Markus Braun-Falco

Loss-of-Function Mutations in the Keratin 5 Gene Lead to Dowling-Degos Disease

Dowling-Degos disease (DDD) is an autosomal dominant genodermatosis characterized by progressive and disfiguring reticulate hyperpigmentation of the flexures. We performed a genomewide linkage analysis of two German families and mapped DDD to chromosome 12q, with a total LOD score of 4.42 ( theta =0.0) for marker D12S368. This region includes the keratin gene cluster, which we screened for mutations. We identified loss-of-function mutations in the keratin 5 gene (KRT5) in all affected family members and in six unrelated patients with DDD. These represent the first identified mutations that lead to haploinsufficiency in a keratin gene. The identification of loss-of-function mutations, along with the results from additional functional studies, suggest a crucial role for keratins in the organization of cell adhesion, melanosome uptake, organelle transport, and nuclear anchorage.

Successful treatment of nail lichen planus with alitretinoin: report of 2 cases and review of the literature.

Background: Treatment of nail lichen planus (LP) is difficult and an optimal therapy is lacking. Objective: To report additional cases to the scant existing literature to learn more about therapeutic options for nail LP. Methods: A regimen of 30 mg alitretinoin daily in 2 cases of nail LP over a period of 9 and 8 months, respectively. Results: In either case, nail changes showed marked improvement under oral alitretinoin therapy within 2 and 4 months, respectively. In both patients, affected nails with end-stage destructive pterygium were resistant to any previously applied therapy. Conclusion: Alitretinoin is an effective treatment option for nail LP. We recommend early diagnosis of nail LP and early initiation of systemic therapy with alitretinoin to prevent the development of pterygium and permanent nail damage. However, further clinical studies are needed to establish reliable guidelines for nail LP therapy.

Association of Urticaria pigmentosa with Café-au-Lait Spots, Neurofibromas and Neurofibroma-Like Neoplasms: A Mere Coincidence?

Background: Urticaria pigmentosa (UP) is characterized by dense aggregates of mast cells in the dermis. There is consistent evidence from the literature that mast cells may play a pathogenetic role in the development of neurofibromas and other tumors. Objective: To study the concomitant appearance of UP with neurofibromas and neurofibroma-like neoplasms. Methods: We analyzed 31,752 records of patients examined at the Department of Dermatology in the year 2000, looking for UP and associated neurofibromas and neurofibroma-like neoplasms in persons younger than 18 years. Results: We identified a total of 27 patients suffering from UP, with 16 persons younger than 18 years. One 12-year-old Caucasian boy demonstrated multiple cutaneous mastocytomas consistent with the diagnosis of UP. On his trunk, four café-au-lait spots were found. A cutaneous neurofibroma was confirmed by skin biopsy. Magnetic resonance imaging detected multiple neoplasms located at the nerve roots of the spine, resembling plexiform neurofibromas. Conclusions: There may be a concomitant appearance of UP and neoplasms, with mast cells possibly playing a causative role. The existence of neoplasms, including neurofibromas and neurofibroma-like lesions should be considered when examining UP cases.

Recurring Localized Scarlatiniform Scaled Erythema Féréol-Besnier

Recurring scarlatiniform scaled erythema of Féréol-Besnier is a rare disease characterized by recurrent episodes of a prodromal phase with general malaise, head and muscle aches, gastrointestinal complaints and fever followed by an erythematous rash leading to extensive desquamation of the involved skin. It exists in a generalized and localized variant, the latter mainly involving the hands and feet. Its cause is unknown, although it has been speculated that a hyperergic reaction to infectious agents or medications may be etiopathologically involved. A typical case of the localized variant of this obscure disease is described and the common literature is reviewed.

Epidermotropic scrotal metastasis of colorectal cancer.

