Clinical characteristics, quality of life and risk factors for severity in palmoplantar pustulosis: a cross-sectional, multicentre study of 263 patients.

BACKGROUND: Palmoplantar pustulosis (PPP) is a rare, chronic, inflammatory skin disease characterized by sterile pustules on palmar or plantar areas. Data on PPP are scarce. AIM: To investigate the clinical characteristics and risk factors for disease severity in a large cohort of Turkish patients with PPP. METHODS: We conducted a cross-sectional, multicentre study of patients with PPP recruited from 21 tertiary centres across Turkey. RESULTS: In total, 263 patients (165 women, 98 men) were evaluated. Most patients (75.6%) were former or current smokers. The mean Palmoplantar Pustulosis Area and Severity Index (PPPASI) was 8.70 ± 8.06 and the mean Dermatology Life Quality Index (DLQI) score was 6.87 ± 6.08, and these scores were significantly correlated (r = 0.52, P < 0.001). Regression analysis showed that current smoking was significantly associated with increased PPPASI (P = 0.03). Coexisting psoriasis vulgaris (PsV) was reported by 70 (26.6%) patients. Male sex prevalence, PPP onset incidence, disease duration, DLQI, and prevalence of nail involvement and psoriatic arthritis (PsA) were significantly increased among patients with PPP with PsV. Of the 263 patients, 18 (6.8%) had paradoxical PPP induced by biologic therapy, and these patients had significantly increased mean DLQI and prevalence of PsA (r = 0.03, P = 0.001). CONCLUSION: Our data suggest that smoking is a risk factor for both PPP development and disease severity. Patients with PPP with PsV present distinct clinical features and patients with biologic therapy-induced paradoxical PPP have reduced quality of life and are more likely to have PsA.

A novel homozygous nonsense mutation in CAST associated with PLACK syndrome.

Peeling skin syndrome is a heterogeneous group of rare disorders. Peeling skin, leukonychia, acral punctate keratoses, cheilitis and knuckle pads (PLACK syndrome, OMIM616295) is a newly described form of PSS with an autosomal recessive mode of inheritance. We report a 5.5-year-old boy with features of PLACK syndrome. Additionally, he had mild cerebral atrophy and mild muscle involvements. Whole exome sequencing was performed in genomic DNA of this individual and subsequent analysis revealed a homozygous c.544G > T (p.Glu182*) nonsense mutation in the CAST gene encoding calpastatin. Sanger sequencing confirmed this variant and demonstrated that his affected aunt was also homozygous. Real-time qRT-PCR and immunoblot analysis showed reduced calpastatin expression in skin fibroblasts derived from both affected individuals compared to heterozygous family members. In vitro calpastatin activity assays also showed decreased activity in affected individuals. This study further supports a key role for calpastatin in the tight regulation of proteolytic pathways within the skin.

Relationship between the interleukin-6-174 gene and mannose-binding lectin codon 54 gene polymorphisms and condyloma acuminatum.

BACKGROUND: Several genes encoding different Th1 and Th2 cytokines may play crucial roles in host susceptibility to Condyloma acuminatum (CA). Mannose-binding lectin (MBL) is a serum lectin that mediates complement activation, and it is a member of innate immune system. MBL gene polymorphisms are considered to be associated with several infectious diseases. OBJECTIVE: In this study, we investigated the association between cytokines and MBL gene polymorphisms with CA. METHODS: Forty patients with CA and 40 healthy controls were enrolled in this study. These patients had not responded to at least a therapy modality and all patients had recurrent lesions. Polymorphism of cytokine [Th1 cytokines; tumour necrosis factor-α and interferon (IFN)-γ, Th2 cytokine; IL-6, T regulatory/suppressor cytokines; IL-10 and transforming growth factor-ß] genes studies were performed by Polymerase chain reaction sequence-specific primers method and MBL genotyping were studied by PCR-restriction fragment length polymorphism method. RESULTS: With the aid of agglomerative hierarchical cluster analysis, we categorized subjects into two main clusters (cluster 1; formed by the majority of patients with CA, cluster 2; formed by the majority of healthy controls), which were found to have significantly different distributions of IL-6 and MBL genotypes. Frequencies of IL-6 (-174) G/G (P < 0.001) and MBL AA (P < 0.001) polymorphisms were significantly greater in the cluster 1. In contrast, significantly lower frequencies of the IL-6 G/C (P = 0.046) genotype and MBL AB (P < 0.001) genotype were observed in cluster 1. CONCLUSION: These results suggest that the IL-6 G/G and MBL AA gene polymorphisms are potential risk factors and that the IL-6 G/C and MBL AB polymorphisms are a protective factor for occurrence and recurrence of CA.

