Ustekinumab for the treatment of acrodermatitis continua of Hallopeau refractory to anti-TNF agents.

Acrodermatitis continua of Hallopeau (ACH) is a variant of pustular psoriasis that is often very difficult to treat. Almost all anti-psoriatic agents have been used in the treatment of ACH. Ustekinumab, a fully human monoclonal antibody of the IgG1 class, is directed to the shared p40 subunit of cytokines IL-12 and IL-23. Herein, we present our experience of ustekinumab use in a 50-year-old man who was resistant to anti-tumor necrosis factor-α agents. Though initial therapy with ustekinumab achieved a sustained response in our patient, after a seven months of interruption, retreatment resulted in a slower and poorer response than the initial regimen. Both responses of our patient reflects: (i) the recalcitrant chronic nature of ACH in some patients, (ii) the value of ustekinumab in ACH treatment, (iii) the fact that, as with other biologics, a loss of response may also occur with ustekinumab when the treatment is interrupted. All these data provides evidence for the fact that the course of ACH is unpredictable and possibly indicate that concerning current biologics used in the treatment of ACH, we have still failed to hit the target we aimed for.

Ultraviolet A1 Phototherapy in the Treatment of Early Mycosis Fungoides.

BACKGROUND: Phototherapy has been the mainstay of therapies for early mycosis fungoides (MF). The beneficial role of ultraviolet (UV) light on MF is suggested by the observation that lesions occur on non-sun-exposed areas. Therapeutic light sources that are available today are broadband UVB, psoralen and UVA, narrowband UVB, and long-wave UV (UVA1). Current literature provides increasing evidence on the use of UVA1 to treat MF. AIM: To investigate the treatment responses of early MF patients treated with fixed 30 J/cm2 doses of UVA1 phototherapy. MATERIAL AND METHODS: Nineteen patients with early MF, stage IA-IIA of the TNM staging system, received fixed 30 J/cm2 doses of UVA1, given 5 times weekly over 5 weeks. Therapeutic effectiveness was assessed by clinical examination and was confirmed by histological evaluation. RESULTS: Of the 19 patients, complete responses were achieved in 12 (63%) and partial responses were achieved in 7 (37%) patients after UVA1 radiation exposures. During the study, UVA1 therapy was well tolerated. During the follow-up, 7 (58%) of the 12 patients with complete response relapsed within 3 months of the UVA1 therapy. CONCLUSION: The current study provides clinical and histological evidence for the effectiveness of UVA1 (30 J/cm2 5 times a week for 5 weeks) as a skin-directed therapy in the treatment of early MF; however, such a treatment failed to maintain a long and sustained response. Thus, studies to identify the optimal dosing protocol regarding the therapeutic efficacy, the factors affecting relapse time/rate, and the necessity of maintenance treatment are needed.

Trichofolliculoma: a rare variant of hair follicle hamartoma.

Trichofolliculoma is a rare hair follicle hamartoma, which is often regarded as a hair follicle tumor. Mostly, it presents as a papule or nodule, involving the skin of the face and scalp area. A central, dilated keratin plugged ostium with vellus hair(s) is often present. We report a 19-year-old woman with typical clinical and histopathological findings of trichofolliculoma.

Treatment of Generalized Pustular Psoriasis of Pregnancy With Infliximab.

Generalized pustular psoriasis of pregnancy (GPPP) is a rare and severe condition that may impair the health of the mother and fetus. Effective treatment is essential, as treatment options for GPPP are limited due to concerns about unfavorable pregnancy outcomes. We report the case of a 22-year-old woman with GPPP that was unresponsive to systemic corticosteroids. We effectively treated the condition with infliximab at 30 weeks' gestation with an immediate clinical response and no detected serious adverse events except for an oral herpes infection in the patient and low birth weight in the neonate. Future studies are necessary to evaluate the safety and efficacy of infliximab treatment in GPPP.

