Dyskeratosis congenita bei einem 40-jährigen Patienten

A 40-year-old patient with a 3-year history of thrombocytopenia was admitted with reticulated and speckled hyper- and hypopigmentations especially on the upper trunk. Aplasia or dystrophy of the fingernails and toenails as well as atresia of the lacrimal ducts were noted. Examination of the oropharynx revealed multiple mucosal leukoplakias and loss of almost all teeth. Based on these observations the diagnosis of X-linked dyskeratosis congenita (Zinsser-Cole-Engman syndrome, OMIM #305000) was made and confirmed by sequencing of the dyskerin 1 (DKC1) gene which revealed a missense mutation in exon 11.     

Case of adult T-cell leukemia/lymphoma manifesting marked purpura

We present a case of a 62-year-old woman with marked purpura, first appearing on both legs, then spreading over the whole body, including the face. At presentation, the patient was thought to have Henoch-Schonlein purpura. However, a skin biopsy from a purpuric lesion revealed prominent infiltrations of atypical lymphocytes into the papillary dermis and marked extravasation of erythrocytes through the epidermis and upper dermis. Antibody to human T-lymphotropic virus type 1 (HTLV-1) was present in the serum and samples from skin lesions revealed HTLV-1 proviral DNA integration, as well as a clonal T-cell receptor Cbeta1 gene rearrangement. We therefore diagnosed this case as adult T-cell leukemia/lymphoma (ATL), and the purpuric lesions as ATL-specific. Soon after the initiation of chemotherapy, these purpuric lesions began to resolve with pigmentation.     

Systemic lupus erythematosus complicated with protein-losing enteropathy: a case report and review of the published works

A 45-year-old man was referred to our hospital with a history of multiple erythematous skin lesions of several months' duration. Blood examination revealed extreme hypoproteinemia and hypoalbuminemia, as well as the presence of antinuclear antibodies. A skin biopsy specimen showed liquefaction degeneration at the dermoepidermal junction and dense lymphocyte and neutrophil infiltration around the vessels and appendages in the upper and middle dermis. Chest X-ray and computed tomography showed a pleural effusion and thoracic paracentesis revealed a mononuclear cell-dominant cell infiltration, suggestive of serositis. Technetium-99m ((99m)Tc)-labeled human serum albumin scintigraphy and α(1)-antitrypsin clearance revealed protein leakage along the digestive tracts from the stomach to the jejunum. From the above findings, the patient was diagnosed with systemic lupus erythematosus (SLE) complicated by protein-losing enteropathy (PLE). Treatment with oral prednisolone significantly improved his clinical symptoms and hypoalbuminemia. This case highlighted the utility of (99m)Tc-labeled human serum albumin scintigraphy and α(1)-antitrypsin clearance in the diagnosis of PLE. We also present a published work review on PLE associated with connective tissue disease revealing a relatively higher prevalence in patients of Asian ethnicity, including Japanese.     

球孢枝孢致皮肤暗色丝孢霉病一例

患者男,53岁,农民。10年前右手背出现一小疖肿,外用红霉素软膏2周后治愈。1个月后右手背出现一蚕豆大皮肤溃疡,经抗感染治疗后愈合,但皮损处皮肤增厚,长期外用皮炎平乳膏未见明显好转。2006年3月26日就诊。发病期间无发热。无糖尿病、结核病等慢性病及外伤史。体检：右手背皮肤见一不规则疣状斑块,约2.5 cm × 4 cm大小,有少许渗液。其他部位皮肤未见异常。口腔分泌物及尿沉渣真菌检查均为阴性。皮损KOH镜检见棕色孢子,沙氏葡萄糖琼脂培养基培养出局限、绒状、墨绿色菌落,镜下见枝孢产生具分枝的球形分生孢子链。DNA序列分析显示,该菌株26S rDNA D1/D2序列与GeneBank中的球孢枝孢（AB100654）相差2个碱基,ITS序列与球孢枝孢（AM176719）相同,与球孢枝孢（AY625063）相差5个碱基。结合上述发现及微量培养等结果,该菌株鉴定为球孢枝孢。皮损组织HE染色显示肉芽肿相,PAS染色见棕色孢子,结合真菌学检查结果,诊断为皮肤暗色丝孢霉病。体外药敏试验显示该菌株对伊曲康唑敏感。给予患者口服伊曲康唑0.2 g/d,连续8周,皮损明显消退,但2个月后失访。     

