Juan Ferrando

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

Abstract:  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.

Premature familial sebaceous hyperplasia: Successful response to oral isotretinoin in three patients

Each of the eight transmitted KOH images (four positive and four negative) were correctly interpreted as containing hyphae, or not, by at least 95.8% of the initial panel of 24 dermatologists. After retransmission of these eight images via the Picasso System, requiring an additional compression and decompression, seven of the eight images were correctly interpreted as containing hyphae, or not, by at least 94.4% of the second panel of 18 dermatologists, and 83.3% of this second panel interpreted the eighth correctly. There were no significant differences in diagnostic accuracies of any of the eight KOH images between the two evaluating panels of dermatologists, suggesting that transmission of the images did not reduce their correct interpretation.

Papuloerythroderma of Ofuji: A Report of 2 Cases Including the First European Case Associated with Visceral Carcinoma

Papuloerythroderma (PE) is a rare type of erythroderma of the elderly which results from the coalescence of sheets of papules that spare skin folds, with peripheral eosinophilia in most cases. Skin biopsy shows a nonspecific eczematous pattern with a mature T cell lymphocytic and eosinophilic infiltrate with Langerhans cells in the dermis. We report 2 cases of PE. The 1st case, in which no underlying malignancy could be found, responded partially to oral etretinate, topical steroid creams and tar derivates. The 2nd case did not respond to high-dose oral steroids and was associated with adenocarcinoma of the colon, with a fatal outcome. PE has been associated with lymphoma and carcinoma. We report the first European case of PE associated with visceral carcinoma and review the cases reported in the western literature.

Lichenoid Tri-Keratosis (Kaposi-Bureau-Barrière-Grupper)

A case of peculiar eruption in a 43-year-old man is reported. The eruption was papular, polymorphic, hyperkeratotic, and lichenoid appearing on 4dry skin with patches, linear striation and Sverrucous

Paraneoplastic Pemphigus: A Case of Long-Term Survival Associated with Systemic Lupus erythematosus and Polymyositis

A 35-year-old man presented with a generalized bullous eruption and oral ulceration. He had been diagnosed as having systemic lupus erythematosus and pelvic Castleman disease (hyaline-vascular type) in the past. Histologic, direct and indirect immunofluorescence and immunoprecipitation studies confirmed a diagnosis of paraneoplastic pemphigus (PNP). Initially several medical treatments were tried unsuccessfully. The pelvic tumor was surgically removed and the mucocutaneous lesions slowly regressed. Four years after presentation, he developed polymyositis which was completely controlled with short courses of corticosteroids. There was no evidence of relapse of PNP or lupus erythematosus at that time. At the 6-year follow-up he showed no clinical evidence of PNP, lupus erythematosus or polymyositis without requiring immunosuppressive therapy. This case emphasizes the fact that patients with benign-neoplasm-associated PNP may undergo complete remission of the autoimmune disease upon complete excision of the tumor. This case also stresses the possible association of PNP with other autoimmune diseases such as lupus erythematosus and polymyositis.

Congenital atrichia and hypotrichosis

BackgroundAlopecia present from birth includes a broad differential diagnosis and often represents a diagnostic and therapeutic challenge for the involved physician.Data sourcesAn 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.ResultsIn 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.ConclusionsIn this article we discuss several types of genotrichosis and provide a practical classification based on their clinical features.

Monilethrix: A New Family with the Novel Mutation in KRT81 Gene.

two public health antiretroviral clinics that documented the prevalence of virologic failure and genotypic antiretroviral resistance. A threshold hair concentration indicating longer term LPV exposure was instrumental in determining the etiology of virologic failure and identifying patients in need of adherence counseling or resistance testing.[4] In another study on 43 HIV-infected patients, significant association was found between HIV ribonucleic acid below 50 copies/ml and indinavir concentrations in hair but not in plasma.[5]

Solitary congenital nodular calcification of winer located on the ear: report of two cases

Abstract: Solitary congenital nodular calcification of the skin is a form of cutaneous caicinosis. it appears as a small, firm nodule on the head and extremities of young infants. The histogenesis of this condition is controversial. We cared for two patients with the nodule on the ear.

Annular Plaques in the Skin Folds: 4 Cases of lichen Planus Pigmentosus-inversus

We report 4 patients with relatively asymptomatic, annular brownish plaques arising in the skin creases.The lesions had remained stable for months despite many topical treatments. Histological examination revealed an atrophic epidermis with a dermal lichenoid inflammatory infiltrate showing marked pigmentary incontinence.These clinical and pathological features were consistent with lichen planus pigmentosus-inversus,a rare, recently described variant of lichen planus, with only 10 cases reported to date. It has been suggested that he intensity and speed of onset of the inflammatory response could be modulated by keratinocyte surface markers, which could also determine the typical morphology of the lesions of this disease.

Renal amyloidosis secondary to acne conglobata.

A 62-year-old white man had, since the age of 20, acne conglobata affecting predominantly the back, buttocks, and abdomen (Fig. 1). One year before hospitalization, proteinuria was detected. Five months later, proteinuria was persistent and renal failure had appeared. Two months before admission, surgical excision of chronic suppurative skin lesions of the buttocks was performed. One month before admission, serum creatinine was 5.9 mg/dl and the hematocrit 25.6%. The patient was hospitalized because of diarrhea, vomiting, drowsiness and progressive dispnea of 3 weeks duration, with oliguria in the last 48 hours. On examination, the patient appeared to be chronically ill, with axilar temperature of 36.5C, the blood pressure was 120/60 mmHg, the pulse rate, 100/min. He was stuporous and asterixis was evident. Cutaneous lesions of acne conglobata were present on the back, buttocks, and abdomen. Laboratory studies showed a hematocrit of 21.2% and a leukocyte count of 16,200/fi\ with 85% neutrophils, 4% lymphocytes, and 11 % monocytes. The blood urea nitrogen level was 115 mg/dl, and the creatinine level was 12.5 mg/dl. The calcium level was 6.3 mg/dl; the phosphorus level, 8.5 mg/dl; and uric acid, 2.7 mg/dl. The total serum protein level was 6.1 g/l (albumin 2.13 g/l, globulins 3.97 g/l). No serum M-component was present. Serum glucose, sodium, potassium, and bilirubin were within normal limits. Urine sediment contained 20 leukocytes per high-powered field. The 24-hour proteinuria ranged between 7 and 15 g. There was no evidence of Bence-Jones protein. Coombs test, rheumatoid factor, antinuclear antibodies, serum complement and serologics tests for syphilis were negative or normal. X-rays of the chest and abdomen were normal. A skin biopsy showed inflammatory infiltrate around the follicles with hyperkeratinization of the neck of the follicles with formation of abscesses in the dermis. Amiloid stains (Congo red, crystal violet and thioflavine) were negative. Renal ultrasound showed normal-sized kidneys. A renal biopsy was performed (Fig. 2). Light microscopy revealed