Netherton Syndrome: Case Report and Review of the Literature.

Netherton syndrome (NS) is a rare genodermatosis with an autosomal recessive pattern of inheritance caused by pathogenic variants in the SPINK5 gene. It is characterized by a triad consisting of atopic diathesis, ichthyosis linearis circumflexa, and hair shaft abnormalities. Ichthyosis linearis circumflexa can be confused with atopic dermatitis leading to a delayed diagnosis. Furthermore, difficulty in making the differential diagnosis with other atopiform, erythrodermic, and ichthyosiform entities that exhibit hair shaft abnormalities represent a challenge. Trichoscopy is an accessible and noninvasive auxiliary diagnostic tool in these cases; the hair shaft abnormalities found in NS are bamboo, golf tee, and matchstick hairs. Identification of a pathogenic variant in the SPINK5 gene through genetic testing is necessary to confirm the diagnosis. Multiple treatment options are available including topical therapy with emollients, corticosteroids, calcineurin inhibitors, antiseptics, and narrowband UVB phototherapy. Systemic treatments comprehend intravenous immunoglobulins, and advances in the understanding of the pathophysiology of NS have led to more directed therapies with biologics such as infliximab, ixekizumab, secukinumab, ustekinumab, and dupilumab. Treatments currently under investigation include inhibitors of kallikrein 5, cathelicidins, drugs activating the transcription factor nuclear factor erythroid-derived 2-like 2, and gene therapy using autologous keratinocytes induced with a lentiviral vector encoding SPINK5.

Updates and new medical treatments for vitiligo (Review).

Vitiligo is a multifactorial disease characterized by the loss of skin pigment, which results in achromic macules and patches. There are currently several medical treatments available, which aim to arrest progression and induce skin repigmentation. These treatments alone or combined have exhibited varying degrees of pigmentation, and the majority are safe and effective. All therapies for vitiligo are limited, and no known treatment can consistently produce repigmentation in all patients. Individualized treatment is appropriate according to the location, clinical presentation and the presence of disease activity. The present review summarizes the medical treatments available for vitiligo: Systemic and topic pharmacological therapies, physical and depigmentation treatments. Several treatments are still underway and have not yet been approved. However, due to the promising preliminary results, these are also mentioned in the present review.

Cryotherapy plus low-dose oral isotretinoin vs cryotherapy only for the treatment of anogenital warts: a randomized clinical trial.

BACKGROUND: Anogenital warts are a common human papillomavirus infection. They cause emotional distress, especially when they are in the anogenital region. Cryotherapy is a first-line treatment. Previous clinical trials and case series have reported variable results with retinoids (isotretinoin) as adjuvant therapy. OBJECTIVE: To determine the safety and efficacy of low-dose oral isotretinoin as adjuvant treatment of anogenital warts. METHODS: Forty-six patients with anogenital warts were randomly assigned to isotretinoin + cryotherapy (n = 23) or only cryotherapy (n = 23). Patients were allocated via an interactive web-based randomization system. Evaluators were blinded to treatments. Isotretinoin 20 mg/daily + cryotherapy or cryotherapy were prescribed for 6 weeks. Patients were followed for 4 months. Genotyping of lesions was performed before treatment started. Dermatology Life Quality Index (DLQI) and Columbia-Suicide Severity Rating Scale (C-SSRS) were measured at the beginning and end of therapy. All patients completed the study. RESULTS: Both Groups had 50% clearance at the end of treatment. Recurrence in the combined group was not significantly lower than in the cryotherapy group (P = 0.59). Improvement was observed in the DLQI of all patients in both groups (P = 0.001). No suicidal intention was detected with the C-SSRS. Two patients (one in each group) had liver function test abnormalities after treatment. CONCLUSION: Combined therapy showed a slight not significant efficacy for anogenital warts in Hispanic patients. Low-dose isotretinoin seems to be safe even when it is used with cryotherapy on anogenital warts. TRIAL REGISTRATION: On April 25, 2019 with registration number DE19-00004, CONBIOÉTICA-19-CEI-001-20160404. Prospectively registered.

Micro needling: A novel therapeutic approach for androgenetic alopecia, A Review of Literature.

Androgenetic alopecia (AGA) is an androgen-dependent hereditary trait resulting in hair miniaturization. It is the most common type of alopecia in men and women. During the last years, multiple treatment modalities have been studied, but only topical minoxidil and finasteride have been approved by the US Food and Drug Administration. Microneedling (MN) is a minimally invasive technique that induces collagen formation, as well as growth factors production and neovascularization. Even though not many studies of MN in alopecia have been performed, it remains a favorable treatment modality; however, no standardized protocol for MN in hair loss has been proposed yet. Current evidence is not sufficient to allow a direct comparison with other therapies, but it shows promises to increase hair density, thickness, and quality of hair, especially when combined with other treatments or when used as a drug delivery system. This article aims to summarize the available literature regarding the use of MN alone or associated with other therapies for the treatment of androgenetic alopecia.

