female , Humans , Immunocompromised Host , Middle Aged , Treatment OutcomeABSTRACT
PURPOSE: Ocular mucous membrane pemphigoid (OMMP) is an autoimmune disease involving the eye and characterized by subepithelial detachment resulting from an immunologic reaction against conjunctival basal membrane zone (BMZ) antigens. Lyell syndrome (LS) is a drug-induced, T cell-mediated, cytotoxic reaction involving the mucocutaneous areas. Two patients with LS are presented in whom OMMP developed. DESIGN: Report of 2 cases. PARTICIPANTS: Two male patients, 80 and 60 years old, with persistent corneal ulcerations, corneal melting, and inflammation some months after an LS episode. METHODS: Conjunctival biopsy samples were obtained to perform direct immunofluorescence (DIF) and histologic analyses. Indirect immunofluorescence (IIF) and enzyme-linked immunosorbent assay (ELISA) also were performed. MAIN OUTCOME MEASURES: Immunodeposit findings on the conjunctival BMZ obtained by DIF and IIF, inflammatory infiltration of the corneoconjunctival samples studied by histologic analysis, and autoantibodies of patient sera directed against BMZ antigens tested by ELISA. RESULTS: Direct immunofluorescence analyses showed immunoglobulin G and complement 3 component deposits along the BMZ in a linear pattern. Histologic analysis revealed the presence of eosinophils, neutrophils, and mast cells with fibrin deposition in the substantia propria of both patients; the data confirmed the clinical suspicion of OMMP. The IIF and ELISA results were negative. CONCLUSIONS: Chronic eye surface injury associated with LS may promote autoimmunization against ocular epithelial BMZ antigens, playing a strategic role in the subsequent onset of OMMP. The occurrence of OMMP after LS could be an occasional finding, or conversely, LS could be an underestimated predisposing factor in the development of OMMP.
Subject(s)
Conjunctival Diseases/etiology , Pemphigoid, Benign Mucous Membrane/etiology , Stevens-Johnson Syndrome/complications , Aged, 80 and over , Autoantibodies/blood , Autoantigens/immunology , Basement Membrane/immunology , Biopsy , Conjunctival Diseases/diagnosis , Enzyme-Linked Immunosorbent Assay , Fluorescent Antibody Technique, Direct , Fluorescent Antibody Technique, Indirect , Humans , Male , Middle Aged , Pemphigoid, Benign Mucous Membrane/diagnosis , Risk FactorsABSTRACT
An observational, questionnaire-based, cross-sectional study was performed to assess whether differences in coping behaviour (positive and negative strategies) between patients with either a recent diagnosis of malignant melanoma (MM) or with benign dermatological disease, were predictive of the diagnosis. Coping strategies were assessed with the German version of the stress-coping questionnaire (SVF 120) in 46 inpatients for whom surgery was planned at the Department of Dermatology, Medical University of Graz, Austria. Subjects were divided into two groups: patients with non-metastatic MM, and patients with benign dermatological diseases (controls). The risk for the diagnosis "melanoma" decreased with higher values of "situation control" (p = 0.007) and increased with higher values of resignation (p = 0.035) and trivialisation (p = 0.039). More-over, the risk for having a MM with thickness > 1 mm decreased in patients with higher values in positive coping strategies (p < 0.34). These results suggest differences in coping behaviour between patients with MM and those with benign skin diseases and, amidst patients with MM, between patients with different MM thickness; the results may hence lead to earlier, more specific and more effective psychological interventions to improve coping in patients with MM, as differences in coping behaviour seem to appear even in the non-metastatic stage of the disease.
