Atypical Congenital Triangular Alopecia (Brauer Nevus): Case Report and Review of Literature in Occipital and Mid-Frontal Localizations.

INTRODUCTION: Brauer nevus, also known as congenital triangular alopecia (CTA) is a localized alopecia that rarely affects the occipital or mid-frontal region. CTA is a localized follicular hypoplasia, commonly misdiagnosed as alopecia areata. Although named congenital, onset in adulthood is possible. CASE PRESENTATION: We present a review of literature of eighteen atypical locations, providing 4 new cases to the 9 previously published, with particular attention to trichoscopy and histopathological descriptions in this exceptional presentation forms. DISCUSSION: Occipital and mid-frontal Brauer nevus are unusual findings with very few cases reported so far. Because of its rarity and atypical presentation, it can often lead to a misdiagnosis. A higher incidence in the male sex stands clear in these locations. Detection at birth is slightly more frequent than in the classical CTA. Histopathological and trichoscopy findings do not differ from the classical entity, although white or hypopigmented hairs do not seem to be an item present in the mid-frontal forms.

Multiple primary melanoma with the Meyerson phenomenon in a young patient.

Meyerson phenomenon (MP), also called halo eczema or halo dermatitis, was first described in 1971 as a symmetric eczematous halo around acquired melanocytic nevi. Since then, cases of MP have been described in any kind of melanocytic nevi and also in non-melanocytic tumors. To the best of our knowledge, only four cases of melanoma associated with MP have been reported. We report the singular case of a young adult diagnosed with two primary melanomas in the context of dysplastic nevi syndrome who presented several flares-up associated with MP in both benign and malignant melanocytic tumors. MP usually manifests as a halo of erythema and scaling similar to plaques of eczema symmetrically surrounding a central cutaneous tumor. Dermoscopic findings of MP show it as similar to other forms of dermatitis. Histopathology usually shows epidermal changes compatible with subacute eczematous dermatitis. Immunohistochemical studies have shown inflammatory infiltrate composed mainly of CD4+ lymphocytes, which supports the suggested pathogenesis of an immune-mediated reaction. It usually resolves spontaneously, and the use of topical corticosteroids has a good response. In conclusion, MP is not specific for benignity, even when multiple simultaneous lesions are affected. Inflammatory changes can make melanocytic lesions difficult to interpret, both on dermoscopic regression features and on histopathologic examination. Therefore, it is recommended to consider the complete excision of melanocytic lesions with atypical vessels and/or extensive regression phenomena more than 50%. Further studies are needed to know whether the presence of a melanoma could induce a remote immune response in other benign melanocytic lesions.

Nuchal Nevus Flammeus and Alopecia Areata: When Size Matters.

INTRODUCTION: Alopecia areata (AA) is a high-prevalence immuno-mediated hair loss disorder. Extra follicular affections, including nail and ocular abnormalities, are classically related to a worse prognosis of the disease, and previous studies have suggested that the presence of a persistent nuchal nevus flammeus (NNF) also indicates a greater severity and duration of the disease. The association between AA and persistent NNF was first described by Hatzis et al in 1988, who demonstrated that the relation was statistically evident and not due to a simple observer bias. OBJECTIVES: To determine and compare the presence/absence and size of the NNF in 80 individuals (40 patients diagnosed with AA and 40 controls). RESULTS: We found a statistically significant association not only between AA and the presence of NNF, but also with its size. Moreover, we found that the size of the NNF was also associated with the severity of AA. CONCLUSION: The size of the NNF in AA patients might be a useful marker of widespread and chronic disease.

Alopecic and aseptic nodule of the scalp in a girl.

Alopecic and aseptic nodule of the scalp is a rare entity characterized by the presence of nodules or cysts with sterile punctured material and negative cultures accompanied by nonscarring alopecia in the scalp of young men. We describe a case in which an 11-year-old girl presented with a nodular, fluctuant, round lesion on the vertex with localized alopecia. High-resolution ultrasound showed a hypoechoic lesion with increased flow on Doppler imaging and culture of the citrine-yellowish material obtained by puncture was negative. The patient showed complete clinical response to treatment with topical indomethacin.

Primary Scarring Alopecia: Clinical-Pathological Review of 72 Cases and Review of the Literature.