Clinical characteristics of pediatric hidradenitis suppurativa: a cross-sectional multicenter study of 140 patients.

Hidradenitis suppurativa (HS) rarely affects pediatric patients. The literature on pediatric HS patients is scarce. This is a cross-sectional study based on case note review or interviews and clinical examination of 140 pediatric patients undergoing secondary or tertiary level care. Patients were predominantly female (75.5%, n = 105) with a median age of 16. 39% reported 1st-degree relative with HS. Median BMI percentile was 88, and 11% were smokers (n = 15). Median modified Sartorius score was 8.5. Notable comorbidities found were acne (32.8%, n = 45), hirsutism (19.3%, n = 27), and pilonidal cysts (16.4%, n = 23). Resorcinol (n = 27) and clindamycin (n = 25) were the most frequently used topical treatments. Patients were treated with tetracycline (n = 32), or oral clindamycin and rifampicin in combination (n = 29). Surgical excision was performed in 18 patients, deroofing in five and incision in seven patients. Obesity seemed to be prominent in the pediatric population and correlated to parent BMI, suggesting a potential for preventive measures for the family. Disease management appeared to be similar to that of adult HS, bearing in mind that the younger the patient, the milder the disease in majority of cases.

Transient reactive papulotranslucent acrokeratoderma in a 50-year-old woman: case report and review of the literature.

A 50-year-old woman who presented with intermittent symmetric edema and wrinkling of the palms after soaking in water was found to have transient reactive papulotranslucent acrokeratoderma (TRPA). This is the oldest patient ever reported to have this condition. The patient was advised to avoid water exposure as much as possible and to wear gloves. Topical treatment with 5% salicylic acid in Vaseline also provided some relief. TRPA presents with translucent, white, confluent papules that become evident on the palms after 3-5 minutes' exposure to water (the so-called 'hand-in-the-bucket' sign) and resolve within a short time after drying. It is a rare disorder with fewer than 40 cases having been reported in the world literature. The disease is seen mostly in female patients, with ages ranging from 6 to 44 years prior to our case in a 50-year-old woman. The most common histologic findings are hyperkeratosis and dilated eccrine ostia. The etiopathogenesis of the disease remains unknown but a transitory structural or functional alteration of components of the stratum corneum or aberration of the sweat duct have been considered. TRPA has been reported in patients with cystic fibrosis and more recently, in patients taking selective cyclo-oxygenase-2 inhibitors. Therefore, the pathogenesis of the condition appears to be related to increased water absorption as a result of an increased epidermal sodium level. Treatment with barrier creams such as hydrophilic petrolatum, glycerin emollients, 5-20% salicylic acid in Vaseline, 10% urea cream, and 12% ammonium lactate cream have been reported. Cases with associated hyperhidrosis respond well to aluminum chloride-containing products.

Treatment of idiopathic pyoderma gangrenosum with infliximab: induction dosing regimen or on-demand therapy?

Pyoderma gangrenosum is an ulcerative skin disease of unknown origin. Recently tumor necrosis factor alpha inhibitors have been gaining attention in the treatment of recalcitrant pyoderma gangrenosum. However, there is a lack of an optimal dosing strategy in the published literature about the treatment of idiopathic pyoderma gangrenosum, and this is responsible for substantially different treatment strategies. Therefore, it is necessary to report experiences in this patient population in order to develop an optimal dosing strategy and to clarify whether regularly scheduled or on-demand therapy is suitable for idiopathic pyoderma gangrenosum. Herein we report a recalcitrant case of an idiopathic pyoderma gangrenosum treated successfully with a dosing regimen similar to the one that has been used in psoriasis. By doing so, we were capable of controlling the disease and improving the quality of life in our patient.

Salivary epidermal growth factor levels in Behçet's disease and recurrent aphthous stomatitis.

