Peyker Temiz

TDP-43 accumulation in inclusion body myopathy muscle suggests a common pathogenic mechanism with frontotemporal dementia

TAR DNA binding protein-43 (TDP-43) is found in ubiquitinated inclusions (UBIs) in some frontotemporal dementias (FTD-U). One form of FTD-U, due to mutations in the valosin containing protein (VCP) gene, occurs with an inclusion body myopathy (IBMPFD). Since IBMPFD brain has TDP-43 in UBIs, we looked for TDP-43 inclusions in IBMPFD muscle. In normal muscle, TDP-43 is present in nuclei. In IBMPFD muscle, TDP-43 is additionally present as large inclusions within UBIs in muscle cytoplasm. TDP-43 inclusions were also found in 78% of sporadic inclusion body myositis (sIBM) muscles. In IBMPFD and sIBM muscle, TDP-43 migrated with an additional band on immunoblot similar to that reported in FTD-U brains. This study adds sIBM and hereditary inclusion body myopathies to the growing list of TDP-43 positive inclusion diseases.

Inflammatory myopathies with mitochondrial pathology and protein aggregates

OBJECTIVES To compare the clinical course and muscle biopsy features of polymyositis with mitochondrial pathology (PM-Mito) to inclusion body myositis (IBM) and steroid-responsive inflammatory myopathies (polymyositis). METHODS We compared clinical, laboratory and myopathologic features in a retrospective study of patients with PM-Mito (23), IBM (26) and polymyositis (12). RESULTS Selective weakness in the quadriceps or finger flexors was common in PM-Mito (62%) and IBM (87%). Weakness progressed more slowly in PM-Mito than in IBM. PM-Mito patients with more rapidly progressive weakness had more cytochrome oxidase negative muscle fibers. There was no history of benefit from corticosteroid treatment in any PM-Mito or IBM patients. B-cell foci were absent in IBM and PM-Mito. LC3, an autophagy marker, and alphaB-crystallin were common in aggregates in PM-Mito and IBM, but not polymyositis. SMI-31 and TDP-43 positive aggregates were common in IBM but not in PM-Mito or polymyositis. beta-amyloid showed no differences in aggregates among the three groups. CONCLUSIONS PM-Mito and IBM may be part of the same disease spectrum. PM-Mito has more slowly progressive weakness than IBM and rarely has TDP-43 or SMI-31 staining aggregates in muscle fibers. The most frequent proteins in aggregates in both PM-Mito and IBM are LC3, an autophagy marker, and alphaB-crystallin. Alterations in autophagic degradation pathways may be a common pathogenic mechanism in PM-Mito and IBM. In pathologically typical polymyositis, staining for mitochondrial enzyme activity, aggregates and B-cells helps to distinguish PM-Mito from inflammatory myopathy syndromes that are more likely to respond to corticosteroid treatment.

Sorafenib-induced erythema multiforme in metastatic renal cell carcinoma

Sorafenib is a new therapeutic agent being used in metastatic renal cell carcinoma, hepatocellular carcinoma, and malignant melanoma. The most frequently seen cutaneous side effects due to sorafenib are erythema, exfoliative dermatitis, acne vulgaris, and flushing. Folliculitis, eczema, and erythema multiforme are other, rare side effects of sorafenib. A 59-year-old man underwent left radical nephrectomy due to renal cell carcinoma 8 months ago, and after the operation he received immunochemotherapy and then sorafenib. On the third day of sorafenib therapy his lesions occurred. His dermatologic examination revealed multiple erythematous papules on his neck, arms, and legs and bullae and iris lesions on his palms and soles. He was diagnosed as having erythema multiforme. In the literature we found only 1 other erythema multiforme case due to sorafenib. We present this interesting case to show and discuss cutaneous side effects of sorafenib, especially erythema multiforme as a very rare cutaneous side effect.

Expression of Nuclear Factor Kappa B and Survivin in Psoriasis

Background and Objective. Suppression of apoptosis has been proposed as a mechanism responsible for epidermal thickness in psoriasis. Survivin is a member of the inhibitor of apoptosis family. Nuclear factor kappa B (NF-κB) is one of the transcriptional factors that regulate many genes affecting apoptosis. The aim of this study was to determine survivin and NF-κB expressions in psoriasis in comparison with normal epidermis. Patients and Methods. Immunohistochemical expressions of survivin and NF-κB were investigated in 41 psoriatic and 21 normal skin samples. Results. Diffuse nuclear survivin expression in all epidermal layers was seen in all of the psoriatic samples. NF-κB expression in different epidermal locations was seen in all of the psoriatic samples. Nuclear staining was positive in 40 psoriasis samples. Similar survivin and NF-κB expressions were observed in normal skin samples. Conclusion. Since similar expressions are seen in both normal and psoriatic epidermis, no important roles for survivin and NF-κB can be attributed in epidermal proliferation and thickness seen in psoriasis.