PURPOSE OF THE STUDY: To analyze the epidemiologic, demographic, clinical, and histological characteristics of primary scarring alopecia (PSA) cases diagnosed over a 7-year period at the Department of Dermatology, Hospital Clinic, Barcelona, Spain. PROCEDURES: Seventy-two patients diagnosed with PSA between 2006 and 2012 were included. Age, sex, ethnic group, clinical pattern, predominant histological infiltrate, final clinical diagnosis, time of onset, treatments used, and clinical evolution were evaluated and correlated. RESULTS: The ethnic groups were distributed as follows: 93% European-Caucasian, 5% Mestizo-American, 1% oriental, and 1% Afro-American. Most cases were females (71%), and mean age was 51 ± 6 years. The follicular pattern was the most common, and the predominant inflammatory infiltrate was lymphocytic. Lichen planopilaris and frontal fibrosing alopecia were the main diagnoses. When correlating clinical aspects and histopathology, lymphocytic PSAs had a subacute onset and resulted in a nonchanging, more stable form, while neutrophilic PSAs had a more acute onset with an evolution of acute outbreaks. PSAs in a late stage with an absent/mild infiltrate had a subclinical onset and a slowly progressive or stable evolution. CONCLUSIONS: The PSAs are severe trichological conditions. Their high clinical and histopathological variability make them a diagnostic and therapeutic challenge. MESSAGE OF THE PAPER: Knowing the clinical and histopathological aspects of PSAs should be of crucial importance to the dermatologist.

The effects of liver impairment on the pharmacokinetics of brivanib, a dual inhibitor of fibroblast growth factor receptor and vascular endothelial growth factor receptor tyrosine kinases.

PURPOSE: Hepatic impairment may impede tyrosine kinase inhibitor metabolism. This phase I study compared the pharmacokinetics of brivanib in patients with hepatocellular carcinoma (HCC) and varying levels of hepatic impairment with those with non-HCC malignancies and normal liver function. METHODS: Patients were assigned to the following groups: Groups A, B, and C (HCC plus mild, moderate, or severe hepatic impairment, respectively) and Group D (non-HCC malignancy and normal hepatic function). Brivanib alaninate (brivanib prodrug) doses were 400 mg in Groups A, B, and D and 200 mg in Group C. Brivanib exposure was determined on day 1 (single dose) and day 28 (multiple doses). RESULTS: Twenty-four patients participated in the study. After a single brivanib alaninate dose, brivanib exposure was comparable between Groups A, B, and D. Area under the concentration-time curve was 50 % higher in Group C versus Group D. There were not enough data to draw conclusions on multiple doses. Safety profile in Groups A, B, and D was consistent with previous brivanib monotherapy experience. Tolerability could not be assessed in Group C because of dose interruptions and discontinuations, generally due to the disease natural history. CONCLUSIONS: Brivanib exposure was similar in patients with HCC and mild or moderate hepatic impairment (Child-Pugh [CP] A or B status) and those with non-HCC malignancies and normal hepatic function, suggesting dose adjustment is unnecessary with CP A or B status. Experience with HCC and severe hepatic impairment (CP C status) is insufficient to recommend brivanib use in this population.

Radiobiological comparison of two radiotherapy treatment techniques for high-risk prostate cancer.

BACKGROUND: To make a radiobiological comparison, for high risk prostate cancer (T3a, PSA > 20 ng/ml or Gleason > 7) of two radiotherapy treatment techniques. One technique consists of a treatment in three phases of the pelvic nodes, vesicles and prostate using a conventional fractionation scheme of 2 Gy/fraction (SIMRT). The other technique consists of a treatment in two phases that gives simultaneously different dose levels in each phase, 2 Gy/fraction, 2.25 Gy/fraction and 2.5 Gy/fraction to the pelvic nodes, vesicles and prostate, respectively (SIBIMRT). MATERIALS AND METHODS: The equivalent dose at fractionation of 2 Gy (EQD2), calculated using the linear quadratic model with α/ß prostate = 1.5 Gy, was the same for both treatment strategies. For comparison the parameters employed were D95, mean dose and Tumour Control Probabilities for prostate PTV and D15, D25, D35, D50, mean dose and Normal Tissue Complication Probabilities for the rectum and bladder, with physical doses converted to EQD2. Parameters were obtained for α/ß prostate = 1.5, 3 and 10 Gy and for α/ß oar = 1, 2, 3, 4, 6 and 8. RESULTS: For prostate PTV, both treatment strategies are equivalent for α/ß prostate = 1.5 Gy but for higher α/ß prostate, EQD2 and TCP, decrease for the SIBIMRT technique. For the rectum and bladder when α/ß oar ≤ 2 Gy, EQD2 and NTCP are lower for the SIMRT technique or equal in both techniques. For α/ß oar ≥ 2-3 Gy, EQD2 and NTCP increase for the SIMRT treatment. CONCLUSIONS: A comparison between two radiotherapy techniques is presented. The SIBIMRT technique reduces EQD2 and NTCP for α/ß oar from 2 to 8 Gy.

Further insights in trichothiodistrophy: a clinical, microscopic, and ultrastructural study of 20 cases and literature review.

