Low dose of isotretinoin: A comprehensive review.

Isotretinoin is a first-generation retinoid initially approved for the treatment of severe cases of acne vulgaris (nodulocystic acne). Because of its broad anti-inflammatory and immunomodulatory properties, it has been used beyond its initial approval in a myriad of other indications. Adverse effects of isotretinoin vary from xerosis to teratogenicity. Herein, we reviewed the literature, through date-unlimited PubMed search, from inception till December 2019, using the following search terms: "low-dose isotretinoin" and "dermatology," "isotretinoin and safety," "isotretinoin, off-label uses," "isotretinoin and male fertility," "isotretinoin, iPLEDGE system," aiming to deliver a therapeutic update relevant to clinical practice. All English-language articles were considered with no limitation based on the articles' type. Low-dose isotretinoin is not limited to old and novel dermatological conditions, but also showed promising results in the field of infertility and safety in the field of gastroenterology. We also highlight on the safety profile of the drug and experts' recommendations to enhance safety measures to decrease fetal risk while on isotretinoin.

Spitz nevus arising upon a congenital glomuvenous malformation.

There are several reports of the collision of vascular and pigmentary anomalies (e.g., phakomatosis pigmentovascularis) and the association between congenital melanocytic nevi and infantile hemangiomas. We report a case of Spitz nevus arising in skin overlying a congenital plaque-like glomuvenous malformation (GVM). This is the first report of a Spitz nevus arising in direct contiguity to a GVM.

The efficacy of vorinostat in combination with interferon alpha and extracorporeal photopheresis in late stage mycosis fungoides and Sezary syndrome.

OBJECTIVE: Long-term survival for advanced stages of mycosis fungoides (MF) may be beneficially affected by the use of multimodality therapy. We aim to evaluate the activity of vorinostat in combination with interferon (IFN) alpha and extracorporeal photopheresis (ECP) with persistent, progressive advanced stage MF and Sezary syndrome (SS). PATIENTS AND METHODS: Three patients with stage IIB-IVA MF/SS were treated with vorinostat 400 mg/day/po. Vorinostat was added to ongoing ECP and IFN-alpha-2a therapies in all three patients. RESULTS: The patient with stage IIB MF achieved a complete response. The patient with SS showed a stable disease of less than 50 percent improvement in body surface area with reduction in the sizes of axillary and inguinal lymph nodes. A partial remission was maintained for 24 weeks in the patient with stage IVA MF, followed by rapid disease progression under treatment which led to cessation of vorinostat treatment due to study criteria as well as serious side effects. CONCLUSION: Our experience in this case series is suggestive of the synergistic effect of vorinostat in combination with IFN and ECP and supports the efficacy of vorinostat in inducing prolonged responses in patients with progressive disease and/or stable disease in otherwise progressive and treatment refractory late stage MF/SS.

Remission of severe autoimmune bullous disorders induced by long-term extracorporeal photochemotherapy.

Pemphigus vulgaris (PV) and epidermolysis bullosa acquisita (EBA) sometimes resist treatments. In drug-resistant cases, adjuvant treatment with extracorporeal photochemotherapy (ECP) has been reported to induce remission. However, limited numbers of patients have been reported up to date. Eleven patients with drug-resistant autoimmune bullous diseases have been treated with ECP (8 patients with PV, 3 patients with EBA). The introduction of ECP to systemic therapies of the patients with PV resulted in complete response (CR) after a limited cycle (2-6 cycles) in all, except one patient. Prednisolone doses could be tapered in all patients. ECP resulted in CR in two patients while improvement was partial in one patient with EBA after 3-6 cycles. Our patients demonstrate the efficacy of long-term ECP to be tried in the treatment of aggressive autoimmune bullous disorders. The treatment has produced a remarkable corticosteroid-sparing effect while inducing clinical remission.

Sweet's syndrome in familial Mediterranean fever: possible continuum of the neutrophilic reaction as a new cutaneous feature of FMF.

Sweet's syndrome (SS) or acute febrile neutrophilic dermatosis is an uncommon disorder that often occurs in association with other systemic diseases. In its systemic manifestation, SS resembles familial Mediterranean fever (FMF) in many aspects. Although the exact pathogenesis of SS and FMF is not yet clear, their clinical similarities and simultaneous occurrence suggest a possible common underlying mechanism and may represent a continuum of a reactive neutrophilic condition.

Dermatoscopic findings of cutaneous mastocytosis.

