The Combined Application of Bleomycin and Triamcinolone for Treating Refractory Keloids.

BACKGROUND: Triamcinolone acetate injections are considered the first treatment option for keloids, but quite high proportions of keloids either do not respond to triamcinolone or develop recurrence. Beneficial effects of intralesional bleomycin have been recently shown in the treatment of keloids and hypertrophic scars. However, the efficacy of combination therapy using intralesional triamcinolone and bleomycin remains undetermined. OBJECTIVE: The purpose of this study was to evaluate the efficacy of using bleomycin and triamcinolone mixture to treat refractory keloids. MATERIALS AND METHODS: In total, 33 patients with resistant keloids (including 8 men and 25 women) and a mean age of 36.52 years (age range of 18-65 years) were enrolled in this study. A mixture of bleomycin (1 u/cc) with triamcinolone acetonide (13.3 mg/cc) was injected intralesionally into the keloids every 4 to 6 weeks for a maximum of 6 cycles. The clinical improvement was evaluated using the Japan Scar Scale (JSS) and the physician's global assessment of the flattening of the lesions. Side effects were also noted and recorded. RESULTS: In all patients, the total JSS scores decreased significantly after treatment (2.33 ± 1.05), compared with baseline (11.61 ± 2.59), ( p < .001); 26 keloids (78.8%) showed an excellent response (75%-100% flattening), 7 keloids (21.2%) showed a fair response (25%-75% flattening), and 0 keloids (0%) showed a poor response (<25% flattening). Observed side effects were ulceration (33.3%), hyperpigmentation (33.3%), hypopigmentation (15.15%), secondary infection (33.3%), and telangiectasis (15.15%). CONCLUSION: The combined use of bleomycin and triamcinolone offers a promising treatment option for individuals who have not responded well to traditional therapies.

Brain MRI findings in patients with bullous pemphigoid: A case-control study.

Evidence suggests that bullous pemphigoid (BP) is associated with multiple neurological disorders. We aimed to compare brain magnetic resonance (MRI) findings between BP patients and a control group. This case-control study included patients with BP referred to two dermatology clinics during a two-year period. A group of individuals attending the same clinics for cosmetic procedures were selected as controls. First, participants' general information including age, gender, education, weight and underlying disease was recorded. For BP patients, the drugs and the BP Disease Area Index (BPDAI) were recorded as well. Then, all participants underwent brain MRI without contrast. The Fazekas scale, the general cerebral atrophy (GCA) score, and the Medial Temporal lobe Atrophy (MTA) score were used to assess MRI images. Overall, 24 BP patients and 24 controls were evaluated in this study. Both groups were comparable regarding age, gender and education. However, diabetes and hypertension were more frequent in the control group. The mean BPDAI total score was 51.39 ± 68.92 in BP patients and most of them used rituximab (41.7%). None of the participants had MS or Alzheimer MRI patterns. There was no difference between groups in terms of GCA and MTA scores. Furthermore, the frequency of partially empty sella did not differ significantly between BP patients and controls (p = 0.461); nevertheless, grade-3 Fazekas was significantly higher in BP patients compared to controls (25% vs. 0%, p = 0.019). Of note, one BP patient had an epidermoid cyst and another had moderate enlargement of three ventricles. Also, new infarcts were observed in two and old infarcts in four BP patients. Although the majority of abnormal brain MRI findings were more frequent in BP patients compared to controls, only grade-3 Fazekas was significantly higher and acute infarcts were exclusively observed in BP patients.

Mutation update: The spectra of PLEC sequence variants and related plectinopathies.

Plectin, encoded by PLEC, is a cytoskeletal linker of intermediate filaments expressed in many cell types. Plectin consists of three main domains that determine its functionality: the N-terminal domain, the Rod domain, and the C-terminal domain. Molecular defects of PLEC correlating with the functional aspects lead to a group of rare heritable disorders, plectinopathies. These multisystem disorders include an autosomal dominant form of epidermolysis bullosa simplex (EBS-Ogna), limb-girdle muscular dystrophy (LGMD), aplasia cutis congenita (ACC), and an autosomal recessive form of EBS, which may associate with muscular dystrophy (EBS-MD), pyloric atresia (EBS-PA), and/or congenital myasthenic syndrome (EBS-MyS). In this study, genotyping of over 600 Iranian patients with epidermolysis bullosa by next-generation sequencing identified 15 patients with disease-causing PLEC variants. This mutation update analyzes the clinical spectrum of PLEC in our cohort and in the literature and demonstrates the relationship between PLEC genotype and phenotypic manifestations. This study has integrated our seven novel PLEC variants and phenotypic findings with previously published data totaling 116 variants to provide the most complete overview of pathogenic PLEC variants and related disorders.