BACKGROUND: Trichothiodistrophy (TTD) is a rare autosomal recessive condition that is characterized by a specific congenital hair shaft dysplasia caused by deficiency of sulfur associated with a wide spectrum of multisystem abnormalities. In this article, we study clinical, microscopic, and ultrastructural findings of 20 patients with TTD with the aim to add further insights regarding to this rare condition. Additionally, analyses of our results are compared with those extracted from the literature in order to enhance its comprehensibility. MATERIALS AND METHODS: TWENTY CASES OF TTD WERE INCLUDED: 7 from Mexico and 14 from Spain. Clinical, microscopic, scanning electron microscopy (SEM) studies and X-ray microanalysis (XrMa) were carried out in all of them. Genetic studies were performed in all seven Mexican cases. Patients with xeroderma pigmentosum and xeroderma pigmentosum/TTD-complex were excluded. RESULTS: Cuticular changes and longitudinal crests of the hair shaft were demonstrated. These crests were irregular, disorganized, following the hair longest axis. Hair shaft sulfur deficiency was disposed discontinuously and intermittently rather than uniformly. This severe decrease of sulfur contents was located close to the trichoschisis areas. Only five patients did not show related disturbances. Micro-dolichocephaly was observed in five cases and represented the most frequent facial dysmorphism found. It is also remarkable that all patients with urologic malformations also combined diverse neurologic disorders. Moreover, three Mexican sisters demonstrated the coexistence of scarce pubic vellus hair, developmental delay, onychodystrophy, and maxillar/mandibullar hypoplasia. CONCLUSIONS: TTD phenotype has greatly varied from very subtle forms to severe alterations such as neurologic abnormalities, blindness, lamellar ichthyosis and gonadal malformations. Herein, a multisystem study should be performed mandatorily in patients diagnosed with TTD.

Neonatal erythroderma as a first manifestation of Menkes disease.

Menkes disease is an X-linked recessive lethal multisystemic disorder of copper metabolism. Progressive neurodegeneration, connective tissue disturbances, and peculiar kinky hair are the main manifestations. The low serum copper and ceruloplasmin suggests the diagnosis, which is confirmed by mutation analysis of the ATP7A gene. We report an exceptional presentation of classic Menkes disease with neonatal erythroderma. Genetic study revealed a deletion in exons 8 to 12 in the ATP7A gene. This study could allow pediatricians and pediatric dermatologists to diagnose the disorder as early as possible to establish prompt treatment with parenteral copper-histidine supplementation to improve prognosis.

Congenital atrichia and hypotrichosis.

BACKGROUND: Alopecia present from birth includes a broad differential diagnosis and often represents a diagnostic and therapeutic challenge for the involved physician. DATA SOURCES: An initial correct diagnosis and classification is essential because structural hair defects may be the expression of a genetic disorder affecting hair growth, part of a congenital syndrome with accompanying hair malformations, or a marker for an underlying metabolic disorder and may impact the mental and physical development of a child. Pathological hair loss rarely occurs in the first year of life; however, it may be a leading symptom of many congenital diseases. RESULTS: In recent years, the clinical and microscopic features of hereditary hair shaft disorders have been characterized and classified. Furthermore, significant progress has been made in our knowledge of genes that control the normal development and differentiation of hair follicles, and thus the research is to define and classify the hair disorders within a genetic basis. CONCLUSIONS: In this article we discuss several types of genotrichosis and provide a practical classification based on their clinical features.

Comparison of genetic versus clinical diagnosis in familial hypercholesterolemia.

Early diagnosis is important in familial hypercholesterolemia (FH), a highly atherogenic condition, but internationally agreed clinical diagnostic criteria are lacking. Genetic testing for low-density lipoprotein (LDL) receptor (LDLR) and apolipoprotein B (APOB) gene defects is the preferable diagnostic method, but the best phenotype indication to proceed with genetic diagnosis has not been established. The aim of this study was to assess the predictive and accuracy values of standard diagnostic criteria for detecting disease-causing mutations in 825 subjects with clinical FH aged > or =14 years from 3 lipid clinics in Spain. All subjects underwent thorough genetic testing for the detection of LDLR and APOB defects using the Lipochip platform. FH-causing mutations were detected in 459 subjects (55.6%). By logistic regression analysis, familial or personal history of tendon xanthoma (TX) and LDL cholesterol were strongly associated with genetic diagnosis (p <0.005, R(2) = 0.41). In subjects without familial or personal histories of TX, the diagnostic criteria for FH of the Make Early Diagnosis to Prevent Early Deaths (MEDPED) project, based on age-specific LDL cholesterol thresholds, showed sensitivity of 72.4%, specificity of 71.1%, and accuracy of 71.6%. LDL cholesterol > or =190 mg/dl in subjects with familial or personal histories of TX and > or =220, > or =225, and > or =235 mg/dl in those without such histories aged <30, 30 to 39, and > or =40 years, respectively, showed sensitivity of 91.1%, specificity of 71.1%, and accuracy of 74.2% for a positive genetic diagnosis. This new set of diagnostic criteria for FH was validated in an independent group of 440 subjects from 6 additional Spanish lipid clinics. In conclusion, TX and age-adjusted LDL cholesterol cut-off values have the highest value for clinical diagnosis and indication of genetic testing in FH.