Dermatomyositis and acquired ichthyosis as paraneoplastic manifestations of ovarian tumor

Case 1 A 37-year-old white woman was seen at the Dermatology Clinic presenting muscle weakness of the pelvic and scapular girdles, as well as a violaceous erythema and periorbital infiltration (heliotropium) and erythematous-violaceous lesions on the dorsum of the finger joints, with periungual telangiectasia. A diagnosis of dermatomyositis was confirmed and treatment with prednisone, 1 mg/kg per day, was started, with improvement.
One year and two months later she presented ascites, bilateral pleural effusion, and a 7-kg weight loss. Cytology of the ascitic fluid revealed cells compatible with adenocarclnoma. Exploratory laparotomy demonstrated peritoneal carcinomatosis, and an implant biopsy confirmed a moderately differentiated adenocarcinoma of the ovary of the endometriold type. The patient died 1 year and 4 months after the diagnosis of dermatomyositis (Fig. 1 and Table 1).
Case 2 An 8-year-old white girl was seen at the Dermatology Clinic presenting generalized ichthyotic skin of a brovi/nish color, perilabial and palmo-plantar fissures of 5 months duration, and hair fall. For the last 2 months, she had been presenting daily fever (38°C) and lack of appetite, and had lost 7 kg.
Abdominal ultrasound revealed a large pelvic mass (9 × 8 × 7 cm) located in a small basin, with possible right renal invasion, as well as periaortic and pericaval adenomegaly, findings that were later confirmed by computerized tomography. Radiologic examinations of the thorax, skull, spine, and long bones were normal. Exploratory laparotomy confirmed the presence of a dysgerminoma of the right ovary as determined by biopsy (Fig. 2).
Chemotherapy was started (carboplatin, bleomycin, and vinblastine) and an abdominal ultrasound taken 1 5 days later showed a 67.5% reduction of the pelvic mass, as well as reduction of rectoperitoneal adenomegaly.     

Contact allergy to ophthalmic dipivalyl epinephrine hydrochloride: demonstration by patch testing

A patient presented with a 3-month history of conjunctivitis and periocular eczema. He had a 3-year history of glaucoma and was being treated with 3 different locally applied eyedrops (Timoptic (timolol maleate) ophthalmic solution 0.25%, Pilocar (pilocarpine) ophthalmic solution 1%. and Propine (dipivalyl epinephrine hydrochloride) ophthalmic solution 0.1%). Patch testing with all 3 undiluted eyedrop solutions revealed a reaction only to Propine eyedrops. Patch testing to the individual components of Propine eyedrops revealed an allergic reaction to 0.5%, dipivalyl epinephrine hydrochloride that was apparent on the 2nd patch test reading. After discontinuing the Propine eyedrops, the conjunctivitis as well as the periocular dermatitis resolved, proving that the positive patch tests were relevant to both. It was reported that re-exposure to dipivalyl epinephrine hydrochloride by intra-ocular challenge was necessary to diagnose this allergy. This is the first demonstration of dipivalyl epinephrine hydrochloride allergy by patch testing. Since the 1st patch test reading (2 days) was weak. 2nd patch test (4 days) readings may be important in diagnosing this allergy by patch testing.     