BACKGROUND: Epidermal growth factor (EGF) in saliva is cytoprotective against injuries and contributes to the maintenance of the integrity of the gastrointestinal mucosa. Low salivary EGF levels have been observed in patients with various forms of oral mucosal disease. OBJECTIVE: Our aim was to determine whether salivary EGF is low in patients with recurrent aphthous stomatitis (RAS) or those with Behçet's disease (BD) when compared with healthy controls. METHODS: The study population consisted of 33 BD and 16 RAS patients and 60 healthy controls. Measurement of EGF concentration in human saliva was performed with an enzyme-linked immunosorbent assay using an antibody-coated solid phase. RESULTS: The mean salivary EGF levels (+/-SD) of active (with oral ulceration) and inactive stages (absence of oral ulceration) of BD (1,939.7 +/- 1,561.5 and 2,305.7 +/- 1,481.6 pg/ml, respectively) and RAS patients (1,650.5 +/- 704.7 and 1,069.9 +/- 539.2 pg/ml, respectively) were both lower than those of the healthy controls (2,758.7 +/- 1,657.9 pg/ml) (p < 0.05 for each). CONCLUSIONS: BD and RAS patients have reduced salivary EGF levels even in the absence of oral ulcerations. EGF could be involved in the pathogenesis of BD and RAS by disturbing the mucosal integrity that may result in a susceptibility to the development of oral ulcers in these diseases.

The assessment of cardiac functions by tissue Doppler-derived myocardial performance index in patients with Behcet's disease.

Vascular involvement is one of the major characteristics of Behcet's disease (BD). However, there are controversial findings regarding cardiac involvement in BD. Although early reports demonstrated that there is diastolic dysfunction in BD, conflicting results were found in the following trials. Hence, a new method for more objectively estimating the cardiac functions is needed. For this aim, we used high-usefulness tissue Doppler echocardiography for detailed analysis of cardiac changes in BD patients because this method was superior to other conventional echocardiographic techniques. The study population included 42 patients with BD (19 men, 23 women; mean age, 35 +/- 10 years, mean disease duration, 2.7 +/- 1.6 years) and 30 healthy subjects (14 men, 16 women; mean age, 38 +/- 7 years). Cardiac functions were determined using echocardiography, comprising standard two-dimensional and conventional Doppler and tissue Doppler imaging (TDI). Peak systolic myocardial velocity at mitral annulus, early diastolic mitral annular velocity (Em), late diastolic mitral annular velocity (Am), Em/Am, and myocardial performance index (MPI) were calculated by TDI. The conventional echocardiographic parameters and tissue Doppler measurements were similar between the groups. Tissue Doppler derived mitral relaxation time was longer (75 +/- 13 vs 63 +/- 16 msn, p = 0.021) in patients with BD. There was statistically significant difference between the two groups regarding left ventricular MPI (0.458 +/- 0.072 vs 0.416 +/- 0.068%, p = 0.016), which were calculated from tissue Doppler systolic time intervals. There was also significant correlation between the disease duration and MPI (r = 0.38, p = 0.017). We have demonstrated that tissue Doppler-derived myocardial left ventricular relaxation time and MPI were impaired in BD patients, although systolic and diastolic function parameters were comparable in the patients and controls.

Topical tetracycline in the treatment of acne vulgaris.

BACKGROUND: Topical tetracycline was the first topical antibiotic approved for the treatment of acne, its use has been limited because of the skin penetration problems of the active ingredient. OBJECTIVES: The objective of this study was to evaluate the effectiveness of a new formulation of topical tetracycline [Imex, tetracycline hydrochloride 3%, 20g] monotherapy in the treatment of mild to moderate acne vulgaris. METHODS: The sample group consisted of 87 volunteer students of both sexes with grade 1 to grade 2 acne as assessed by Investigator's Global Assessment (IGA) severity grading system. Subjects were instructed to apply topical tetracycline twice daily for 8 weeks. Subject were evaluated at baseline and at weeks 2, 4, and 8. RESULTS: Of 87 subjects, 68 completed the 8-week treatment period. The mean reduction rates of opened comedones were 55.4%, closed comedones were 27.1%, papules were 24.8%, pustules were 27.3%. After 8 weeks of treatment, a statistically significant reduction was only observed in the mean counts of the papules and pustules (P < 0.001). CONCLUSION: Tetracycline is a well-tolerated topical agent and is particularly effective in the treatment of inflammatory lesions in acne.