Prostate planning treatment volume margin calculation based on the ExacTrac X-Ray 6D image-guided system: margins for various clinical implementations.

PURPOSE: To assess the prostate motion from day-to-day setup, as well as during irradiation time, to calculate planning target volume (PTV) margins. PTV margins differ depending on the clinical implementation of an image-guided system. Three cases were considered in this study: daily bony anatomy match, center of gravity of the implanted marker seeds calculated with a limited number of imaged days, and daily online correction based on implanted marker seeds. METHODS AND MATERIALS: A cohort of 30 nonrandomized patients and 1,330 pairs of stereoscopic kV images have been used to determine the prostate movement. The commercial image guided positioning tool employed was ExacTrac X-Ray 6D (BrainLAB AG, Feldkirchen, Germany). RESULTS: Planning target volume margins such that a minimum of 95% of the prescribed dose covers the clinical target volume for 90% of the population are presented. PTV margins based on daily bony anatomy match, including intrafraction correction, would be 11.5, 13.5, and 4.5 mm in the anterior-posterior, superior-inferior, and right-left directions, respectively. This margin can be further reduced to 8.1, 8.6, and 4.8 mm (including intrafraction motion) if implanted marker seeds are used. Finally, daily on line correction based on marker seeds would result in the smallest of the studied margins: 4.7, 6.2, and 1.9 mm. CONCLUSION: Planning target volume margins are dependent on the local clinical use of the image-guided RT system available in any radiotherapy department.

Diffuse and segmental variants of cutaneous leiomyomatosis: novel mutations in the fumarate hydratase gene and review of the literature.

Multiple cutaneous and uterine leiomyomatosis (MCUL; OMIM 150800) is an autosomal dominantly inherited disease characterized by leiomyomas of the skin and uterine leiomyomas. Recently, association of MCUL with different forms of renal cancer has been described. This syndrome is referred to as hereditary leiomyomatosis and renal cell cancer (OMIM 605839). Both disorders result from heterozygous germline mutations in the fumarate hydratase (FH) gene that may function as a tumor suppressor. Interestingly, cutaneous leiomyomas do not only manifest in a diffuse and symmetric fashion. Rather frequently, a segmental or band-like manifestation pattern can be observed, usually following the lines of Blaschko. Here, we sought to elucidate the molecular basis of diffuse and segmental cutaneous leiomyomatosis in six unrelated Dutch and Spanish patients and their families. We identified six novel FH mutations, including one missense and one nonsense mutation, two deletions and two splice-site mutations. The segmental phenotype that was observed in various patients with FH mutations most likely reflects a type 2 segmental manifestation of cutaneous leiomyomatosis as previously also described for other autosomal dominantly inherited skin diseases. The results presented here extend the current data on the molecular basis of familial cutaneous leiomyomatosis and comprise, to the best of our knowledge, the first genetic study in Dutch and Spanish patients with this disorder. In addition, we review the clinical and molecular aspects of the disease.

Dermoscopy in epidermodysplasia verruciformis.

BACKGROUND: Epidermodysplasia verruciformis (EV) is a rare autosomal recessive genodermatosis characterized by an impairment of cellular immunity. It clinically manifests as widespread, long-lasting, pityriasis versicolor-like macules and flat, wart-like papules, usually occurring in early childhood. There is a risk of development of multiple skin cancers in the third decade, primarily in sun-exposed skin. EV-associated human papillomaviruses have been implicated in a number of cutaneous lesions in non-EV populations, such as seborrheic keratoses or psoriasis. They have also been implicated in the development of nonmelanoma skin cancer, especially in immunosuppressed patients. Patients affected with EV are not able to eliminate oncogenic viruses within lesions, leading to a malignant transformation. OBJECTIVE: To describe the dermoscopic characteristics of EV cutaneous tumors by performing histopathologic correlation. METHODS AND MATERIALS: Cutaneous lesions and tumors from two patients affected by EV were included. Clinical and dermoscopic images were obtained and excision with ulterior histopathology was performed in all suspicious tumors and characteristic lesions. RESULTS: Dermoscopy and histology of pityiriasis versicolor-like macules, wart-like papules, seborrheic keratosis-like tumors, psoriasis-like plaques, collision tumors, and Bowen in situ carcinoma are described. CONCLUSIONS: Dermoscopy in EV tumors correlated with histopathologic findings and improved the differential diagnosis of tumors in this disease.