ß2-Microglobulin deficiency causes a complex immunodeficiency of the innate and adaptive immune system.

BACKGROUND: Most patients with MHC class I (MHC-I) deficiency carry genetic defects in transporter associated with antigen processing 1 (TAP1) or TAP2. The clinical presentation can vary, and about half of the patients have severe skin disease. Previously, one report described ß2-microglobulin (ß2m) deficiency as another monogenetic cause of MHC-I deficiency, but no further immunologic evaluation was performed. OBJECTIVE: We sought to describe the molecular and immunologic features of ß2m deficiency in 2 Turkish siblings with new diagnoses. METHODS: Based on clinical and serologic findings, the genetic defect was detected by means of candidate gene analysis. The immunologic characterization comprises flow cytometry, ELISA, functional assays, and immunohistochemistry. RESULTS: Here we provide the first extensive clinical and immunologic description of ß2m deficiency in 2 siblings. The sister had recurrent respiratory tract infections and severe skin disease, whereas the brother was fairly asymptomatic but had bronchiectasis. Not only polymorphic MHC-I but also the related CD1a, CD1b, CD1c, and neonatal Fc receptor molecules were absent from the surfaces of ß2m-deficient cells. Absent neonatal Fc receptor surface expression led to low serum IgG and albumin levels in both siblings, whereas the heterozygous parents had normal results for all tested parameters except ß2m mRNA (B2M) expression. Similar to TAP deficiency in the absence of a regular CD8 T-cell compartment, CD8(+) γδ T cells were strongly expanded. Natural killer cells were normal in number but not "licensed to kill." CONCLUSION: The clinical presentation of patients with ß2m deficiency resembles that of patients with other forms of MHC-I deficiency, but because of the missing stabilizing effect of ß2m on other members of the MHC-I family, the immunologic defect is more extensive than in patients with TAP deficiency.

Treatment of ingrown toenail with proximolateral matrix partial excision and matrix phenolization.

PURPOSE: Ingrown toenail is one of the most common nail conditions. Although many surgical treatments are described for complicated cases, recurrence of pain and postoperative disability are common. We evaluated the long-term efficacy of proximolateral matrix partial excision followed by chemical matricectomy with phenol. METHODS: We performed 348 proximolateral partial matricectomies and phenol ablations in 225 patients with stage 2 or 3 ingrown toenail. Patients were examined weekly until full wound healing was achieved and were observed for 24 months to assess the long-term efficacy of the treatment. RESULTS: Short-term results were good. We observed only 1 recurrence during the 24-month follow-up period, at 8 months. The success rate was therefore 99.7%. No severe complications occurred. Cosmetic results were remarkably good. CONCLUSIONS: Proximolateral partial matricectomy with phenol ablation is an excellent surgical method for the treatment of ingrown toenails, having low morbidity and a high success rate, even in the long term.

Subungual glomus tumor: surgical and histopathologic evaluation.

Glomus tumor is a rare and benign vascular tumor, arising from neuromyoarterial glomus bodies. It is generally localized on the hand and especially the nail bed and is usually solitary. Pain, tenderness, and temperature sensitivity are the classic triad of symptoms of a glomus tumor. Owing to the small lesions and absence of specific skin features in the nail bed and nail matrix localizations, glomus tumor may not be taken into consideration. In particular, presentation of patients to practitioners of different disciplines for treatment of pain may cause diagnostic delays. Surgical excision is the most effective treatment approach and provides histopathologic diagnosis and rapid improvement of symptoms. This article describes a patient with a subungual glomus tumor for which surgical excision was performed.

Pachyonychia congenita type 2, N92S mutation of keratin 17 gene: clinical features, mutation analysis and pathological view.

Pachyonychia congenita (PC) type 2 is a rare inherited genetic disease characterized by hypertrophic nail dystrophy, palmoplantar hyperkeratosis and multiple pilosebaceous cysts. In some cases, natal teeth and hair abnormalities may be present. It is caused by mutations in keratin 17 or its expression partner keratin 6b. Here, an N92S (p.Asn92Ser) germline keratin 17 gene mutation in a pachyonychia congenita type 2 female patient is presented. The pedigree includes the 15 members of a family who showed a severe expression of the phenotype for six generations with a similar clinical picture consisting of sebaceous cysts, nail dystrophy, hyperkeratosis, hair abnormalities, natal teeth, hoarseness and hyperhydrosis. In conclusion, we emphasize the importance of diagnosing and managing pachyonychia congenita in childhood for the assistance of affected children and for the development of potential therapies.

Dermatofibroma on the palmar surface of the hand.