Dear Editor: Colorectal cancer is one of the most frequent malignancies in men and women, with an incidence around 50/100,000, counting for approximately 10% of all newly diagnosed cancer cases and for 10% of all cancer deaths. After total resection of the primary tumor, relapses occur mainly within the first 2–3 years of follow-up, with extramural local recurrences (e.g., peritoneum, pelvis) and metastases to the liver, lungs, and bone as the most common sites of tumor spread. Herein, we report the very unusual occurrence of epidermotropic cutaneous metastases of colorectal cancer at the scrotum as the first site of disseminated tumor spread. A 69-year-old man presented with an asymptomatic, rapidly developing erythematous soft plaque at the right scrotum measuring up to 2 cm in diameter. Five months previously, a colorectal adenocarcinoma (pT4, N0, G3, L1) had been surgically resected and combined radiochemotherapy with 5-fluorouracil and radiation of the pelvis was just completed. Therefore, the red plaque was first interpreted as an acute radiodermatitis. Within two weeks, a second lesion developed in the groin, which appeared as a dome-shaped nodule rather untypical for dermatitis. Histopathologic evaluation of the two tumors demonstrated islets of adenocarcinoma within the epidermis and dermis. The morphology of the tumor cells was similar to that of the tumor in the rectum. Staging at this time revealed no evidence of visceral metastases. Thereafter, the patient developed generalized lymphogenic spread of colorectal carcinoma and died 6 months later of a cerebral insult. Cutaneous metastases in colorectal cancer occur in approximately 4.4% of cases according to a survey on 413 patients with metastatic disease. The probability of these metastases being the first sign of extranodal spread is even lower with 3%. Skin involvement of colorectal carcinoma occurs predominantly at the abdominal wall or pelvis and seems to favor sites of previous incisions. The scrotum as the first site of cutaneous spread is very uncommon. Histopathologically, cutaneous metastases are usually confined to the dermis or subcutaneous fat without involvement of the epidermis. Epidermotropism as it occurred in the present case is exceedingly rare. The fact that the metastases evolved during and within the area of radiation indicates a highly aggressive biological behavior. Cutaneous metastases are usually known to signify widespread, terminal disease, with a discouraging life expectancy after diagnosis estimated as being between 4.4 and 18 months. Although a few The authors indicated no potential conflicts of interest.

Lichen planus with associated myasthenia gravis-successful treatment with acitretin

ejd.2013.2162 Auteur(s) : Adel Alsenaid dr.senaid@gmail.com, Angelika Lang, Thomas Ruzicka, Markus Braun-Falco, Ronald Wolf Department of Dermatology and Allergology Ludwig-Maximilian University Munich Frauenlobstrasse. 9-11 80337 Munich Germany Lichen planus (LP) is a common chronic inflammatory disease of unknown origin, usually affecting middle-aged women. LP can involve the skin, mucous membranes, nails and hair. LP is characterized by pruritic violaceous papules and plaques, especially on the [...]

Granular parakeratosis – a clinical-pathological correlation of 10 cases

Background: Granular parakeratosis describes chronic skin lesions within the intertriginous areas that demonstrate microscopically parakeratosis together with retention of keratohyalin granules within a thickened stratum corneum. Granular parakeratosis is rarely diagnosed, since it is still relatively unknown within the differential diagnoses of intertriginous eruptions, and a skin biopsy is required for diagnosis. In order to gain insight into the clinical‐histopathologic correlation, we present 10 cases of granular parakeratosis.

Localized sclerosis of the scalp (alopecia porphyrinica) as predominant presentation of porphyria cutanea tarda

© 2007 The Authors 1125 JEADV 2007, 21, 1105–1147 Journal compilation

Eight Novel Mutations Confirm the Role of AAGAB in Punctate Palmoplantar Keratoderma Type 1 (Buschke-Fischer-Brauer) and Show Broad Phenotypic Variability

Punctate palmoplantar keratoderma (PPKP1; Buschke-Fischer-Brauer) is a rare autosomal dominant inherited skin disease characterized by multiple hyperkeratotic papules involving the palms and soles. Mutations have been found at 2 loci, on chromosomes 15q22-15q24 and 8q24.13-8q24.21. We recently identified mutations in 3 families, in the AAGAB gene on 15q, which encodes the alpha- and gamma-adaptin-binding protein p34. The current study examined 14 additional families, comprising a total of 26 affected individuals and identified 8 novel mutations in 9 families. In one family a mutation that was present only in the affected individuals was found, and in 4 other families, previously reported mutations were found (1, 2). These results confirm the role of AAGAB in PPKP1. Our findings suggest that there is no correlation with age, but with mechanical factors. No additional obvious genotype-phenotype correlation was observed, even when comparing different types of mutations. Rather, identical genotypes presented a very broad interfamilial and intrafamilial variability of phenotypes.

Pyoderma gangrenosum, acne, suppurative hidradenitis (PASH) and polycystic ovary syndrome: Coincidentally or aetiologically connected?

The clinical triad of pyoderma gangrenosum, acne conglobata and hidradenitis suppurativa has been named PASH syndrome. Polycystic ovary syndrome (PCOS) is associated with hyperandrogenism and inflammation. Hidradenitis suppurativa, like acne vulgaris, may be a feature of hyperandrogenism. Obesity may be associated with both hidradenitis suppurativa and PCOS. We describe a possible association between PASH syndrome and PCOS.