The value of spectrophotometric intracutaneous analysis in the noninvasive diagnosis of nonmelanoma skin cancers.

BACKGROUND: Spectrophotometric intracutaneous analysis (SIAscopy) is a recently introduced, noninvasive, rapid and practical method for monitoring pigmented lesions, which calculates the amount of collagen, melanin and haemoglobin deep in the papillary dermis. AIM: To evaluate the value of SIAscopy in the diagnosis of nonmelanoma skin cancers (NMSC). METHODS: In total, 80 lesions of 76 patients were clinically evaluated by the first investigator, and the data recorded. Eight months after the clinical evaluation, all lesions were evaluated again by the same investigator, using images (SIAgraphs) obtained by the SIAscope. All SIAgraphs were also evaluated by a second investigator, and all dermatoscopic images by a third, independently of each other. All diagnoses were compared with histopathological diagnoses. RESULTS: The clinical diagnosis was calculated to have a sensitivity of 79% and specificity of 84%. The SIAscopic diagnoses of the first and second investigators had a sensitivity of 55% and 93%, and a specificity of 88% and 53%, respectively, while the dermatoscopic diagnoses of the third investigator had a sensitivity of 86% and specificity of 80%. There was no statistical accordance between the first and second investigators according to the accuracy of SIAscopic diagnoses (P < 0.01). The area under the curve for the receiver operator characteristic was 0.82 for clinical diagnosis, 0.73 and 0.80 for the SIAscopic evaluation of the first and the second investigators, respectively, and 0.87 for the dermatoscopic evaluation of the third investigator. CONCLUSIONS: Our findings show that dermatoscopic findings are more valuable than SIAscopic and clinical findings for the noninvasive diagnosis of NMSC. We consider that SIAscopy makes no substantial contribution towards the differential diagnosis of NMSC.

Toll-like receptor 9 polymorphism in patients with erythema multiforme, Stevens Johnson syndrome and Stevens Johnson syndrome/toxic epidermal necrolysis overlap syndrome.

BACKGROUND: "Toll like receptor" (TLR) 9 functions in stepping in of native immune system against different viral and bacterial pathogens and induction of adaptive immune response effectively. TLR 9 gene polymorphism makes host predisposed to microbial pathogens by affecting thefunctional capabilities of the receptor. OBJECTIVE: We aimed to determine if TLR 9 gene polymorphism makes a predisposition to "erythema multiforme" (EM), "Stevens Johnson syndrome" (SJS) and "Stevens Johnson syndrome/toxic epidermal necrolysis overlap syndrome" (SJS/TEN). METHODS: Forty-two patients clinically and/or histopathologically diagnosed as EM, SJS, and SJS/TEN overlap syndrome and 50 healthy control subjects were enrolled in our study. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method was applied for TLR 9 gene 1237 thymine/cytosine (T/C) polymorphism. Genotypes were determined according to bands occurring on agarose gel electrophoresis. RESULTS: In patients group, the frequencies of TT and TC genotypes were 73.8% and 26.2% while CC genotype wasn't detected. In control group, the frequencies of TT, TC and CC genotypes were 74%, 24%, and 2%. There wasn't a statistically significant difference for TT, TC and CC genotypes between patients and controls. The frequencies of T and C alleles were 84.5% and 15.5% in patients and 86% and 14% in controls, respectively. CONCLUSION: Our results showed that there isn't any association between TLR gene polymorphism and EM, SJS, SJS/TEN overlap syndrome (Tab. 1, Fig. 1, Ref. 30).