Cutaneous neoplasms composed of melanoma and carcinoma: A rare but important diagnostic pitfall and review of the literature

We report two cases of combined cutaneous tumors composed of melanoma and carcinoma. The first tumor presented as a 5-mm pink-blue macule over the right zygomatic arch in an 85-year-old man. Shave biopsy and immunohistochemical studies revealed that the tumor was composed of melanoma (highlighted by SOX10 and MART-1, with high Ki-67 proliferative index) intermixed with nodular basal cell carcinoma (highlighted by pan-cytokeratin and Ber-EP4). The neoplastic melanocytes were confined to the basal cell carcinoma nodules, and a diagnosis of combined melanoma in situ and basal cell carcinoma was rendered. After therapeutic excision, the patient was disease-free at 9 months after the initial diagnosis. The second tumor presented as a 6-mm pink-brown crusted papule on the right forehead in an 89-year-old man. Shave biopsy and immunohistochemical studies revealed that the tumor was composed of malignant melanoma (MM) (highlighted by S100 and MART-1) intermixed with squamous cell carcinoma (SCC) (highlighted by cytokeratin and p63), and a diagnosis of combined MM-SCC was rendered. These two cases highlight the importance of recognizing these rare types of melanocytic-epithelial cutaneous neoplasms to arrive at an accurate diagnosis that may inform appropriate disease stage and therapy.     

A Case of pemphigus foliaceus which occurred after five years of remission from pemphigus vulgaris

A 77-year-old Japanese female developed pemphigus foliaceus (PF) after 5 years of remission from pemphigus vulgaris (PV). The patient had painful erosions in her mouth and flaccid blisters of the skin and was diagnosed as having PV, which responded well to corticosteroid treatment. She was then free from any lesion of PV for 5 years with a low dose of corticosteroid. Then she developed scaly erythematous lesions on the skin and was diagnosed as suffering from PF. Enzyme-linked immunosorbent assay (ELISA) using recombinant desmoglein 1 (Dsg-1) and Dsg-3 revealed that she had anti-Dsg-3 IgG in the PV stage, no antibodies during remission and anti-Dsg-1 IgG in the PF stage. These findings indicate that the target antigen was shifted from Dsg-3 to Dsg-1 along with the phenotype after a 5-year interval in this patient.     

Development of thoracic sarcoid reactions associated with complete response to anti-PD-1 therapy in a patient with advanced cutaneous squamous cell carcinoma

In patients with advanced cutaneous squamous cell carcinoma (cSCC), positive efficacy data were reported for anti-PD-1 antibodies. However, anti-PD-1 treatment is associated with a wide range of immune-related adverse events (irAEs). Here, we report on a 78-year-old woman with a huge cSCC on the right cheek spanning from the temporal to the cervical region with evidence for infiltration of the parotid gland, right masseter muscle and right auditory canal. Ultrasound revealed cervical, submandibular and supraclavicular lymph node metastases on patient’s right side. On the basis of a medical hardship application, treatment with pembrolizumab was initiated. After two applications, a dramatic regression of the tumour was observed. At this point, the patient was switched to cemiplimab, which, in the meantime, had become available in Germany. After 3 months on cemiplimab, the tumour-related ulcer on the right cheek showed almost complete regression and all previously affected lymph nodes displayed no evidence for malignancy. Thoracic computed tomography (CT) scans revealed enlarged mediastinal and bilateral hilar lymph nodes assessed as primarily reactive. Three months later, however, mediastinal and bilateral hilar lymph nodes further increased in size, accompanied by radiological alterations of the lung parenchyma. Lymph node biopsies revealed sarcoid reactions (SRs) including fibrotic non-caseating epitheloid cell granulomas surrounded by lymphocytes. Since the patient did not display any clinical symptoms, cemiplimab treatment was continued following a 4-week break. Three months later, CT showed significant regression of the described enlarged lymph nodes and parenchymal lung changes. Twenty months after anti-PD-1 treatment, the patient was still in complete remission. In conclusion, we describe, for the first time, the case of a patient with advanced cSCC who developed disseminated thoracic SRs which were associated with dramatic regression of tumour masses. Thus, as with other irAEs, development of SRs might be indicative of an anti-tumour response to anti-PD-1 therapy.     