Intralesional bleomycin versus intralesional triamcinolone in the treatment of keloids and hypertrophic scars.

Bleomycin is a known chemotherapeutic agent whose beneficial effects have been recently shown in the treatment of keloids and hypertrophic scars, however, it is unclear how effective it is in comparison with corticosteroids. We aimed to compare the safety and efficacy of intralesional bleomycin versus intralesional triamcinolone in the treatment of hypertrophic scars and keloids. Sixty patients were divided into two groups and treated by intralesional injection of triamcinolone (20 mg/ml) or bleomycin (1.5 mg/ml). The treatments were repeated every 3 weeks until the lesions flattened or for a maximum of six sessions. The clinical improvement was evaluated using the Japan scar workshop (JSW) scar scale (JSS) and the physician global assessment of flattening of the lesions. Side effects were also noted and recorded. 55 patients completed the study, 4 patients from the bleomycin group and 1 patient from the triamcinolone group dropped out of the study. In both groups, the total JSS scores decreased significantly after treatment compared to baseline (p < 0.001); however, the difference between groups was not statistically significant after treatment (p = 0.052). Moreover, the degree of flattening of the lesions was comparable between groups (p = 0.933). Side effects in the triamcinolone group were Hypopigmentation(55.2%), atrophy(51.7%), and telangiectasia(41.4%) and in bleomycin group included persistent pain after injection (61.5%), ulceration (69.2%), hyperpigmentation(76.9%), and secondary infection (34.6%). Intralesional bleomycin (1.5 mg/ml) is effective as triamcinolone(20 mg/ml) in the treatment of keloids and hypertrophic scars, however, bleomycin should be used carefully, due to adverse events such as pain, ulceration, and hyperpigmentation.

Efficacy of oral tofacitinib in refractory chronic spontaneous urticaria and urticarial vasculitis.

The treatment of chronic urticaria (CU) is difficult, currently, antihistamines (AH) are the mainstay of treatment, however, up to 40% of patients do not respond to even high (four-fold) daily doses of AH. Tofacitinib is, a small-molecule that blocks JAK1/3 and inhibits intracellular signaling of multiple key cytokines involved in the inflammatory cascade and its beneficial effects were reported in patients with mast cell activation disease but there is no report in patients with urticaria. Here, we present four cases of refractory CU and one case of urticarial vasculitis (UV) that were managed with tofacitinib. Despite the long-term unresponsiveness of various treatments in our patients, the addition of tofacitinib significantly improved the urticarial activity and ultimately led to tapering and discontinuation of cyclosporine or AH. In conclusion, tofacitinib appears to downregulate inflammatory phenomena associated with mast cells and might be a new therapeutic option for patients with refractory CU or UV.

A review of reported infectious events following rituximab therapy in pemphigus patients.

Pemphigus is a rare autoimmune blistering condition that used to be fatal before the introduction of corticosteroid (CS) and immunosuppressive agents. Rituximab is a monoclonal anti-CD-20 antibody that induces the pathologic B-cells apoptosis with significant efficacy in the treatment of pemphigus. The application of rituximab can lead to infectious events. We aim to review the reported infectious events in pemphigus patients who previously received rituximab and classify them based on the causative agents. A thorough search of PubMed was conducted using the keywords "rituximab," "pemphigus," "infection," "viral disease," "viral infection," "complication," "efficacy" and their combinations also applying their equivalent Mesh terms and including the references cited in each study. All studies that mentioned at least one infectious event were included. A total of 77 infectious events in 68 patients were reported in the literature out of which the most reported causative agent was viral but the most fatal one found to be bacterial. Although rituximab therapy has shown promising results in controlling pemphigus patients mainly the refractory cases, given possible fatal outcomes, we believe the medical profile of the patients before initiating the therapy warrants careful examination to search for any risk factors or predisposing conditions.