IL-1 cluster gene polymorphisms in Turkish patients with Behçet's disease.

Several cytokine genes may play crucial roles in host susceptibility to Behçet's Disease (BD), since the cytokine production capacity varies among individuals and depends on the cytokine gene polymorphisms. The association of the IL-1 cluster gene polymorphisms with the development of BD was investigated in this study. DNA samples were obtained from a Turkish population of 97 patients with BD, and 77 healthy control subjects. All genotyping (IL-1α, IL-1ß, IL-1R and IL-1Ra) experiments were performed using sequence specific primers PCR (PCR-SSP). When compared to the healthy controls, the frequencies of IL-1Ra IL-1α and IL-1R gene polymorphisms were not significantly different in BD patients. The frequency of IL-1ß-511 TT genotype was higher in the BD group in comparison to the control group. Interestingly, we demonstrated that IL-1 ß +3962 gene polymorphism seems to be associated with the presence of Erythema nodosum in BD patients. Our data suggest that polymorphisms in IL-1ß gene may affect host susceptibility to BD. In order to confirm the biological significance of our results, further studies should be performed in a large-scale study and/or in different ethnic groups.

Interleukin-4 gene polymorphisms confer Behçet's disease in Turkish population.

Several cytokine genes may play crucial roles in host susceptibility to Behçet's Disease (BD), because the cytokine production capacity varies among individuals and depends on the cytokine gene polymorphisms. The association of the IL-4 and IL-4Rα gene polymorphisms with the susceptibility to BD was investigated in this study. DNA samples were obtained from a Turkish population of 97 patients with BD and 76 healthy control subjects. All genotyping (IL-4 and IL-4Rα) experiments were performed using PCR sequence-specific primers. When compared with the healthy controls, the frequency of IL-4 -1098 TG and -590 CT genotypes was higher in the patients with BD. Analysis of allele frequencies showed that IL-4 -1098 G and IL-4 -590 T alleles were more common in the patients with BD when compared with healthy controls. Also, IL-4 TTC and haplotypes were found to confer BD. Interestingly, we demonstrated that IL-4Rα gene polymorphism seems to be associated with the Pathergy test positivity in patients with BD. Our data suggest that IL-4 gene promoter polymorphisms may affect susceptibility to BD and increase risk of developing the disease. However, in order to confirm and assess the association of IL-4 and IL-4Rα gene polymorphisms with the BD, large cohort studies are needed.

Investigation of ABCB1 gene polymorphism with colchicine response in Behçet's disease.

Colchicine is commonly used in the treatment of Behçet's disease. However, some patients are unresponsive to colchicine treatment. Adenosine triphosphate-binding cassette subfamily B member 1 (ABCB1) transports colchicine out of cells. We investigated a possible association of C3435T polymorphism of the ABCB1 (MDR1) gene with colchicine response in patients with Behçet's disease. We randomly selected 97 patients with Behçet's disease, examined ABCB1 (MDR1) gene C3435T polymorphisms, and evaluated patient responses to colchicine. Forty-three patients were colchicine responsive, while the remaining 54 patients were unresponsive. No significant difference was found between genotypic and allelic frequencies of the ABCB1 C3435T polymorphisms in patients with Behçet's disease and healthy volunteers. Also, there was no significant difference among responsive and nonresponsive patients. We concluded that ABCB1 C3435T polymorphism is not associated with a colchicine response in patients with Behçet's disease.

Cytokine gene polymorphisms in Behçet's disease and their association with clinical and laboratory findings.

The association of the cytokine gene polymorphisms with the development of Behçet's Disease (BD) was investigated in this study. DNA samples were obtained from a Turkish population of 97 unrelated patients with BD, and 127 unrelated healthy control subjects.All genotyping (IL-6, IL10, IFN-gamma, TGF-Beta1 and TNF-alpha) experiments were performed using sequence-specific primers PCR. The frequency of TGF-Beta1 codon 25 GG genotype was found significantly lower in BD patients compared to healthy control subjects. The IL-10 -1082 GA genotype was more frequent whereas the AA genotype was less common in the BD group compared to the control group. The association between clinial findings and cytokine gene polymorphisms was further investigated in the patients with BD. The frequency of IFN-gamma AA genotype was lower in the patients with genital ulcer. Additionally, it was found that the frequency of IL-6 -174 GG genotype was lower in the patients with Pathergy positivity. These results suggest that TGF-Beta1 and IL-10 gene polymorphisms may affect host susceptibility to BD. Also, to confirm the biological significance of our results, further studies should be performed on other population groups and in large number of cases.