Expression of B7-1 costimulatory molecules in patients with multibacillary leprosy and reactional states

BACKGROUND: The expression of B7 as a costimulatory molecule on the surface of antigen-presenting cells such as macrophages and on dendritic cells characterizes the efficiency of the cell-mediated immune response. AIMS: Our purpose was to evaluate B7-1 expression in peripheral blood mononuclear cells (PBMCs) immediately after cell isolation ('spontaneous' B7 expression), and in inflammatory cells from cutaneous lesions of patients with multibacillary leprosy (MB-L) without and during the reactional states of erythema nodosum leprosum (ENL) or reversal reaction (RR). METHODS: Peripheral blood samples and skin biopsies of eight patients without (MB-L) and with reactional episodes (ENL and RR) were studied using antibodies against B7-1, CD1b, DR and CD14 in flow-cytometry and immunohistochemistry experiments. RESULTS: The flow-cytometry studies (mean +/- SD% of fluorescent cells) revealed significant B7-1 expression on PBMCs isolated from patients with ENL (8.0 +/- 0.6%) and RR (15.0 +/- 1.4%) compared with that observed for patients with MB-L (0.4 +/- 0.2%). Similar results were observed for cutaneous lesions of these patients by immunohistochemical assays. One patient studied before and during ENL revealed weak B7 expression before the reactional episode (0.3% of cells) compared with the marked level of B7-expressing cells detected during ENL (8.5% fluorescent cells). Interestingly, an even higher B7 expression (15% of cells) was observed in patients with RR. CONCLUSIONS: Our results strongly suggest that B7 expression precedes reactional episodes in MB-L, which could be related to the acquisition of effective immunity to Mycobacterium leprae during reactional episodes in leprosy. We propose B7 expression as a marker of CMI response in reactional episodes in leprosy.     

HLA Class I and II Alleles and Susceptibility to Generalized Pustular Psoriasis: Significant Associations with HLA-Cw1 and HLA-DQB1*0303

HLA alleles in generalized pustular psoriasis (GPP) were investigated to clarify the etiology and/or pathogenesis of this disease. Not only serological typing of HLA class I and II antigens but also genotyping of HLA class II alleles were carried out in twenty-six unrelated Japanese patients with GPP. These patients were classified according to their history of psoriasis vulgaris (PV). Serological typing revealed a significantly high incidence of HLA-Cw1 (Pc=0.04) in the patients as compared with Japanese healthy controls. The frequency of HLA-B46 was particularly high in the patients with GPP and a previous history of PV. Genotyping of HLA class II alleles showed a highly significant increase in HLA-DQB1*0303 (Pc=0.01) in the patients vs. the healthy controls. In particular, HLA-DQB1*0303 was significantly more frequent in the patients with no prior history of PV than in those with a history of PV. Analysis on linkage disequilibrium showed remarkably different patterns for HLA class II haplotypes between the patients and the healthy controls. Based on the comparative analysis among the amino acid sequences of the β1-domain of the HLA-DQB1*03 alleles, proline at residue 55 was suggested to be important as a common amino acid for determination of the susceptibility to GPP. These results revealed not only an association between the etiology and/or pathogenesis of GPP and HLA, but also different mechanisms of the immune response between the patients with GPP and PV.     

Vitamin D3 upregulated protein 1 (VDUP1) is a regulator for redox signaling and stress-mediated diseases

Vitamin D(3) upregulated protein 1 (VDUP1) is a 46-kDa multifunctional protein, initially isolated in HL-60 cells as a protein of which expression is upregulated by vitamin D(3) administration. Subsequently, it was identified independently by investigators from diverse scientific backgrounds as a thioredoxin binding protein that negatively regulates the expression and the activity of thioredoxin, and is thus involved in redox regulation. Further studies have revealed that VDUP1 plays multiple roles in a wide range of cellular processes such as proliferation or apoptosis. Recently, it has been reported that VDUP1 is also involved in the immune system via positive regulation of natural killer development. In addition, VDUP1 has been revealed to be associated with the fatty acid utilization. In the present review, we discuss the novel aspects of VDUP1 function as well as the historical background of VDUP1. Future studies will explore the diagnostic and therapeutic potential of modulating the function of VDUP1 in vivo.     