Subject(s)
Adaptation, Psychological , Melanoma/psychology , Skin Neoplasms/psychology , Stress, Psychological/psychology , Adult , Case-Control Studies , Cost of Illness , Cross-Sectional Studies , Emotions , Female , Health Knowledge, Attitudes, Practice , Humans , Male , Melanoma/complications , Melanoma/pathology , Middle Aged , Pilot Projects , Quality of Life , Risk Factors , Skin Neoplasms/complications , Skin Neoplasms/pathology , Stress, Psychological/etiology , Surveys and QuestionnairesABSTRACT
AIMS: This study estimated the resource implications and budget impact of managing adults with Fabry disease in Italy, from the perspective of the Servizio Sanitario Nazionale (SSN). METHODS: A decision model was constructed using published clinical outcomes and clinician-derived resource utilisation estimates depicting the management of adults with Fabry disease in Italy. RESULTS: The expected annual cost of managing 220 existing and 20 new Fabry patients in Italy was estimated to be 28·3 million. In an average year, patients receiving enzyme replacement therapy (ERT) with 0·2 mg kg(-1) agalsidase alfa (Replagal; Shire Human Genetic Therapies, Basingstoke, Hampshire, UK) or 1·0 mg kg(-1) agalsidase beta (Fabrazyme; Genzyme Europe BV, Naarden, The Netherlands) are collectively expected to make 4500 hospital attendances to a day ward for infusions, which equates to 2000 eight-h days on the day ward associated with ERT. If all ERT-treated patients received their infusions at home, there would be a marginal reduction in the annual health care cost to manage these patients, and the total annual number of days on the day ward associated with ERT in the second year could potentially be reduced from a mean 2000 to zero, thereby releasing substantial hospital resources for use by non-Fabry patients. Currently, only agalsidase alfa is licensed for home treatment in Italy; hence, only patients receiving this enzyme could be offered home treatment. CONCLUSION: Use of agalsidase alfa (0·2 mg kg(-1) ) instead of agalsidase beta (1·0 mg kg(-1)) has the potential to reduce health care costs and release hospital resources in different specialities for alternative use by non-Fabry patients, thereby improving the efficiency of the public health care system in Italy.
Subject(s)
Fabry Disease/economics , Health Care Costs/statistics & numerical data , Models, Econometric , Adult , Decision Support Techniques , Drug Costs/statistics & numerical data , Fabry Disease/diagnosis , Fabry Disease/drug therapy , Female , Health Resources/economics , Health Resources/statistics & numerical data , Humans , Isoenzymes/economics , Isoenzymes/therapeutic use , Italy , Male , Recombinant Proteins , Sensitivity and Specificity , alpha-Galactosidase/economics , alpha-Galactosidase/therapeutic useABSTRACT
We report the case of a 13-year-old boy with an abrupt onset of leg pain and muscle weakness, incapability of deambulation and a laboratory picture of exercise-induced acute rhabdomyolysis. Intravenous hyperhydration and forced diuresis were adopted to avoid renal complications. No evidence of articular or residual muscular damage was appreciated in the short-term. The recurrence of rhabdomyolysis required a muscular biopsy showing a disturbance of fatty acid ß-oxidation pathway.
Subject(s)
Exercise , Metabolism, Inborn Errors/pathology , Mobility Limitation , Rhabdomyolysis/pathology , Adolescent , Carnitine O-Palmitoyltransferase/deficiency , Humans , Male , Metabolism, Inborn Errors/complications , Metabolism, Inborn Errors/physiopathology , Muscle Weakness/etiology , Muscle Weakness/pathology , Muscle Weakness/physiopathology , Rhabdomyolysis/etiology , Rhabdomyolysis/physiopathologyABSTRACT
Vitamin D plays an important role in maintaining the homeostasis of various biological systems. Beside its well-known function in calcium and phosphate metabolism, it plays a major role in pathophysiology of skin and adnexa. Indeed, vitamin D, through its receptor (VDR), decreases keratinocyte proliferation, improves their differentiation and modulates both cutaneous innate (antimicrobial activity and antigen presentation) and adaptative immunity (T and B lymphocyte function). The maintenance of normal hair is dependant on the integrity of the dermis, epidermis and hair cycles. Beside its effect on epidermal differentiation, VDR plays a vital role in preserving the hair follicle integrity. While the relevance of VDR has been fully elucidated, the real value of vitamin D in the hair follicle cycle still remains uncertain. To date, results in literature remain contradicting and far from definitive; still, the role of vitamin D in the various forms of human alopecia is likely to be significant. The aim of this article is to review evidence about the role of vitamin D and its receptor in trichology, with a focus on scarring and non-scarring alopecia and in particular on the potential therapeutic use of Vitamin D for hair and scalp disorders.
Subject(s)
Hair Diseases/etiology , Receptors, Calcitriol/physiology , Scalp Dermatoses/etiology , Vitamin D/physiology , Vitamins/physiology , HumansABSTRACT
Darier's disease (DD) is an autosomal dominant inherited genodermatosis which is often under- or misdiagnosed. In the majority of cases, the disease manifests in adolescents or young adults with small brownish-yellow, warty, hyperkeratotic papules in multiple seborrheic areas of the body. Localized DD (LDD) is a clinical variant, first described by Kreibich in 1906; only a few cases are reported in the literature. We described the case of an aged woman presenting with LDD, and we review the literature on this subject.