BACKGROUND: Mastocytosis is a disorder characterized by the accumulation of mast cells in various organs, most commonly in the skin. Cutaneous mastocytosis (CM) can be classified as nodular CM with solitary or multiple lesions, diffuse CM (erythroderma), and maculopapular CM including the papular/plaque variant, urticaria pigmentosa (UP) and telangiectasia macularis eruptiva perstans (TMEP). OBJECTIVE: To evaluate the dermatoscopic features of cutaneous mastocytosis. METHODS: We reviewed the dermatoscopic images of 6 patients who had different variants of cutaneous mastocytosis and who attended the Departments of Dermatology at the Medical University of Ankara, Turkey, and the Medical University of Vienna, Austria. RESULTS: In UP and in the papular variant of CM the most common structures seen by dermatoscopy were brown reticular lines (pigment network). In TMEP we observed telangiectatic vessels arranged in a reticular pattern. CONCLUSION: Skin lesions of mastocytosis may exhibit a pigment network, a dermatoscopic feature said to be characteristic of melanocytic lesions. We were also able to identify a new dermatoscopic feature, a reticular vascular pattern that is characteristic of a clinical variant of mastocytosis known as TMEP. This feature may help to differentiate TMEP from other variants of mastocytosis and from other exanthematous skin diseases.

Comedonal, cornifying and hypertrophic Darier's disease in the same patient: a Darier combination.

Our 42-year-old patient had comedonal Darier's disease (DD) on the face, comedonal cornifying DD on the upper back, and hypertrophic DD on both legs. Biopsies taken from face, upper back and medial sides of the legs were found to be compatible with these clinical subtypes. The comedonal type was in the classical place, but the hypertrophic and cornifying types were not in the usual sites. In addition to the classic histopathology of DD, we noted multiple, warty dyskeratoma-like structures in the comedonal type, marked compact hyperkeratosis in the cornifying type, and marked papillomatosis in the hypertrophic type.

Post-renal transplantation Leser-Trélat sign associated with carcinoma of the gallbladder: a rare association.

The sign of Leser-Trélat represents the sudden appearance of multiple seborrheic keratoses in association with an underlying malignancy. The most common associated neoplasms belong to the gastrointestinal tract, mainly the stomach and colon. In the literature, there is only one case of gallbladder carcinoma associated with the Leser-Trélat sign. Thus, the hallmark of our patient is post-renal transplant malignancy-associated Leser-Trélat, which has not been reported before. Here, we report on a 57-year-old man who presented with a sudden increase in the number and size of seborrheic keratoses, particularly on sun-exposed areas 24 years after renal transplantation. The search for an underlying malignancy showed the presence of an adenocarcinoma of the gallbladder which had metastasized to the liver.

Juvenile non-hyaline fibromatosis: juvenile hyaline fibromatosis without prominent hyaline changes.

Juvenile hyaline fibromatosis (JHF) is a rare autosomal recessive disease of the connective tissue. It is characterized by papulonodular skin lesions, soft tissue masses, gingival hypertrophy, osteolytic bone lesions and flexion contractures of the large joints. Here, we report a 14-year-old girl with characteristic clinical features of JHF with early fatal outcome. Dermatopathologic examination of the early lesions however constantly lacked the so-called hyalin changes in multiple skin biopsies. According to our experience; dermatopathological features of this entity is not often and always consists of classical hyalinisation. Only larger lesions with long duration should expected to be exhibiting those features. Therefore we suggest that; JHF may often present itself as Juvenile Non-Hyaline Fibromatosis: JHF without prominent hyaline changes. And thus this fact should not change the actual diagnosis and prognostic implications.

Mycosis fungoides and Sezary syndrome: therapeutic approach and outcome in 113 patients.