Whole-Transcriptome Analysis by RNA Sequencing for Genetic Diagnosis of Mendelian Skin Disorders in the Context of Consanguinity.

BACKGROUND: Among the approximately 8000 Mendelian disorders, >1000 have cutaneous manifestations. In many of these conditions, the underlying mutated genes have been identified by DNA-based techniques which, however, can overlook certain types of mutations, such as exonic-synonymous and deep-intronic sequence variants. Whole-transcriptome sequencing by RNA sequencing (RNA-seq) can identify such mutations and provide information about their consequences. METHODS: We analyzed the whole transcriptome of 40 families with different types of Mendelian skin disorders with extensive genetic heterogeneity. The RNA-seq data were examined for variant detection and prioritization, pathogenicity confirmation, RNA expression profiling, and genome-wide homozygosity mapping in the case of consanguineous families. Among the families examined, RNA-seq was able to provide information complementary to DNA-based analyses for exonic and intronic sequence variants with aberrant splicing. In addition, we tested the possibility of using RNA-seq as the first-tier strategy for unbiased genome-wide mutation screening without information from DNA analysis. RESULTS: We found pathogenic mutations in 35 families (88%) with RNA-seq in combination with other next-generation sequencing methods, and we successfully prioritized variants and found the culprit genes. In addition, as a novel concept, we propose a pipeline that increases the yield of variant calling from RNA-seq by concurrent use of genome and transcriptome references in parallel. CONCLUSIONS: Our results suggest that "clinical RNA-seq" could serve as a primary approach for mutation detection in inherited diseases, particularly in consanguineous families, provided that tissues and cells expressing the relevant genes are available for analysis.

Metabolomic signature of amino acids in plasma of patients with non-segmental Vitiligo.

INTRODUCTION: Vitiligo pathogenesis is complicated, and several possibilities were suggested. However, it is well-known that the metabolism of pigments plays a significant role in the pathogenicity of the disease. OBJECTIVES: We explored the role of amino acids in vitiligo using targeted metabolomics. METHODS: The amino acid profile was studied in plasma using liquid chromatography. First, 22 amino acids were derivatized and precisely determined. Next, the concentrations of the amino acids and the molar ratios were calculated in 31 patients and 34 healthy individuals. RESULTS: The differential concentrations of amino acids were analyzed and eight amino acids, i.e., cysteine, arginine, lysine, ornithine, proline, glutamic acid, histidine, and glycine were observed differentially. The ratios of cysteine, glutamic acid, and proline increased significantly in Vitiligo patients, whereas arginine, lysine, ornithine, glycine, and histidine decreased significantly compared to healthy individuals. Considering the percentage of skin area, we also showed that glutamic acid significantly has a higher amount in patients with less than 25% involvement compared to others. Finally, cysteine and lysine are considered promising candidates for diagnosing and developing the disorder with high accuracy (0.96). CONCLUSION: The findings are consistent with the previously illustrated mechanism of Vitiligo, such as production deficiency in melanin and an increase in immune activity and oxidative stress. Furthermore, new evidence was provided by using amino acids profile toward the pathogenicity of the disorder.

Cytomegalovirus-induced cutaneous ulcer mimicking vasculitis in a patient with systemic lupus erythematous: A case report and review of the literature.

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease which can be complicated with cytomegalovirus (CMV) infection during its course. CMV reactivation can mimic an SLE flare and lead to delay in diagnosis. Here, we reported a previously diagnosed SLE patient who presented with fever, leukopenia, and cutaneous ulcers. Initially, this was diagnosed as an SLE flare and the patient was treated with higher doses of corticosteroids but no improvement was observed. Both nuclear and cytoplasmic inclusions inside the endothelial cells in the skin biopsy as well as positive immunohistochemistry (IHC) staining for CMV antigen were clues to the correct diagnosis of CMV reactivation. Treatment with ganciclovir resulted in clinical resolution. In this report, a very rare clinical form of CMV infection manifesting as cutaneous necrotizing vasculitis on the lower extremity is described and the literature regarding this case is reviewed.