Case 1: A 58-year-old man presented with a solitary asymptomatic nodule on his thumb (Figure A). After trauma with a rusty nail approximately 20 years ago, he had developed a small papule, which had enlarged gradually for a few days initially before stabilizing. His personal and family medical histories were unremarkable. Dermatologic examination revealed a 1-cm crater-like nodule on the left palmar area. This was a firm and nontender lesion that was fixed to the overlying skin but moved freely from underlying structures. There were no similar lesions elsewhere on his body. Case 2: A 52-year-old man presented with a nodular lesion on the left palmar surface of his thumb. The 0.8-cm lesion was lightly colored, with a central cup-shaped epidermal depression and thin epidermis. The patient described an insect bite to the area 15 years earlier as the precipitating event. The firm and nontender lesion was fixed to the overlying skin but moved freely from underlying structures (Figure B). Case 3: A 36-year-old man consulted for a nodular lesion, located on his left palmar surface, that had not enlarged or changed since appearing 3 years ago. He described mechanical trauma to the area as precipitating the lesion. Clinical examination revealed a 0.6-cm, well-circumscribed nodule, with a dome shape and colored skin. Clinically, the nodular lesion appeared to be a benign tumor (Figure C). In each case, the nodule was excised totally and histopathologic examination revealed a well-circumscribed, nonencapsulated nodule within the mid-dermis. Thick, acellular collagen bundles were arranged randomly in short fascicles through the center of the lesion. Cellular areas consisting of histiocytes and fibroblasts with a storiform pattern at the periphery of lesion were observed, but nuclear atypia and mitotic activity were not. Results of immunohistochemical stain with CD34 were negative, but in all cases were strongly positive for Factor XIIIa. Slight epidermal hyperplasia was present with orthokeratotic hyperkeratosis and flattened rete ridges in the overlying epidermis (Figure A-1, Figure B-1, Figure C-1). The subcutaneous fat and adjacent skin were normal. No folliculosebaceous units at the periphery of the lesion were seen, but a few eccrine sweet glands were noted. No recurrence appeared in 18 months of follow-up.

Amiodarone-induced multiorgan toxicity with ocular findings on confocal microscopy.

Amiodarone is an antiarrhythmic medication that can adversely effect various organs including lungs, thyroid gland, liver, eyes, skin, and nerves. The risk of adverse effects increases with high doses and prolonged use. We report a 54-year-old female who presented with multiorgan toxicity after 8 months of low dose (200 mg/day) amiodarone treatment. The findings of confocal microscopy due to amiodarone-induced keratopathy are described. Amiodarone may cause multiorgan toxicity even at lower doses and for shorter treatment periods.

Genotype and Anterior Segment Phenotype in a Cohort of Turkish Patients with Lamellar Ichthyosis.

PURPOSE: To evaluate the ocular surface and topography findings of lamellar ichthyosis, and to investigate the correlation of these findings with mutations in TGM1, CYP4F22 and NIPAL4 genes. METHODS: Twelve patients with lamellar ichthyosis were evaluated. Routine ophthalmic examination including Schirmer 1, tear break-up time and ocular surface staining score, topography, and genetic evaluation for coding exons of TGM1, NIPAL4 and CYP4F22 genes were performed. RESULTS: The mean age of the patients was 19.75 ± 9.15 (range, 4-31) years. Mean Schirmer 1 scores of the right and the left eyes were similar (18.75 ± 3.10 mm). Mean tear break-up time of the right and the left eyes were 6.58 ± 2.74, 6.58 ± 3.02 seconds, respectively. Mean ocular surface staining grade was 0.36 ± 0.20 in the right, and 0.39 ± 0.17 in the left eyes. Keratoconus was detected in two patients. Two patients with bilateral cataract formation were found. Genetic sequencing revealed that one case had homozygous R326X mutation in the CYP4F22 gene, two cases had homozygous A176D mutation in the NIPAL4 gene, and three had homozygous M1T mutation in the same gene. Mutations were detected in patients with keratoconus and in a patient with bilateral cataract formation. CONCLUSIONS: In lamellar ichthyosis, eyelid malformations together with decreased tear break-up time might cause sight-threatening complications. Genetic counseling for mutations might enable the physician to predict the possibility of upcoming ocular problems in lamellar ichthyosis patients.

Solid facial edema of acne: failure of treatment with isotretinoin.

Solid facial edema of acne is a rare persistent skin condition which occurs as a late complication of acne vulgaris. It is difficult to treat and isotretinoin seems to be the most effective agent. Here we present a 25-year-old man with a facial edema which arose after the complete remission of acne. Treatment with isotretinoin for 4 months was unsuccessful in this case.

Porokeratosis of Mibelli: successful treatment with cryosurgery.