Prevalence of smoking, alcohol consumption and metabolic syndrome in patients with psoriasis.

BACKGROUND: Coexistence of obesity, hypertension, insulin resistance and dyslipidemia is defined as metabolic syndrome (MBS), which is among the important risk indicators for cardiovascular diseases, diabetes and stroke. Smoking and alcohol consumption are the other factors which lead to an increase in the risk of cardiovascular disease. OBJECTIVE: To investigate the prevalence of metabolic syndrome, smoking and alcohol consumption in psoriasis patients and the relationship between disease severity and these factors. METHODS: This cross-sectional study enrolled 563 patients with chronic plaque-type psoriasis, all of which completed a questionnaire and underwent a complete physical examination. Data about MBS components, psoriasis severity/duration, smoking and alcohol consumption, and cardiovascular diseases were recorded. RESULTS: A total of 563 patients with ages ranging from 18 to 78 years were evaluated. Metabolic syndrome was found in 12.6% of the patients [central obesity (38.7%), hypertension (14.3%), dyslipidemia (18.6%), diabetes (9.2%)], while 50.3% had smoking, and 3.3% had alcohol consumption. Patients with metabolic syndrome were older and more likely to have a longer disease duration than those without metabolic syndrome (p<0.05 for each). The prevalence of metabolic syndrome was higher in women than in men. Psoriasis was more severe in patients with central obesity, diabetes and smoking than in those without (p<0.05 for each). STUDY LIMITATIONS: Retrospective design. CONCLUSIONS: Our results indicate that MBS is a risk factor for psoriasis patients with advanced age. The relationship between disease severity and obesity, diabetes, and smoking in psoriasis patients indicates that the patients should be informed about the potential metabolic risks and receive therapies for behavioral changes besides anti-psoriatic treatment in order to minimize these risks.

A mild form of Proteus syndrome.

Proteus syndrome is a multisystem disorder and diagnosis has been difficult because of the variability of the syndrome's manifestations. Dermatologists have an important role as cutaneous findings could provide clues for the early diagnosis of the disease. Herein we report a case who had cerebriform connective tissue nevus and lipoma as the sole manifestations of the disease.

Early onset linear focal elastosis in a Turkish boy.

A 14-year-old boy applied to our outpatient clinic with a three-month history of lesions on the back. The physical examination revealed linear, yellow, stria-like palpable bands surrounded by a slight erythema extending horizontally across the back. Histopathological examination of the lesional skin demonstrated coarseness in collagen bundles and homogenization and decrement in elastic fibers with van Gieson stain. These features were consistent with linear focal elastosis. In the literature, linear focal elastosis is mainly reported in the elderly. We describe here a case of early linear focal elastosis arising in a 14-year-old Turkish boy.

Caspase 9 is decreased in psoriatic epidermis.