Ingenol Mebutate Gel 0.05% in the Treatment of Anogenital Warts: A Prospective Controlled Trial Comparing It With Topical Podophyllin Solution 25.

BACKGROUND: Anogenital warts (AGWs) are a common therapeutic challenge. All therapies are associated with burning, pain, and frustrating high rate of recurrence. The search for a new alternative continues. Recently, a diterpene ester extracted from the Euphorbia peplus plant (ingenol mebutate [IM]) has been shown to possess activity against AGWs. OBJECTIVE: This study aimed to compare and evaluate the therapeutic efficacy and safety of topical 0.05% ingenol gel with another herbal extract medication (topical 25% podophyllin solution) in treatment of AGWs. METHODS: This was a comparative single blinded nonrandomized, 2-arm trial of ingenol 0.05% gel versus podophyllin solution 25% administered up to 6 times to patients with AGWs. To evaluate the therapeutic efficacy, the complete clearance rate and recurrence rate were assessed 1 and 12 weeks after last treatment, respectively. Safety was assessed by occurrence and severity of pain and local skin reaction (LSR). RESULTS: Of 31 and 36 patients in the IM group and podophyllin group who completed the study, initial complete resolution was observed in 20 (64.5%) and 14 (38.9%) patients, respectively (P = 0.03). The initial clearance was faster in the IM group (2.00 ± 0.91 weeks) compared with the podophyllin group (4.21 ± 1.05 weeks, P = 0.00). After 3 months, recurrence was seen in 13 (65.0%) of 20 patients in the IM group and 6 (42.8%) of 14 in the podophyllin group (P = 0.20). The number of patients with complete resolution after 3 months was not different between the 2 groups (7/31 in the IM group and 8/36 in the podophyllin group, P = 0.97). The mean ± SD severity scores for LSR and pain in the IM group were 6.65 ± 1.76 and 6.13 ± 2.57, respectively, which was significantly higher than their scores (3.39 ± 1.57 and 2.58 ± 1.38) in the podophyllin group (P = 0.00). CONCLUSION: Ingenol mebutate 0.05% gel is effective as podophyllin 25% solution in treating AGWs, with further benefit of being much more rapid. However, high recurrence rate, sever pain, and LSR limit its use.

Evaluation of serum level of sex hormones in women with frontal fibrosing alopecia in comparison to healthy controls.

The pathogenesis of frontal fibrosing alopecia (FFA) is still unknown while hormonal factors have been postulated to play a role. There is scarce evidence with divergent results on the role of sex hormones in FFA. To evaluate the possible association between sex hormone levels and FFA, this study included 30 female cases of FFA and 34 healthy controls. Serum free testosterone, dehydroepiandrosterone sulfate (DHEAS), Luteinizing hormone (LH), follicle-stimulating hormone (FSH), 17-OH progesterone, androstenedione, and prolactin levels were measured in all subjects. Median and interquartile ranges of DHEAS and androstenedione were 79.26 (52.91-195.50) and 1.41 (0.90-2.29) in patients and 152.34 (81.72-218.63) and 2.31 (1.54-2.84) in healthy controls, respectively. The serum levels of DHEAS and androstenedione were significantly lower in FFA patients in comparison with healthy controls (P-value = .038 and .012, respectively). There were no significant differences in serum levels of free testosterone, LH, FSH, 17-OH progesterone, and prolactin between the FFA group and the control group The lower serum levels of DHEAS and androstenedione in FFA patients compared to controls is supporting a new growing concept of the low androgen level theory in the pathogenesis FFA, while the exact mechanism, clinical significance, and also the potential therapeutic effects of these hormones in FFA remain to be determined in future studies.

Ingenol mebutate for the management of cryotherapy-resistant anogenital warts.