Efficacy and safety of long-term mycophenolate sodium therapy in pemphigus vulgaris.

BACKGROUND: Pemphigus is a chronic immunobullous disease, characterized by formation of blisters and erosions in skin and/or mucous membranes. This severe disease requires systemic immunosuppressive therapy. However, some patients are refractory, and long-term use of immunosuppressive agents can cause serious side-effects. Mycophenolic acid is increasingly being used as a corticosteroid-sparing agent or as monotherapy in immunosuppressive regimens. OBJECTIVES: We aimed to evaluate the effectiveness of mycophenolate sodium, a sodium salt of mycophenolic acid, in the treatment of pemphigus vulgaris. METHODS: Six patients who were diagnosed as pemphigus vulgaris with active, refractory disease were treated with mycophenolate sodium. Three patients received mycophenolate sodium monotherapy; three patients received mycophenolate in combination with steroid. All patients were monitored regularly. RESULTS: Mycophenolate sodium was well tolerated with a similar efficacy of mycophenolate mofetil, and no side-effects have been observed. CONCLUSIONS: Mycophenolate sodium appears to be an effective and safe alternative in the treatment of pemphigus vulgaris.

Detection of parvovirus B19 DNA in the lesional skin of patients with Behçet's disease.

BACKGROUND: There is disagreement in the current evidence for viral aetiologies in the pathogenesis of Behçet's disease (BD). OBJECTIVES: To investigate the presence of B19 DNA in skin lesions of patients with BD, compare with the skin of healthy controls and evaluate its role in the pathogenesis. METHODS: In total, 40 patients diagnosed with BD according to the criteria proposed by the International Study Group for Behçet's Disease and routinely followed up at our centre were enrolled into the study. All the patients selected were in the active phase of disease. Skin and blood samples of patients with BD and of the healthy volunteers were examined for B19 serology, histopathology and genome expression. RESULTS: The quantity of B19 DNA in nonulcerative BD lesions of was significantly different from ulcerative lesions in the study group and from the skin of the healthy controls (P < 0.01). For the nonulcerative lesions, real-time PCR analysis for B19 DNA was found to be 64% sensitive (95% CI 42.5-82.0) and 85% specific (95% CI 62.1-96.6) with a cut-off value of > 154 IU/mL (P < 0.001). CONCLUSIONS: To the best of our knowledge, this is the first study that provides evidence for a possible causal link between BD and parvovirus B19, and our data suggest the presence of the virus, particularly in intact, nonulcerative skin lesions of BD. Limitations to this study include the limited number of participants, and the fact that the exact source of B19 DNA was undetected.

Comparison of short- and long-term cyclosporine A therapy in chronic idiopathic urticaria.

BACKGROUND: Chronic idiopathic urticaria is sometimes difficult to treat, with little response to antihistamine therapy. OBJECTIVE: In a limited number of severe chronic idiopathic urticaria patients, cyclosporine A (CsA) therapy was found to be effective. In this study, we compared the clinical efficacy and safety of short- and long-term CsA applications. METHODS: Twenty patients with severe disease, unresponsive to antihistamines and showing a positive autologous serum skin test (ASST) were randomized to 4 mg/kg per day of CsA for 4 or 12 weeks. The clinical efficacy was measured with a daily activity score of weal numbers and itch (UAS). The two groups were compared in terms of mean reduction in UAS and ASST response to pre-and post-treatment sera. RESULTS: The clinical improvement was dramatic in the first month of treatment in both groups. There was no significant difference in the frequency of responses, side effects and the reduction of UAS in either group. CONCLUSION: The preliminary results of our study suggest that CsA is clinically effective for chronic urticaria. The prolonged use of this therapy for more than 1 month provides little benefit in the clinical improvement.