Psoriasis is a proliferative and inflammatory disease of the skin. Caspase 9 is responsible for initiating the caspase activation cascade during apoptosis. Apoptosis is a physiological mechanism of homeostasis and development, and caspases are the executioners of apoptosis. This study reports the immunohistochemical localisation of caspase 9 in psoriatic skin and compares it with that seen in normal, healthy control skin. Skin biopsy specimens of lesions were obtained from 15 patients with plaque type psoriasis vulgaris. The specimens were labelled immunohistochemically for binding of an anti-caspase 9 primary antibody. Biopsies of healthy skin from 10 age-matched and sex-matched healthy control individuals were also analysed. The caspase 9 positive cell fraction was calculated for both epidermal and dermal cells in psoriatic lesions and healthy control skin. Counts of caspase 9 positive cells from the epidermis of psoriatic skin lesions were significantly lower than those seen in healthy skin (p<0.05). The caspase 9 immunolabelled perivascular cell counts in the dermis were not statistically significantly different in psoriatic lesions versus normal skin (p>0.05). Psoriatic epidermis contains little of the apoptotic marker, caspase 9. The results of this study are indicative of decreased apoptosis in psoriatic epidermis, and no change in the perivascular area in psoriatic lesions. These findings support the idea that decreased apoptosis is seen in psoriatic epidermal cells. Greater understanding of the nature of the disease may open new avenues for further therapeutic modalities.

Pyoderma Gangrenosum: A Report of 27 Patients.

The aim of this study was to document the profile of pyoderma gangrenosum (PG) patients who were treated in our clinic and to compare our patients' clinical and demographic characteristics with those described in the literature to help our understanding of the total burden of PG. A total of 27 (17 women, 10 men) patients with a mean age 48.6 years at diagnosis were included in the study. Seven (25.9%) of them had 3 or more ulcers. The lower extremity was the most common site of occurrence (92.5%). During the study period, 6 patients were admitted twice, and 7 were admitted 3 or more times (range 1 to >10), and the median length of stay was 27 days. A concomitant disease was present in PG patients especially in those between 20 and 40 years of age. Systemic therapy was used in 21 (91.3%) patients, 17 patients were treated with systemic corticosteroids, either alone in 7 patients or combination with other agents in 10 patients. Three of our patients died because of disease or treatment-related complications during the study period. Despite the high (70.3%) percentage of the PG patients with improving disease at the time of discharge, 1 year after hospital discharge, one third of our 27 patients still had PG requiring readmission. In conclusion, none of the current therapies provide satisfying results in all of the patients, and our data indicate a long-standing unmet need for effective therapy for the unexpected course of PG.

A Rare Cause of Lower Extremity Ulcers: Prolidase Deficiency.

Prolidase deficiency is an autosomal recessive disorder, which is associated with chronic skin ulcers, a characteristic facial appearance, mental retardation, and recurrent infections. This study describes 4 patients with recurrent leg ulcerations and abnormal facies who were first clinically suspected of prolidase deficiency and then biochemically confirmed. Two siblings and 2 other patients were admitted to our clinic at different times, and they had some common features such as chronic leg and foot ulcers recalcitrant to treatment, consanguineous parents, facial dysmorphism, mental retardation, and widespread telangiectasias. Physical examination and detection of low prolidase level in blood finally led us to the diagnose of ulcers secondary to prolidase deficiency. Prolidase deficiency is a rare genodermatosis and must be considered in the differential diagnosis of recurrent leg and foot ulcers that develop at an early age.

TUR-PSO: A cross-sectional, study investigating quality of life and treatment status of psoriasis patients in Turkey.

Psoriasis is a common inflammatory disease that has a severe impact on quality of life. There is lack of data regarding epidemiological and clinical features of psoriasis patients in Turkey, a country with a population of 76 million. The aim of this study was to define the demographic and clinical characteristics, quality of life and treatment patterns of psoriasis patients in Turkey. A cross-sectional observational study was conducted at 40 centers, chosen from geographically diverse locations in Turkey. Patients diagnosed with psoriasis were assessed by investigators who were specialists of dermatology using standardized study questionnaire forms. Dermatology Life Quality Index (DLQI) and EuroQol-5 dimension (EQ-5D) forms were also filled out by each patient. 3971 psoriasis patients were included in this study. 24.2% of plaque psoriasis patients had moderate to severe psoriasis (Psoriasis Area and Severity Index, ≥10). Mean DLQI was 7.03 ± 6.02; quality of life was moderately, severely or very severely affected in 49.2% of patients. The most severely affected component of EQ-5D was anxiety/depression. Among all patients, 22.9% were not receiving any treatment, 39.8% were receiving only topical treatment, 11.5% were on phototherapy, 26.1%, were taking conventional systemic agents and 4.1% were on a biologic treatment. 31.3% of psoriasis patients with moderate to severe disease were treated with only topical agents and only 30.5% of moderate to severe psoriasis patients were receiving systemic therapy. Moderate to severe psoriasis has a considerable impact on quality of life. Treatment in Turkey of patients with moderate to severe psoriasis is insufficient.