Ingenol mebutate (IM), as an active compound, is derived from the sap of the Euphorbia peplus, which is an FDA-approved plant for the treatment of actinic keratosis. Some reports have demonstrated that the IM gel 0.05% is safe and effective in the treatment of external anogenital warts (AGWs) but the efficacy of the drug on the recalcitrant AGWs is not clear. This article assesses the efficacy and safety of the IM gel 0.05% for cryotherapy -resistant AGWs. Totally, 15 cryotherapy-resistant patients with AGWs (including 8 men and 7 women) and a mean age of 34 years old (age range of 23-50 years old) were enrolled in this study. IM gel 0.05% was applied carefully on the AGWs every two weeks for a maximum of three cycles. The complete clearance rate and recurrence rate were assessed 1 week and 3 months after the last treatment, respectively. Safety was assessed by the occurrence of local skin reaction and the severity of pain was evaluated using the 10-point Visual Analogue Scale. Initially, the AGWs were cleared completely in 10 (66%) patients while 4 (40%) and all of (100%) the patients experienced a recurrence in the 3- and 12-months follow-ups, respectively. All the 15 patients experienced some degrees of pain and local adverse reactions. The mean score of the reported pain was equal to 5.87 ± 2.39. The use of IM gel 0.05% in the treatment of the difficult-to-treat cases of AGWs is associated with a high recurrence rate despite the initial rapid and effective clearance of the lesions. Also, the high level of local adverse reactions and severe pain are other prohibitive factors in the treatment of recalcitrant AGWs with the IM.

Lepromatous leprosy presenting with type II reaction before and type I reaction after treatment.

Lepromatous leprosy is associated with a high bacillary load and poor cellular immune response. Early dermatologic manifestations include erythematous macules, papules, nodules, and plaques with a symmetrical distribution. Leprosy also shows two major reaction states including type I (reversal reaction) and type II (vasculitis). These reactions are usually seen in some patients who are undergoing treatment. Herein, we report an interesting patient with lepromatous leprosy who presented with skin lesions of type II reaction without receiving any anti-leprosy treatment and surprisingly showed a type I reaction eight months after the beginning of the treatment.

Genome-wide single nucleotide polymorphism-based autozygosity mapping facilitates identification of mutations in consanguineous families with epidermolysis bullosa.

Autozygosity mapping (AM) is a technique utilised for mapping homozygous autosomal recessive (AR) traits and facilitation of genetic diagnosis. We investigated the utility of AM for the molecular diagnosis of heterogeneous AR disorders, using epidermolysis bullosa (EB) as a paradigm. We applied this technique to a cohort of 46 distinct EB families using both short tandem repeat (STR) and genome-wide single nucleotide polymorphism (SNP) array-based AM to guide targeted Sanger sequencing of EB candidate genes. Initially, 39 of the 46 cases were diagnosed with homozygous mutations using this method. Independently, 26 cases, including the seven initially unresolved cases, were analysed with an EB-targeted next-generation sequencing (NGS) panel. NGS identified mutations in five additional cases, initially undiagnosed due to the presence of compound heterozygosity, deep intronic mutations or runs of homozygosity below the set threshold of 2 Mb, for a total yield of 44 of 46 cases (95.7%) diagnosed genetically.

The elevated level of osteopontin in patients with pemphigus vulgaris: A cytokine-like protein with a therapeutic potential.

BACKGROUND: Pemphigus vulgaris (PV) is a life-threatening autoimmune disease with no certain treatment. Anticytokine therapy is being increasingly discussed in multiple autoimmune diseases. Osteopontin (OPN) is a glycoprotein produced by a variety of immune cells. Increased OPN serum levels have been reported in several autoimmune diseases, with targeting OPN considered as a promising therapy in these diseases. However, the role of OPN in PV has not been well studied so far. OBJECTIVE: To investigate whether OPN level is elevated in PV patients in the active stage of the disease and to examine its possible relationship with disease severity and anti-desmoglein (anti-Dsg) antibodies levels. MATERIALS AND METHODS: This study included 53 consecutive subjects affected by PV and 38 age- and sex-matched healthy controls. Clinical characteristics and Autoimmune Bullous Skin Disorder Intensity Score (ABSIS) were assessed. Serum OPN levels (pg/mL) and anti-Dsg antibodies were also measured. RESULTS: The serum OPN level of the patient group proved to be statistically higher than that of the control group (11.08 ± 5.24 vs 8.47 ± 5.68; p = .02). No significant relationship were detected between the serum OPN level and anti-Dsg1 or anti-Dsg3 antibodies (r = 0.1, p = .2 and r = 0.1, p = .4), respectively. In addition, no correlation was found between serum OPN levels and severity of PV as measured by ABSIS (r = 0.08 and p = .5). CONCLUSION: The growth observed in OPN levels in pemphigus patients suggests the role of OPN in pemphigus pathogenesis, but there is a need for more extensive studies to show how OPN can be associated with the PV pathogenesis and whether OPN could be used as an important therapeutic target in pemphigus disease.