Effects of long-term cyclosporine A therapy on renal functions in Behçet's disease.

Cyclosporin A (CsA), one of the most extensively investigated immunomodulatory agents, is widely used today in the treatment of various immunologically triggered dermatologic disorders. The immunologic basis for the therapeutic action of CsA depends on the suppression of lymphokine production by T cells. Due to its immunologic effects, this drug is also commonly preferred in Behcet's disease, especially with neurologic and ocular involvement. Since the course of this chronic disease presents remissions and exacerbations, drug therapy should be long term. Studies on the safety of long-term use of CsA in dermatologic diseases are limited. In this study, we aimed to evaluate the long-term use of CsA in Beh,et's disease without renal involvement. A total of 19 patients with ocular Beh,et's disease receiving CsA therapy for at least 1 year were included in this retrospective study. Changes in the parameters of renal function (creatinine clearance, creatinine level in serum), other adverse effects and their relation with cumulative CsA dosage were evaluated. The duration of CsA therapy and total dosage were not found to have a significant effect on the parameters of renal function, but, depending on clinical observations, the adverse effects seem to increase in the long term. We conclude that our results on renal function should be supported by renal biopsies.

Arterial lesions in Behçet's disease.

BACKGROUND: Arterial involvement is a rare but serious condition in the course of Behçet's disease. We aimed to assess the results of therapeutic approaches in our patients with arterial lesions caused by Behçet's disease. PATIENTS AND METHODS: The records of 534 patients with Behçet's disease between 1987 and 2002 were retrospectively evaluated for the presence of arterial lesions. All patients were followed up regularly at 3 to 6 months intervals. RESULTS: Arterial lesions were diagnosed in 21 (3.9%) patients. Eight of these patients had pulmonary artery aneurysms (PAA), and the other 13 patients had non-pulmonary arterial lesions. Urgent surgical intervention was performed in three patients with PAA leading to death in all three. In addition, three other patients died due to massive haemoptysis at home despite to immunosuppressive therapy. Only two out of eight patients with PAA are still alive who were treated with cyclophophamide and corticosteroids. Thirteen operations were performed in 7 out of 13 patients having non-pulmonary arterial lesions. Although ten of the operations were primary operations, three reoperations had to be performed. A stent-graft was applied for the management of an iliac artery aneurysm in one patient. Only one patient died 8 years after the first non-pulmonary arterial involvement following a type IV thoracoabdominal aortic aneurysm repair. Five patients with arterial occlusive lesions were successfully treated by corticosteroids. CONCLUSIONS: Pulmonary artery aneurysms in Behçet's disease patients have a poor prognosis despite any form of therapy. High dose corticosteroids alone can be successfully used for isolated non-pulmonary arterial occlusive lesions, unless disabling symptoms occur. Surgery or stent-graft insertion is indicated for non-pulmonary arterial aneurysms because these aneurysms entail high risk of complications.

Echocardiographic findings in subjects with psoriatic arthropathy.

BACKGROUND: Psoriatic arthropathy (PA) is a seronegative arthropathy with a 5-20% prevalence among psoriatics. In recent years, cardiovascular abnormalities have been shown in patients with seronegative arthropathies. OBJECTIVE/AIM: Since echocardiography is a non-invasive method to evidence cardiac abnormalities, we planned a study to evaluate heart involvement in subjects with psoriatic athropathy using this method. METHODS: A total of 21 subjects (15 women, six men) aged from 34 to 71 years were involved in this study. After PA diagnosis was confirmed by skeletal scintigraphic survey, patients were evaluated by Doppler echocardiogram for cardiovascular disturbances and the results were compared with those for a sex- and age-matched control group. RESULTS: The left ventricle end-diastolic and end-systolic diameters of the PA group were statistically different from those of the control group (P < 0.05), but no difference was observed in ejection fraction and the mitral E/A ratios. The presence of diastolic dysfunction was significantly related to the presence of arthropathy and the duration of psoriasis (P < 0.05). CONCLUSION: We conclude that mild diastolic dysfunction may accompany PA but our data should be confirmed by further studies.