Porokeratosis of Mibelli, a disorder of keratinization, should be treated because of the possibility of development of malignant epithelial tumors on the porokeratotic lesions. Liquid nitrogen cryosurgery is considered to be particularly useful in the treatment of precancerous and benign skin lesions. We aimed to evaluate the efficiency of this method in the treatment of porokeratosis of Mibelli. Eight patients with 20 porokeratotic lesions were treated with spray cryosurgery. Each lesion was frozen for 30 seconds with a spray tip after the keratotic borders were removed conically by sharp dissection. Eighteen of the 20 lesions were healed successfully with slight atrophy in one session. One more session was necessary for the other two lesions. Liquid nitrogen cryosurgery may be considered superior to other destructive methods in the treatment of porokeratosis of Mibelli, with advantages such as simplicity, high cure rates, low cost, short treatment period, and few complications.

Stewart-Bluefarb syndrome: a case report with angiographic findings.

Acroangiodermatitis is a group of benign, angioproliferative cutaneous disease caused by chronic venous insufficiency, acquired or congenital arteriovenous shunts and limb paralysis. Stewart-Bluefarb syndrome is the type of acroangiodermatitis which is associated with a congenital arteriovenous malformation. This is a rare syndrome characterized by cutaneous kaposiform lesions that usually onset at the second decade. In this report, a case of acroangiodermatitis associated with a congenital arteriovenous malformation, which has been diagnosed after 40 years, is described.

Relapsing polychondritis in a child with common variable immunodeficiency.

Common variable immunodeficiency (CVID) is associated with recurrent infections and autoimmunity. The most common autoimmune conditions are idiopathic thrombocytopenic purpura, autoimmune hemolytic anemia, chronic arthritis, and gastrointestinal inflammation. Relapsing polychondritis (RP) is an episodic and progressive systemic inflammatory disease, characterized by auricular chondritis, polyarthritis, nasal, and respiratory tract chondritis. Autoimmunity to cartilage-related components is thought to be involved in its pathogenesis. So far, RP has not been included within many autoimmune conditions that have been reported in patients with either CVID or any other primary immunodeficiency. In this report, a case of CVID with RP and chronic arthritis is presented.

Porokeratosis of Mibelli induced by topical corticosteroid.

BACKGROUND: [corrected] Prorokeratosis of Mibelli is a chronic disorder characterised by slightly atrophic plaques surrounded by keratotic border. METHODS AND RESULTS: A 45-year-old with clobetazole propionate ointment for psoriasis over 15 years developed characteristic lesions of porokeratosis Mibelli on the elbows. Histopathological examination revealed the cornoid lamellae located on the edges of the specimen and psoriasiform acanthosis and a spongiotic pustule formation in the center of the specimen; thus, it was suggested as 'psoriasis encircled by porokeratosis'. CONCLUSIONS: Development of porokeratosis may be explained by the local immunosuppressive effect of the prolonged application of the topical steroid.

Endocrine and metabolic effects of rosiglitazone in non-obese women with polycystic ovary disease.

We hypothesized that the administration of rosiglitazone, an insulin-sensitizing agent of the thiazolidinedione class, would improve the ovulatory dysfunction, hirsutism, hyperandrogenemia, and hyperinsulinemia of polycystic ovary syndrome (PCOS) patients. Forty women with PCOS and impaired glucose tolerance test (IGT) were randomly assigned to the 8-month treatment with rosiglitazone at either 2 mg/day or 4 mg/day. We compared changes in ovulatory function, hirsutism, hormonal levels (total and free testosterone, estradiol, estrone, androstenedione, LH and FSH), and measures of glycemic parameters (fasting and post-challenge levels of glucose and insulin, HOMA-IR, hemoglobin A1c), between the study groups. The patients' baseline characteristics were similar across all treatment arms. Fifteen of 20 women in the 2 mg group and 19 of 20 women in the 4 mg group achieved normal glucose tolerance; 14 of 20 women in the 2 mg group and 17 of 20 women in the 4 mg group achieved ovulatory menses at the end of the study period. The decreases of free testosterone levels were better in the 4 mg group than the 2 mg rosiglitazone group (-1.89+/-0.35 pg/ml vs. -2.21+/-0.39 pg/ml; P<0.01). There were neither any serious adverse events nor any liver enzyme elevations in our study patients during the treatment period. This study demonstrated that rosiglitazone improves the ovulatory dysfunction, hirsutism, hyperandrogenemia, and insulin resistance of PCOS in a dose-related fashion, with minimal adverse effects. This drug may be a good choice for lifetime treatment of patients with PCOS, especially for the ones who failed to show satisfactory results in metformin therapy.