Expression of melanocortin 1 receptor before and after narrowband UVB phototherapy treatment in patients with stable vitiligo: A prospective study.

Vitiligo is a disease characterized by skin depigmentation caused by the selective destruction of melanocytes. The melanocortin system participates as a regulator of melanogenesis and skin pigmentation. Narrowband UVB phototherapy (nb-UVB) is currently considered to be the gold standard and first choice treatment method for vitiligo vulgaris. The aim of the present study was to analyze the clinical and biochemical parameters of vitiligo, as well as to determine the expression of proopiomelanocortin (POMC), melanocortin 1 receptor (MC1R) and melanocortin 4 receptor (MC4R) genes in the skin of patients with stable vitiligo receiving nb-UVB phototherapy. Patient clinical and biochemical parameters, and the skin biopsies of 22 patients with stable vitiligo were analyzed. These biopsies were obtained before and after nb-UVB phototherapy. The genetic expression analysis of POMC, MC1R and MC4R genes was performed via RNA-Sequence analysis. A statistical evaluation of the clinical and biochemical parameters, the degree of response to treatment and the expression profiles of the melanocortin system genes were performed to identify their association with treatment response. A two-sided P≤0.05 value was considered to indicate a statistically significant difference. Alterations were observed in the expression profiles of MC1R following nb-UVB phototherapy (P≤0.05). In addition, elevated levels of triiodothyronine were associated with a poor response to nb-UVB phototherapy. In conclusion the current study revealed that nb-UVB phototherapy altered the expression profile of the MC1R gene.

Local secretion of stress hormones increases in alopecia areata lesions after treatment with UVA-1 phototherapy.

Alopecia areata (AA) is an autoimmune disease of the hair follicle. Keratinocytes of the hair follicle generate an immunosuppressive environment by the local secretion of hormones of the hypothalamic-pituitary-adrenal axis of the skin (skin HPA analog). Our objective was to measure the local production of corticotropin-releasing hormone (CRH), adrenocorticotropic hormone (ACTH), and α-melanocyte-stimulating hormone (α-MSH) in the scalp tissue of patients with AA before and after ultraviolet A1 (UVA-1) phototherapy to determine their role in the pathogenesis of AA and the effect of UVA-1 on the AA hormonal environment. This was a retrospective and descriptive study of skin samples from 22 patients with AA before and after UVA-1 treatment. We compared the changes in the local hormonal environment by measuring CRH, ACTH, type 2 melanocortin receptor (ACTH receptor) and α-MSH with immunohistochemical stains. The positivity of MSH was significantly higher (P = .037) in the post-treatment samples compared with the baseline value. ACTH was significantly higher in intensity (P = .032) in the post-treatment samples compared with the initial value. CRH was significantly higher in intensity (P = .013) in baseline samples compared with the final biopsies. The positivity of the ACTH receptor MC2R was not different between the two groups (P = .626). In AA, an interruption in the signalling of CRH could decrease the local concentration of ACTH and MSH, and consequently, the immunosuppressive effect of these hormones. This phenomenon is normalized in the skin treated with UVA-1. A defective signalling system in the cutaneous HPA axis may be involved in the pathogenesis of AA.

Evaluation of skin expression profiles of patients with vitiligo treated with narrow-band UVB therapy by targeted RNA-seq

Abstract: Background: Vitiligo is characterized by a lack of pigmentation in the skin. To date, there are no studies that analyze the changes in gene expression in the skin of vitiligo patients in response to narrow-band ultraviolet B (nb-UVB) phototherapy treatment. Objective: Explore the usefulness of new generation RNA sequencing in the identification of gene expression changes in the skin of vitiligo patients treated with nb-UVB phototherapy. Methods: Four skin biopsies (4mm in diameter) were collected from 45 Mexican vitiligo vulgaris patients, 2 specimens before and 2 after treatment with nb-UVB phototherapy, obtained from pigmented and non-pigmented tissue. RNA extracted from the biopsies was analyzed using the Illumina TruSeq Targeted RNA Expression protocol to study the expression of genes that participate in pathways of skin homeostasis. The 2 groups were compared using Student's t-test and the Mann-Whitney U-test. Results: The expression analysis identified differences in 12 genes included in this study after comparing the samples obtained before and after treatment: 5 genes involved in skin pigmentation, 2 genes involved in apoptosis, 2 genes involved in cell survival, 2 genes involved in oxidative stress responses and 1 gene involved in signal transduction mechanisms (p<0.05). Study limitations: The small size of skin biopsies limits the amount of RNA obtained, the number of genes to be analyzed and the use of conventional techniques such as RT-qPCR. Conclusion: We demonstrated usefulness of new generation RNA sequencing in the identification of gene expression changes, in addition to identifying new targets in the study of vitiligo.

