Lesional activation of Tc 17 cells in Behçet disease and psoriasis supports HLA class I-mediated autoimmune responses.

BACKGROUND: Behçet disease (BD) presents with lymphocytic and neutrophilic vasculitis of unknown aetiology. HLA-B*51, the endoplasmic reticulum aminopeptidase 1 (ERAP1), and interleukin 23 receptor (IL23R)/IL12R are genetic risk factors. IL-23 regulates IL-17A, which controls the recruitment and activation of neutrophils. OBJECTIVES: To determine pathological changes in BD skin lesions related to the complex genetic predisposition. METHODS: We characterized the expression of IL-17A and IL-23A in various cell types by immunohistological double staining of sections from papulopustular skin lesions of acute attacks of BD and psoriasis vulgaris lesions, another HLA-class I-associated T-cell-mediated autoimmune disease in which excessive T-cell-derived IL-17A production promotes neutrophil activation. RESULTS: We found that in BD lesions, as in psoriasis, actively expanding CD8+ T cells were the predominant source of IL-17A. IL-17A+ CD8+ T (Tc 17) cells outnumbered infiltrating IL-17A+ CD4+ T cells. Unlike the epidermal localization of CD8+ T cells in psoriasis, Tc 17 cells in BD lesions mainly infiltrated the perivascular tissue and the blood vessel walls of dermis and subcutaneous tissue. They co-localised with a marked IL-23A expression by CD11c+ dendritic cells and CD68+ macrophages. IL-17A expression was associated with extensive recruitment of neutrophils around blood vessels that formed neutrophil extracellular traps (NETs). CONCLUSIONS: In BD, the genetic predisposition may mediate antigen-specific activation and differentiation of a Tc 17 response, possibly targeting endothelial (auto)antigens. Neutrophils recruited by IL-17A in this process may enhance tissue damage by extensive NET formation (NETosis). Thus, the IL-23/IL-17 axis presumably controls neutrophilic inflammation in BD vasculitis in the context of a predominant antigen-specific CD8+ T-cell response.

Ulcerative IgA vasculitis in the setting of warfarin therapy.

Henoch-Schönlein purpura (HSP) is a small vessel vasculitis characterized by the presence of vascular immunoglobulin A deposition that usually presents as non-thrombocytopenic palpable purpura. It primarily affects children and is less common in adults. The incidence of hemorrhagic necrotic skin lesions increases with age, similarly to renal involvement. Warfarin is a widely used oral anticoagulant drug that has rarely been associated with leukocytoclastic vasculitis and allergic interstitial nephritis. We report a patient with HSP who presented with cutaneous ulcerative plaques and proteinuria in the setting of warfarin therapy. We would like to raise the awareness of this potential adverse effect of warfarin for prompt diagnosis.

Cardiomyopathy with alopecia and palmoplantar keratoderma (CAPK) is caused by a JUP mutation.

Inherited desmosomal cardiocutaneous syndromes are characterized by the quartet of woolly hair, palmoplantar keratoderma (PPK), skin fragility and cardiac abnormalities, which are caused by mutations in genes coding for desmosomal proteins. We describe a previously unrecognized autosomal recessive syndrome in a family with arrhythmogenic right ventricular cardiomyopathy associated with alopecia and PPK (named CAPK). Genetic investigation of the family led us to find a homozygous disease-causing mutation, p.R265H, in JUP which encodes plakoglobin, a well-described member of the desmosome complex. This study expands the clinical spectrum of disorders associated with germline mutations affecting desmosomal proteins by describing a novel phenotype.

Black hairy tongue after allogeneic stem cell transplantation: an unrecognized cutaneous presentation of graft-versus-host disease.

Black hairy tongue (BHT) is an unusual condition in adults characterized by marked accumulation of keratin on the dorsum of the tongue, resulting in a hair-like appearance. Herein, we have described 15 patients developing BHT after allogeneic stem cell transplantation (allo-SCT). BHT was generally accompanied by other cutaneous manifestations of cutaneous graft-versus-host disease (GVHD) or a precursor of GVHD. Our experience in this series emphasized that histopathologic evaluation is required for seemingly harmless eruptions like BHT in the posttransplantation period. Given the important prognostic implications of GVHD, physicians should be careful when confronted with BHT.

Dermatoscopy of flat pigmented facial lesions: diagnostic challenge between pigmented actinic keratosis and lentigo maligna.