Lack of prolidase causes a bone phenotype both in human and in mouse.

The degradation of the main fibrillar collagens, collagens I and II, is a crucial process for skeletal development. The most abundant dipeptides generated from the catabolism of collagens contain proline and hydroxyproline. In humans, prolidase is the only enzyme able to hydrolyze dipeptides containing these amino acids at their C-terminal end, thus being a key player in collagen synthesis and turnover. Mutations in the prolidase gene cause prolidase deficiency (PD), a rare recessive disorder. Here we describe 12 PD patients, 9 of whom were molecularly characterized in this study. Following a retrospective analysis of all of them a skeletal phenotype associated with short stature, hypertelorism, nose abnormalities, microcephaly, osteopenia and genu valgum, independent of both the type of mutation and the presence of the mutant protein was identified. In order to understand the molecular basis of the bone phenotype associated with PD, we analyzed a recently identified mouse model for the disease, the dark-like (dal) mutant. The dal/dal mice showed a short snout, they were smaller than controls, their femurs were significantly shorter and pQCT and µCT analyses of long bones revealed compromised bone properties at the cortical and at the trabecular level in both male and female animals. The differences were more pronounce at 1 month being the most parameters normalized by 2 months of age. A delay in the formation of the second ossification center was evident at postnatal day 10. Our work reveals that reduced bone growth was due to impaired chondrocyte proliferation and increased apoptosis rate in the proliferative zone associated with reduced hyperthrophic zone height. These data suggest that lack of prolidase, a cytosolic enzyme involved in the final stage of protein catabolism, is required for normal skeletogenesis especially at early age when the requirement for collagen synthesis and degradation is the highest.

Prevalence of smoking, alcohol consumption and metabolic syndrome in patients with psoriasis

Abstract: Background: Coexistence of obesity, hypertension, insulin resistance and dyslipidemia is defined as metabolic syndrome (MBS), which is among the important risk indicators for cardiovascular diseases, diabetes and stroke. Smoking and alcohol consumption are the other factors which lead to an increase in the risk of cardiovascular disease. Objective: To investigate the prevalence of metabolic syndrome, smoking and alcohol consumption in psoriasis patients and the relationship between disease severity and these factors. Methods: This cross-sectional study enrolled 563 patients with chronic plaque-type psoriasis, all of which completed a questionnaire and underwent a complete physical examination. Data about MBS components, psoriasis severity/duration, smoking and alcohol consumption, and cardiovascular diseases were recorded. Results: A total of 563 patients with ages ranging from 18 to 78 years were evaluated. Metabolic syndrome was found in 12.6% of the patients [central obesity (38.7%), hypertension (14.3%), dyslipidemia (18.6%), diabetes (9.2%)], while 50.3% had smoking, and 3.3% had alcohol consumption. Patients with metabolic syndrome were older and more likely to have a longer disease duration than those without metabolic syndrome (p<0.05 for each). The prevalence of metabolic syndrome was higher in women than in men. Psoriasis was more severe in patients with central obesity, diabetes and smoking than in those without (p<0.05 for each). Study Limitations: Retrospective design. Conclusions: Our results indicate that MBS is a risk factor for psoriasis patients with advanced age. The relationship between disease severity and obesity, diabetes, and smoking in psoriasis patients indicates that the patients should be informed about the potential metabolic risks and receive therapies for behavioral changes besides anti-psoriatic treatment in order to minimize these risks.