Acute generalized exanthematous pustulosis with lymphangitis triggered by a spider bite

Acute generalized exanthematous pustulosis (AGEP) is a rare, severe cutaneous reaction pattern that, in the majority (>90%) of cases, is related to administration of medication. It can be seen in both genders and in all ages. The cutaneous manifestations of AGEP are usually seen 1–14 days after drug administration. A 39-year-old woman presented to our outpatient clinic with the complaint of generalized erythema, burning, and rash. She explained that 2 days before presentation a spider bite had occurred on her left forearm, after which she had experienced pain and erythema spreading gradually to the left upper extremity. On her dermatologic examination, she had an indurated necrotic plaque on the left forearm, which had an upward-spreading linear erythema. Additionally, she had diffuse erythema on her body and small pustules over erythematous skin, especially located on the left popliteal fossa and gluteal region. Based on the clinical and histopathologic findings, she was diagnosed as having AGEP. Because there was no drug use in her history, we attributed her AGEP lesions to the spider bite. This case is interesting, because the patient also had lymphangitis. Herein, we present the fifth case reported in the literature of AGEP caused by a spider bite.

Calcinosis cutis on the face

A 46-year-old male patient came to our outpatient clinic with a white lesion on his right cheek. He explained that this lesion occured approximately 25 years ago. There was no family history of similar lesion. Dermatological examination revealed white plaque with an irregular surface 0.5 cm x 1 cm in size on his right cheek, which seemed to be whitewashed [Figure 1]. Skin biopsy was performed from the lesion. Histopathological examination of the specimen revealed calcium deposits in the dermis [Figure 2]. We diagnosed the patient as calcinosis cutis. Laboratory investigations revealed normal calcium and phosphate levels. Other laboratory tests for systemic diseases were also in normal ranges.

The imbalance of enzymatic antioxidants in cholesteatoma

Conclusion. Depletion of enzymatic antioxidants was observed in cholesteatoma. However, a relationship between activity of enzymatic antioxidants and the extent of bone erosion was not found. Objectives. To measure the level of major enzymatic antioxidants in cholesteatoma, and to investigate the relationship between the level of enzymatic antioxidants and the extent of bone erosion. Patients and methods. The cholesteatoma and skin samples were obtained during otologic surgeries. All cases were grouped according to the number of bone erosion sites. Samples were examined biochemically and the levels of enzymatic antioxidants were measured. The results were analyzed statistically. Results. Thirteen patients were included in the study. The mean level of superoxide dismutase in cholesteatoma and skin was 45.87 U/mg and 71.04 U/mg, respectively. When the catalase level was evaluated, the mean level was 5.04 U/g in cholesteatoma and 11.62 U/g in skin. The mean level of glutathione peroxidase in cholesteatoma and skin was 12.13 IU/g and 236.74 IU/g, respectively. All the results of cholesteatoma and skin samples were compared through non-parametric tests and statistically significant differences were found. However, a statistically significant difference between the levels of enzymatic antioxidants and the extent of bone erosion was not observed.

Efficacy of 5% imiquimod cream in a patient with classic Kaposi sarcoma.

BACKGROUND The classic Kaposi sarcoma is most common in the Mediterranean population over 50 years of age and presents with reddish-brown papules and nodules particularly on the lower limbs. Treatment depends on the clinical presentation and extension of lesions. Imiquimod is as an immune response modifier with antiangiogenic activity. MAIN OBSERVATIONS We present a 74-year-old man with classic Kaposi sarcoma who had multiple, small, violaceous papules and nodules on the trunk and extremities with a history of 14 years. He complained particularly from plantar hyperkeratotic painful nodules. Treatment with imiquimod 5% cream under occlusion resulted with almost complete regression within 12 weeks. No local or systemic side effects were observed. CONCLUSIONS Topical imiquimod was a safe and effective therapy in our patient with classic Kaposi sarcoma.

Primary cutaneous CD30-positive anaplastic large cell lymphoma in a 16-year-old girl

The CD30-positive lymphoproliferative disorders represent the second largest group of T-cell lymphomas. Their hallmark is infiltrates of anaplastic CD30+ T cells. These disorders comprise a spectrum of clinically benign lymphomatoid papulosis (LyP) and primary cutaneous anaplastic large cell lymphoma (ALCL). Incidences of LyP and primary cutaneous ALCL peak in people in the fifth and sixth decades of life, respectively, and children are rarely affected.

Acral amelanotic verrucous melanoma: dermoscopic findings.

Acral melanoma is a rare but distinctive subtype of melanoma. It is frequently found in the nonwhite population with dark skin type (Fitzpatrick V and VI). Acral melanoma is the most common type of all cutaneous melanomas (B70%) in these patients. In the white population, its prevalence is 4.5% to 7% of all melanomas. The diagnosis is often delayed, and misdiagnosis is common because its clinical presentation is frequently unusual and there is a higher rate of amelanosis than in other melanoma subtypes. When melanoma is poorly pigmented, there are many conditions in the differential diagnosis such as warts, hemorrhage, ulcers, callous, tinea pedis, and other skin tumors such as squamous cell carcinoma and adnexal tumors.