A Case of Pemphigus Herpetiformis with Only Immunoglobulin G Anti-Desmocollin 3 Antibodies

Pemphigus represents a group of autoimmune blistering diseases caused by autoantibodies against desmogleins (Dsgs), a class of desmosomal cadherins. Recently, several pemphigus patients only with desmocollin (Dsc) 3-specific antibodies have been reported. Here, we report a case of pemphigus herpetiformis (PH), where only anti-Dsc3-specific antibodies but not anti-Dsg antibodies were detected. A 76-year-old woman presented with a 3-year history of blister formation. Physical examination revealed pruritic erythemas with vesicles on the trunk and legs, but no lesions of the oral mucosa. A skin biopsy specimen revealed intraepidermal blister containing neutrophils, eosinophils, and lymphocytes. Direct immunofluorescence (IF) showed immunoglobulin G (IgG) and complement 3 (C3) depositions on the keratinocyte cell surfaces. Indirect IF showed IgG anti-keratinocyte cell surface antibodies. These findings hinted at a diagnosis of pemphigus. However, repeated enzyme-linked immunosorbent assays (ELISAs) for both anti-Dsg1 and 3 antibodies proved to be negative. Immunoblotting of normal human epidermal extracts revealed Dsc antibodies, and recently established ELISAs using human Dsc1-Dsc3 recombinantly expressed in mammalian cells detected anti-Dsc3 antibodies. Based on these clinical, histopathological, and immunological findings, the patient was diagnosed as PH with only anti-Dsc3 antibodies. Treatment with corticosteroid prednisolone and steroid-sparing agent dapsone accomplished complete clinical remission of the patient.     

Kimura's disease

A 40-year-old white Caucasian man presented with a 6-month history of a 1.5 × 1.5 cm nodular lesion on his left arm. No history of trauma preceeded the lesion and the patient was in good general health.
Dermatologic examination revealed a solitary, red, painless nodule located on the left arm (Fig. 1). Histopathologic examination of punch biopsy revealed lymphoid follicles, some of which had active germinal centers in the deep dermis and subcutaneous tissue. Mixed infiltration of lymphocytes, plasma cells and many eosinophils were present in the interfollicular region. Infiltration of the germinal centers by eosinophils, causing partial destruction, was observed (Fig. 2A). There was also proliferation of thin-walled small vessels and fibrosis in some parts of the interfollicular areas (Fig. 2B). Although Kimura's disease (KD) and angiolymphoid hyperplasia with eosinophilia (ALHE) were considered in the differential diagnosis, it was diagnosed as KD based on these histologic features. Further laboratory examinations were performed. Serum IgE was normal and peripheral eosinophilia was absent.
The lesion regressed after biopsy. Complete healing was achieved with intralesional corticosteroid (triamcinolone acetonide) treatment.     

A novel topical combination of minoxidil and spironolactone for androgenetic alopecia: Clinical,histopathological, and physicochemical study

Topical minoxidil 5% are effective in androgenetic alopecia (AGA). Spironolactone acts as an androgen antagonist by competitively blocking androgen receptors. Studying the effect of topical minoxidil 5% gel and spironolactone gel 1% in management of AGA. The study includes 60 patients diagnosed as AGA; (group I): treated with topical minoxidil gel 5%, (group II): with topical spironolactone gel 1% and group (III) treated with combined minoxidil 5% and spironolactone 1% gel. All patients were followed up monthly throughout the treatment period. Scalp biopsy was taken before and after 12 months. In group I, the clinical response was in 90% of patients with variable degrees in improvement, in group II, the clinical response was in 80% of patients, meanwhile, in group III the clinical response was in all patients (100%). Histopathological examination of skin biopsy after treatment revealed significant increase in anagen hair on the other hand, both telogen and vellus hair was significantly decreased meanwhile, the T/V ratio was significantly increased. The results of this work revealed that topical minoxidil gel 5% and topical spironolactone gel 1% were effective in treatment of AGA, while the combination of two agents was better in treatment.     