ABSTRACT
BACKGROUND: Fabry disease (FD) is an X-linked lysosomal storage disorder caused by a deficiency of alpha-galactosidase A enzyme, which leads to the accumulation of its substrate, the globotriaosylceramide or Gb3, in many organs and tissues. Main clinical manifestations of FD are neuropathic pain, angiokeratomas, proteinuria and renal failure, left ventricular hypertrophy and stroke. Fever is also a possible symptom at the onset of the disease during childhood and adolescence, but it is frequently misdiagnosed, causing a delay in FD diagnosis. METHODS: We retrospectively analysed the medical records in our series of 58 Fabry patients, focusing on the proportion of patients who exhibited fever as the main symptom at the onset of FD in order to evaluate the diagnostic delay in these patients. FINDINGS: In our series, we found a significant proportion of patients with a history of fevers at the beginning of their medical history (20.7%; 12/58). 83% of patients with fever also exhibited acroparesthesias (10/12). Inflammatory markers were elevated in few of those cases (2/12). The mean diagnostic delay was 15.6±SD 12.8years. INTERPRETATION: Fever emerged to be common as part of the FD clinical spectrum and it significantly contributed to the diagnostic delay encountered with this rare disease. Furthermore, our retrospective analysis indicated that FD patients commonly exhibit episodes of fever in association with other symptoms suggestive of FD (such as episodic pain crisis, acroparesthesias, hypo/anhydrosis, heat intolerance, fatigue and gastrointestinal distress). A careful analysis of the medical history in patients suffering fever could lead to an early and correct FD diagnosis. We believe that fever/hyperthermia, acroparesthesias and angiokeratoma should be considered for inclusion in the algorithm for Intermittent Fever of Unknown Origin (FUO) in order to improve the recognition of FD.
Subject(s)
Angiokeratoma/etiology , Fabry Disease/complications , Fever of Unknown Origin/etiology , Paresthesia/etiology , Skin Neoplasms/etiology , Child , Child, Preschool , Delayed Diagnosis , Diarrhea/etiology , Dyspepsia/etiology , Fabry Disease/diagnosis , Fatigue/etiology , Female , Humans , Hypertrophy, Left Ventricular/etiology , Hypohidrosis/etiology , Male , Retrospective StudiesSubject(s)
Carcinoma, Basal Cell/etiology , Skin Neoplasms/etiology , Abnormalities, Multiple , Carcinoma, Basal Cell/drug therapy , Carcinoma, Basal Cell/surgery , Female , Heart Defects, Congenital/complications , Heterotaxy Syndrome , Humans , Shoulder , Skin Neoplasms/drug therapy , Skin Neoplasms/surgery , Splenic Diseases/complications , Splenic Diseases/congenital , Young AdultABSTRACT
Human epidermis shows a non-neuronal cholinergic system including keratinocyte (kc) acetylcholine (Ach) axis which is composed by enzymes and two families of Ach receptors (muscarinic and nicotinic receptors). The activity of these two receptors can regulate the interkeratinocytes and kcs-extracellular matrix adhesion modifying the regulation of intercellular adhesion molecules like cadherins and integrins. Some authors demonstrate that acantholysis in pemphigus depends not only on anti desmogleins antibodies (abs) (mostly IgG) but even on other abs directed against kc membrane antigens (e.g. anti Ach receptors Abs). In the early phase of pemphigus pathogenesis, anti Ach receptors Abs block Ach signaling essential for cell shape and intercellular adhesion and increase the phosphorylation of adhesion molecules. Combined with the action of abs antidesmogleins, anti Ach receptors Abs cause the acantholytic phenomenon. In vitro experiments show that high doses of Ach in acantholytic kcs can rapidly reverse this pathologic event. In vivo experiments using neonatal mice model of Pemphigus have demonstrated that cholinergic agonists reduce these lesions. Therapy with pyridostigmine bromide and Nicotinamide per os or pilocarpine used topically, drugs that present cholinomimetic effects, has lead to encouraging results in patients affected by Pemphigus disease. Cholinergic agents could have a strategic role in the therapy of pemphigus since they could be responsible for the early stage of acantholytic diseases.