Intralesional botulinum toxin-A injection for the treatment of multiple eccrine hidrocystomas.

BACKGROUND: Multiple eccrine hidrocystomas (MEH) are benign cystic lesions of the sweat gland ducts. They are characterized by translucent, skin-colored or bluish dome-shaped papules on the face, causing cosmetic concern. Recently, botulinum toxin-A, because of its antiperspirant properties, has been used to treat facial MEH. However, there are only some case reports in the literature. OBJECTIVE: Here, we conducted a prospective study to assess the efficacy and safety of intralesional injection of botulinum toxin-A (Dysport) for the treatment of MEH. MATERIAL AND METHODS: Twenty patients (3 men and 17 women), aged from 31 to 75 years old, participated in this study. A 300 unit vial of botulinum toxin-A (Dysport, Ipsenn Biopharm, United Kingdom) was diluted with 4 ml of saline solution without preservative to achieve a concentration of 7.5U/.1 ml. Up to 1.5 unit of botulinum toxin was injected intradermally at the base of each lesion to raise a visible wheal. The patients were evaluated 7 days later, and any clinical changes or adverse effects were recorded. RESULTS: In all patients, more than 75% of eccrine hidrocystoma lesions resolved without any scaring. The result sustained for 2-5 months. In two patients mild smile asymmetry and in one patient lagophthalmos were noted approximately 5-7 days after injection that gradually resolved in 3 weeks. CONCLUSION: Intralesional botulinum toxin-A for treatment of multiple hidrocystomas is a simple and well-tolerated procedure. It is accompanied by excellent results, a good postoperative course, and no risk of scarring. It can be considered in patients who did not respond to other treatment or even as the first line therapy.

No Relation between Psoriasis and Renal Abnormalities: A Case-Control Study.

Multiple observational studies have demonstrated that psoriasis is associated with nephropathy; however, the renal involvement in psoriasis remains largely a matter of debate. The current study was designed to investigate if psoriatic patients are at increased risk of renal abnormalities, in absence of any other comorbidities. Forty patients (11 women, 29 men, mean age 44.9 ± 15.45 years) with moderate to severe chronic plaque type psoriasis who were not under systemic therapy and 40 age- and gender-matched control subjects were enrolled in the study. Patients and controls with history of diabetes, hypertension, and chronic renal disease were excluded. Urinalysis by dipstick and microscopic evaluation and 24 h proteinuria and albuminuria were measured in all patients and controls. Patients with psoriasis and controls were not significantly different with respect to the prevalence of abnormal urinalysis (7.5% versus 5%, P = 1.0), mean 24 h proteinuria (70.40 ± 24.38 mg/24 h versus 89.40 ± 26.78 mg/24 h, P = 0.30), and albuminuria (14.15 ± 8.12 mg/24 h versus 16.62 ± 8.21 mg/24 h, P = 0.18). The presence of abnormal urinalysis was not more common in patients with psoriasis than in controls. Our study demonstrated that psoriatic patients without any other comorbidities are not at increased risk of kidney disease.

Multifocal epithelial hyperplasia: report of 3 cases.

Multifocal epithelial hyperplasia (MEH) is a rare disorder characterized by multiple painless discrete and soft flattened papules on the oral mucosa. It is caused by human papilloma virus 13 and 32. The frequency of this disease varies widely from one geographic region to another. Generally it is very rare in Asia. Herein we report 3 Iranian cases with oral lesions, which showed clinical and histopathological characteristics of MEH disease. Two of them were siblings and HPV13 was detected in one of the patients.