亲毛囊性蕈样肉芽肿伴嗜酸粒细胞增多一例

患者男,69岁。3年来,头、躯干和四肢出现散在红斑、毛囊性丘疹及痤疮样皮损（如粟丘疹、囊肿等）和脱发,病程中伴外周血嗜酸粒细胞增多。皮损组织病理检查示真皮内灶性慢性炎细胞浸润伴毛细血管增生,毛囊周围慢性炎细胞浸润伴血管增生,伴少许嗜酸粒细胞,考虑为毛囊炎,予抗组胺药和抗生素治疗后皮损炎症消退,瘙痒减轻。3个月后,枕部出现斑块伴脱发,组织病理检查示真皮内密集淋巴样细胞、嗜酸粒细胞浸润,毛囊周围大量淋巴样细胞浸润伴较多嗜酸粒细胞,可见不典型淋巴细胞,部分侵入毛囊,毛囊上皮黏液样变性。阿新蓝染色阳性。免疫组化染色：CD20、CD79a、EB病毒（EBV）、CD56、磷酸葡萄糖变位酶-1（PGM-1）、髓过氧化物酶（MPO）、CD7、抗角蛋白单克隆抗体AE1/AE3均阴性,异形细胞CD3、CD4、CD5、CD2、CD43、泛素羧基末端水解酶-L1（UCHL-1）均阳性。T细胞受体基因重排结果为阴性。诊断：亲毛囊性蕈样肉芽肿。予光化学疗法（PUVA）联合阿维A治疗,仍有新发皮损,目前患者在随访中。     

Environmental risk factors in endemic pemphigus foliaceus (fogo selvagem)

An ongoing sero-epidemiological study of the Terena reservation of Limao Verde, known to have a high prevalence and incidence of FS, has revealed important information about this autoimmune disease. During surveillance of this population of approximately 1,200, which began in 1994, we documented 43 FS cases and studied the transition from the normal state to the disease state in several of these individuals. Furthermore, we established that FS patients as well as a large number of normal individuals on the reservation possess anti-dsg1 autoantibodies. The following interesting observations were made: (1) the ectodomain of dsg1 contains epitopes recognized by both autoantibodies and T cells from FS patients; (2) pathogenic anti-dsg1 autoantibodies in FS belong to the IgG4 subclass; (3) nonpathogenic anti-dsg1 autoantibodies of the IgG1 subclass were detected in normal individuals from Limao Verde and in patients in the preclinical stage of the disease; (4) anti-dsg1 autoantibodies from normal individuals and patients in the preclinical stage of FS recognize the EC5 domain of dsg1, whereas pathogenic anti-dsg1 autoantibodies bind the EC1/EC2 domains; (5) houses of FS patients are rustic, with thatched roofs and walls and dirt floors; (6) there was a high frequency of hematophagous insects (bedbugs and kissing bugs) in the houses of FS patients; (7) previous studies revealed that the predominant black fly on this reservation belongs to the species Simunlium nigrimanum. These findings suggest that the environmental antigen(s) triggering the autoimmune response in FS may be linked to exposure to hematophagous insects.     

伴食道大疱的获得性大疱性表皮松解症合并获得性血友病1例国内首报

目的报告1例伴食道大疱的获得性大疱性表皮松解症合并获得性血友病。方法对其临床、胃镜、血液病学检查、皮肤组织病理和直接免疫荧光进行研究。结果胃镜检查示食道内多发大小不等水疱。血液病学检查示活化部分凝血活酶时间(APTT)88.7s(正常值:20.90~34.60s);第Ⅷ因子活性6.9%(正常值:50.0%~150.0%);第Ⅷ因子抑制物滴度312B.U./ml(正常:0)。组织病理检查:表皮下水疱。1M氯化钠裂解皮肤直接免疫荧光检查示基底膜带真皮侧IgG呈线状沉积。结论此为一罕见的病例。