Subject(s)
Acantholysis/etiology , Cholinergic Agents/pharmacology , Keratinocytes/physiology , Pemphigus/drug therapy , Acantholysis/pathology , Acetylcholine/metabolism , Acetylcholine/physiology , Animals , Cell Adhesion/physiology , Cell Adhesion Molecules/physiology , Cell-Matrix Junctions/physiology , Epidermis/metabolism , Humans , Mice , Pemphigus/pathology , Receptors, Muscarinic/physiology , Receptors, Nicotinic/physiology , Signal Transduction/physiologySubject(s)
Fabry Disease/complications , Helicobacter Infections/etiology , Helicobacter pylori/isolation & purification , Intestinal Diseases/etiology , Intestine, Small/microbiology , Adult , Case-Control Studies , Female , Helicobacter Infections/diagnosis , Helicobacter Infections/epidemiology , Humans , Intestinal Diseases/diagnosis , Intestinal Diseases/epidemiology , Intestinal Diseases/microbiology , Male , Middle Aged , Prevalence , Prospective StudiesABSTRACT
BACKGROUND: Merkel cell carcinoma is a rare, aggressive, malignant cutaneous tumor of the elderly or immunosuppressed individuals that usually appears on sun-exposed areas of the body. Its pathogenesis is still debated, and, currently, no standardized treatment exists. OBJECTIVE: To provide a current updated review of the most relevant data concerning the pathogenesis and management of Merkel cell carcinoma. METHODS: Using relevant MeSH terms, we performed a review of the literature on these subjects from 1980 to June 2009. RESULTS AND CONCLUSION: The current management of Merkel cell carcinoma is based on surgical excision as the majority of patients present with localized disease, whereas up to 30% have regional lymph node metastases. In these cases, the best outcome is achieved with multidisciplinary management that includes radiotherapy. Chemotherapy is part of the treatment in advanced cases and is mandatory for distant metastatis. Given that a recent work showed the presence of a previously unknown polyomavirus, which the authors called Merkel cell polyomavirus, the therapeutical approach to Merkel cell carcinoma could be reconsidered in the future.
Subject(s)
Carcinoma, Merkel Cell/surgery , Skin Neoplasms/surgery , Algorithms , Carcinoma, Merkel Cell/diagnosis , Carcinoma, Merkel Cell/pathology , Combined Modality Therapy , Humans , Lymph Node Excision , Neoplasm Staging , Prognosis , Sentinel Lymph Node Biopsy , Skin Neoplasms/diagnosis , Skin Neoplasms/pathologySubject(s)
Anti-Inflammatory Agents/therapeutic use , Betamethasone/analogs & derivatives , Calcitriol/analogs & derivatives , Dermatologic Agents/therapeutic use , Immunosuppressive Agents/therapeutic use , Scalp Dermatoses/drug therapy , Tacrolimus/therapeutic use , Aged, 80 and over , Betamethasone/therapeutic use , Calcitriol/therapeutic use , Drug Combinations , Female , Humans , OintmentsABSTRACT
In the absence of any other lesions on the body, the diagnosis of localized genital psoriasis can be difficult, requiring further examinations including a biopsy. We report a case of psoriatic pseudobalanitis circinata triggered by a herpes virus infection, and we discuss the Koebner phenomenon and the therapeutic management of psoriasis of the genital area.
ABSTRACT
The aim of this study is to describe by video-nailfold capillaroscopy the microvascular involvement and capillary changes in children with Henoch-Schönlein purpura (HSp) and to establish a possible correlation with clinical outcome. Thirty-one patients underwent capillaroscopic evaluation through a videomicroscope during the acute phase and after 6 months. Twenty sex/age-matched controls were also examined. All capillaroscopic variables were statistically examined in combination with laboratoristic/clinical data. Architectural and morphological changes recorded during the acute phase were statistically significant in comparison to the controls (p < 0.01). At the follow-up, oedema was still observed in all patients, whereas, morphological changes only in two. There was a no significant correlation between capillaroscopy changes, laboratoristic/clinical data, and outcome. Video-nailfold capillaroscopy can be a simple tool to evaluate microvascular abnormalities in the acute phase of HSp, and the persistence of oedema could suggest an incomplete disease resolution at a microvascular level.