BACKGROUND: The similarity between clinical pictures of pigmented actinic keratosis (PAK) and lentigo maligna (LM) is well known. OBJECTIVES: To investigate the frequency of dermatoscopic findings suggestive of LM/lentigo maligna melanoma (LMM) in the other facial pigmented skin lesions (FPSL) and to assess the distinguishing dermoscopic criteria of PAK and LM. METHODS: Eighty-nine FPSL were evaluated with conventional dermatoscopy. The lesions showing one or more dermatoscopic features considered as specific patterns for the diagnosis of LM/LMM, mainly slate-grey to black dots and globules, slate-grey areas, annular-granular pattern, asymmetrical pigmented follicular openings, black blotches, rhomboidal structures, hyperpigmented rim of follicular openings, slate-grey streaks and dark streaks, were included in the study selectively. RESULTS: PAK was diagnosed in 67, LM or LMM in 20 and lichen planus-like keratosis in two lesions, histopathologically. Eleven essential dermatoscopic features were observed in facial PAK: slate-grey dots (70%); annular-granular pattern (39%); rhomboidal structures (36%); pseudonetwork (36%); black globules (34%); slate-grey globules (33%); black dots (30%); asymmetrical pigmented follicular openings (25%); hyperpigmented rim of follicular openings (21%); slate-grey areas (18%); and streaks (3%). CONCLUSIONS: PAK has a striking similarity to LM/LMM in clinical and dermatoscopic features, thus representing a diagnostic challange. All dermatoscopic findings except black blotches were observed in PAK. As dermatoscopic diagnosis of a pigmented skin lesion cannot be based on the presence of a single criterion, we may conclude that histopathology still remains the gold standard for correct diagnosis.

Postirradiation linear morphoea.

Postirradiation morphoea is an uncommon side-effect of radiotherapy. We report a 74-year-old woman who was treated with radiotherapy for endometrial carcinoma. About 3.5 years after the first dose of radiotherapy, the patient developed linear morphoea starting from the radiation port and affecting distant, nonirradiated skin. Lesions of radiation-induced morphoea are generally described as well-demarcated, indurated plaques with varying amounts of associated erythema; however, there is no previous publication of unilateral band-like distribution of morphoea associated with radiotherapy, to our knowledge.

Intramedullary mature cystic teratoma of the conus medullaris. A case report.

Intramedullary teratoma is extremely rare and to our knowledge has been reported in only nine cases in the literature. We report a case of mature cystic teratoma of the conus medullaris. The case was diagnosed by magnetic resonance imaging and operated with microneurosurgical techniques.

Behçet's disease-like presentation of bullous pyoderma gangrenosum associated with Crohn's disease.

A 47-year-old woman presented with a 2-month history of generalized arthralgia and a 10-day history of oral aphthous ulcers. After hospitalization, papulopustular lesions and perianal ulcerations developed. Pathergy test was positive and ophthalmological examination was normal. The presence of oral aphthous ulcers, genital ulcerations, papulopustular lesions and arthralgia, and the positive pathergy test suggested the diagnosis of Behçet's disease (BD). In a few days, positive pathergy reactions and papulopustular lesions evolved into bullous lesions, which were diagnosed dermatopathologically as pyoderma gangrenosum. Two days after the presentation of papulopustular lesions, the patient experienced diarrhoea accompanied by bloody stools and mucus. Histopathological examination of biopsy specimens showed no vasculitis but revealed findings suggestive of Crohn's disease. The patient responded well to treatment with systemic steroids and 5-aminosalicylic acid. Our case demonstrates that the differential diagnosis of BD and inflammatory bowel disease may be perplexing and that these two diseases may be closely related.

Granuloma annulare on herpes zoster scars in a Hodgkin's disease patient following autologous peripheral stem cell transplantation.

Various cutaneous lesions including granulomatous reactions may occur at sites of resolved herpes zoster infection. A 46-year-old man with Hodgkin's disease developed localized granuloma annulare lesions on herpes zoster scars 3 months after allogeneic peripheral stem cell transplantation. This is the first case of granuloma annulare localized on herpes zoster scars that developed following peripheral stem cell transplantation.

Lamivudine vs lamivudine and interferon combination treatment of HBeAg(-) chronic hepatitis B.

To determine whether combination treatment of HBeAg(-) chronic hepatitis B is beneficial we studied 78 patients with HBeAg(-), HBV DNA-positive chronic hepatitis B who were randomized to lamivudine, 100 mg, qd, for 12 months or lamivudine-interferon (9 MU, t.i.w.) in combination. In the combination arm, 2 months of lamivudine treatment preceded 10 months of combination treatment. Biochemical, virologic and histologic responses were assessed at the end of treatment, after six and a median 27 months of drug-free follow-up (short- and long-term follow-up, respectively). Virologic response was defined as undetectable HBV DNA with a hybridization assay and biochemical response as normal alanine aminotransferase (ALT). Change in HBV DNA was also assessed by real-time polymerase chain reaction (PCR). Presence of YMDD mutants at the end of treatment was investigated with a line probe assay. Both treatment regimes led to a median 2 log decline in HBV DNA levels. Virologic end of treatment responses were 90 and 92% with mono- and combination treatment, respectively. Corresponding virologic responses at short- and long-term follow-up were 59 and 54%, and 27 and 25%, respectively. Patients having a baseline HBV DNA value > or =200 pg/mL were more likely to relapse within 6 months off therapy than those patients with a baseline HBV DNA level <200 pg/mL (P = 0.041). YMDD mutants were observed in 53% of patients receiving lamivudine compared with 24% of patients receiving the combination regime (P = 0.017). In conclusion, efficacy of combination treatment is similar to lamivudine monotherapy. However, combination treatment decreases the development of YMDD mutant strains compared with lamivudine monotherapy.