BACKGROUND: Mycosis fungoides (MF) and Sezary syndrome (SS) are the most common forms of cutaneous T-cell lymphoma (CTCL). Various topical and systemic therapeutic alternatives are available, but there is no standard or definite curative treatment regimen. When making a decision about the appropriate treatment modality, the age and compliance of the patient, stage of the disease, treatment accessibility, and previous treatment history should be considered. AIM: To determine the therapeutic response of patients with MF and SS to different treatment modalities. Patients were evaluated with respect to their clinical and demographic features. METHODS: One hundred and thirteen patients diagnosed clinically and dermatopathologically with MF and SS between March 1984 and June 2001 were included in the study. RESULTS: Of the 113 patients studied, 110 had a diagnosis of MF and three had a diagnosis of SS; 101 patients (89.4%) were diagnosed with early stage (IA, IB, IIA) and 12 (10.6%) with late stage (IIB, III, IVA, IVB) disease. The age at diagnosis varied between 12 and 81 years (mean, 45.6+/-15.8 years). Fifty-five (48.7%) patients were male and 58 (51.3%) were female. The duration of the skin lesions varied between 1.5 months and 32 years (mean, 6.1 years). Psoralen plus UVA (PUVA) was the most commonly used initial treatment modality in early stage disease (91%), with a complete remission (CR) rate of 80.4%. With PUVA+interferon-alpha (INF-alpha) treatment, CR was 57% in the early stages and 33.3% in the late stages. For late stage disease, systemic therapies, such as pentostatin, gemcitabine, and fludarabine, alone or in combination with INF-alpha, were preferred. Of the 113 patients, eight (7% of the total and 57.1% of the advanced stage cases) died of MF; 21.4% of the late stage patients showed partial remission and 14.2% showed CR. None of the patients diagnosed with early stage disease died of MF, but two (1.9%) progressed to late stage disease. CONCLUSIONS: PUVA and PUVA+INF-alpha are effective treatment modalities, especially for early stage MF. Once the disease has progressed, both MF and SS are very resistant to treatment regimens, including chemotherapeutic agents. It is important to diagnose and treat these diseases, especially MF, in the early stages for lasting remission.

HLA-class 1 and class 2 antigens in Turkish patients with pemphigus.

BACKGROUND: Pemphigus is an autoimmune disease which is more frequently seen in certain ethnic groups such as Jews. It is thought that exogenous factors may induce pemphigus in genetically predisposed individuals. Recent reports on HLA antigens indicate an increased frequency of HLA-class II antigens particularly HLA-DR4 among Jewish patients. Herein we investigated the antigen frequencies of HLA-A, B, C, HLA-DR and DQ in Turkish patients with pemphigus. METHODS: HLA class I and II antigens were typed by microdroplet lymphocyte cytotoxicity test in 33 patients with pemphigus and 100 healthy individuals. RESULTS: HLA-B35, B44, CW4, DR4, DR14, DQ8 and DQ4 antigens were significantly high in the study group whereas HLA-DR11, DQ7 and DQ2 antigens were high among the controls. The most striking differences were observed in HLA class II antigens. HLA DR14-DQ8 and HLA B35-DR14 haplotypes were the most frequently observed ones in the study group. CONCLUSIONS: We postulate that HLA-B35, B44, CW4, DR4, DR14, DQ4 and DQ8 antigens may be responsible for susceptibility to pemphigus while HLA-DR11, DQ7 and DQ2 antigens may have a protective role in the Turkish population.

Multifocal papillomavirus epithelial hyperplasia: successful treatment with CO2 laser therapy combined with interferon alpha-2b.

Human papilloma virus (HPV) infections of the oral mucosa presents with various clinical and histopathologic features in relation with the causative HPV type and chronicity and the extent of the infection.1 The entity is known by several names based on histopathologic variations such as focal epithelial hyperplasia, oral florid papillomatosis, verrucous hyperplasia, oral florid verrucosis, and Ackerman's tumor. In recent years, the term multifocal papillomavirus epithelial hyperplasia (MPVEH) has been proposed to define the variant that usually occurs in childhood and is characterized by diffuse confluent papillomatous lesions in the oral mucosa.1 Despite the lesions' benign appearance, early diagnosis and therapy of MPVEH is essential because of its high capacity for progression and its tendency for malign degeneration.

Juvenile colloid milium associated with conjunctival and gingival involvement.

Juvenile colloid milium is an uncommon cutaneous disease characterized by translucent papules distributed on sun-exposed areas with early onset. Association of juvenile colloid milium with conjunctival and gingival deposits is uncommon and interesting. We report a case of juvenile colloid milium associated with conjunctival and gingivai deposits of an amyloid-like homogeneous eosinophilic material. It seems that all 3 of these in our patient may be different expressions of the same pathologic disease.

Cutaneous silica granuloma in a child.

A 12-year-old girl had a 4-year history of two asymptomatic, sharply demarcated, granulomatous lesions on her face. The lesions did not respond to topical steroids and histopathologic examination of biopsy specimens showed granulomatous inflammation. Since cutaneous leishmaniasis is endemic where the patient lived, she was diagnosed as chronic cutaneous leishmaniasis but did not respond to meglumine antimoniate treatment. Reexamination of the biopsy specimens under polarized light revealed numerous birefringent crystalline particles, and cutaneous silica granuloma was the final diagnosis. The lesions were treated with intralesional triamcinolone acetonide and completely disappeared. We report this case of cutaneous silica granuloma, which is unusual in children, and emphasize the importance of polarized light microscopic examination of granulomatous skin diseases.