Airway inflammation in nasal polyposis: immunopathological aspects of relation to asthma.

BACKGROUND: Nasal polyposis (NP) is a chronic inflammatory disorder of the upper respiratory tract, which is often coexist with asthma. However, the pathogenesis of especially in patients with NP is still a matter of debate. OBJECTIVE: To better understand the immunopathologic mechanism involved in this relationship, we investigated the inflammatory cell profiles in bronchial and nasal tissues of patients with NP alone and with concomitant asthma. METHODS: Seventeen patients with NP (six male, 11 female, age range: 19-63, mean age: 38.29+/-13.27 years) were selected for the study. Subjects were divided into two groups based on the presence of asthma or bronchial hyper-responsiveness (BHR). NP without BHR (Group 1) (n=8), NP and asthma or BHR (Group 2) (n=9). All patients underwent atopy evaluation including detailed history, skin prick test (SPT), total and specific IgE determination in sera. None of the subjects had taken inhaled, nasal or oral corticosteroids for at least 1 month before the study. Respiratory symptoms of asthmatic patients were controlled with only short acting beta(2)-agonist inhaler drugs as needed. NP tissue, nasal and bronchial mucosa biopsies were taken from all patients using fiberoptic endoscopy. CD3, CD8, CD16, CD68, AA1 (mast cell tryptase), human leucocyte antigen-DR (HLA-DR) and eosinophil peroxidase (EPO) expressing cells in specimens were determined by immunohistochemical methods. Positively staining inflammatory cell types were counted. Subepithelial lamina propria and periglandular areas were separately evaluated. RESULTS: No significant difference was found in polyp tissue, nasal and bronchial CD3(+), CD8(+), CD16(+), CD68(+), AA1(+), HLA-DR(+) and EPO(+) positive cells between groups. There were significantly higher numbers of CD8(+), CD16(+), HLA-DR(+), EPO(+) cells in the polyp tissue and nasal mucosa vs. the bronchial mucosa in all groups (P<0.05). However, CD8(+) cells were significantly increased in the polyp tissue and bronchial mucosa of patients with NP alone when compared with the patients with both asthma and NP (P<0.05). CD3(+), CD68(+) and CD16(+) cell counts were tended to be higher within the nasal polyp tissue of patients with isolated NP compared with counts within nasal and bronchial mucosa of patients with NP and asthma. Also, patients with isolated NP showed more HLA-DR(+) cells in the nasal polyp tissue and nasal mucosa than those of patients with NP and asthma. Immunoreactivity for EPO(+) eosinophils within the nasal and bronchial mucosa was more prominent in patients with NP and asthma compared with patients with NP alone. The number of EPO(+) eosinophils within the polyp tissue, nasal and bronchial mucosa was higher in the skin prick test negative (SPT -ve) group than the SPT positive (SPT +ve) ones. CONCLUSIONS: Our results demonstrate that infiltration of inflammatory cells in the nasal and the lower airways do not remarkably differ between patients with NP alone who has no evidence of BHR and asthmatic patients with NP. However, patients with SPT-ve NP reveal more intense eosinophilic inflammation in the entire respiratory mucosa.

Retrorectal dermoid cyst in a male adult: case report.

We describe a 48-year-old male patient who presented with rectal fullness and pain. Magnetic resonance imaging (MRI) and computed tomographic studies revealed a noncalcified, unilocular, cystic mass lesion with well-defined borders. On MRI nondependent fat spheres were detected inside the cyst. The same pattern has been described in dermoid cyst of the ovary. We suggest that this MRI pattern is specific to dermoid cysts.

Famciclovir treatment of chronic delta hepatitis.

BACKGROUND/AIMS: Interferon is the only established therapy for chronic delta hepatitis and alternative treatment options are an urgent need. Since successful treatment of a case of post-transplant delta hepatitis with the nucleoside analogue famciclovir had been reported, a pilot study was undertaken to evaluate the use of famciclovir in the treatment of chronic delta hepatitis. METHODS: A total of 15 adult patients, 13 men, two women, ages 20-52 years, with chronic delta hepatitis were treated with famciclovir, 500 mg, three times a day for 6 months and were then followed-up for 6 months posttreatment. All patients had compensated chronic liver disease, elevated liver enzymes and were hepatitis delta virus (HDV) RNA positive by polymerase chain reaction at baseline. Patients were monitored and tested for HBsAg, hepatitis B virus (HBV) DNA and HDV RNA levels. Liver biopsies were obtained before starting famciclovir and within 1 month of completion of treatment. RESULTS: HBV DNA levels decreased in nine of the 15 patients and levels rose again after treatment (P<0.05). Famciclovir had no effect on alanine aminotransferase (ALT) and HBsAg levels or on serum HDV RNA and overall, there was no improvement in liver histology. CONCLUSIONS: Treatment of chronic delta hepatitis with famciclovir has no effect on disease activity and HDV RNA levels.

Penile epithelioid sarcoma.

Epithelioid sarcoma is a rare mesenchymal neoplasm. We had the opportunity to report a case of epithelioid sarcoma of the penis.