Evaluation of skin expression profiles of patients with vitiligo treated with narrow-band UVB therapy by targeted RNA-seq.

BACKGROUND: Vitiligo is characterized by a lack of pigmentation in the skin. To date, there are no studies that analyze the changes in gene expression in the skin of vitiligo patients in response to narrow-band ultraviolet B (nb-UVB) phototherapy treatment. OBJECTIVE: Explore the usefulness of new generation RNA sequencing in the identification of gene expression changes in the skin of vitiligo patients treated with nb-UVB phototherapy. METHODS: Four skin biopsies (4mm in diameter) were collected from 45 Mexican vitiligo vulgaris patients, 2 specimens before and 2 after treatment with nb-UVB phototherapy, obtained from pigmented and non-pigmented tissue. RNA extracted from the biopsies was analyzed using the Illumina TruSeq Targeted RNA Expression protocol to study the expression of genes that participate in pathways of skin homeostasis. The 2 groups were compared using Student's t-test and the Mann-Whitney U-test. RESULTS: The expression analysis identified differences in 12 genes included in this study after comparing the samples obtained before and after treatment: 5 genes involved in skin pigmentation, 2 genes involved in apoptosis, 2 genes involved in cell survival, 2 genes involved in oxidative stress responses and 1 gene involved in signal transduction mechanisms (p<0.05). STUDY LIMITATIONS: The small size of skin biopsies limits the amount of RNA obtained, the number of genes to be analyzed and the use of conventional techniques such as RT-qPCR. CONCLUSION: We demonstrated usefulness of new generation RNA sequencing in the identification of gene expression changes, in addition to identifying new targets in the study of vitiligo.

A Case of Bullous Morphea Resistant to Methotrexate and Phototherapy Successfully Treated With Mycophenolate Mofetil.

Bullous morphea is rare clinical variant of localized scleroderma characterized by the formation of bullae on sclerotic morphea plaques. Severe disease may be highly disabling and greatly impair quality of life. Current treatment strategies are based on anecdotal reports of clinical experience and include topical corticosteroids, methotrexate and phototherapy. Herein, we describe the case of a 56-year-old woman with progressive bullous sclerotic lesions who was successfully treated with mycophenolate mofetil after treatment failure with psoralen plus ultraviolet A therapy, ultraviolet A1 phototherapy, and methotrexate. Treatment with mycophenolate mofetil halted disease progression after 8 weeks. No major adverse effects were recorded in a 3-year follow-up with continuous treatment. This case suggests mycophenolate mofetil may be considered as an alternative for the treatment of resistant bullous morphea lesions. J Drugs Dermatol. 2018;17(10):1123-1125.

Escalating dosimetry of UVA-1 in the treatment of alopecia areata.

BACKGROUND: Phototherapy can be an option in unresponsive alopecia areata (AA); however, variable results have been reported with its use. We could not find literature of treatment with UVA-1 in AA. A study was designed to evaluate progressive dosimetry to determine the initial dose and its increments. METHODS: Patients with unresponsive AA were recruited. Twenty-five sessions of 30 J/cm2 were administered. If hair regrowth was <75%, the dose was escalated to 60 J/cm2 . If hair improvement remained <75%, an additional 25 sessions at 120 J/cm2 were indicated. If total hair regrowth occurred before 75 sessions, a final visit was performed for biopsies and severity of alopecia tool (SALT) evaluation. Clinical and histopathological assessments were performed blindly. Adverse effects were recorded. RESULTS: Nine men and 13 women were included; 16 were initially S1 , one S3 , and five S4 . Median age was 32 years and median evolution 10 months. Nine patients achieved an S0 , eight S1 , and five S4 (P = 0.005). The most notable improvement was with 60 J/cm2 (P = 0.02). Biopsies exhibited an absence of inflammation in five patients and mild persistence in 17. An increase of 43.75% in anagen hairs (P ≤ 0.001) was achieved, telogen hairs decreased 16.3% (P = 0.06), and catagen hairs were reduced 22.7% (P = 0.005). Pearson's correlation was -0.82 and P ≤ 0.001, when correlating anagen hairs with final SALT. Improvement has continued for 6 months post treatment. Mild xerosis was observed in all patients, and six (28.6%) developed transient mild hyperpigmentation. CONCLUSIONS: This study provides a basis for UVA-1 dosimetry evaluating its therapeutic value in AA.

The prophylactic use of a topical scar gel containing extract of Allium cepae, allantoin, and heparin improves symptoms and appearance of cesarean-section scars compared with untreated scars.

BACKGROUND: Abdominal Cesarean sections (C-sections) are frequently associated with an increased risk of excessive or unpleasant scarring. A topical scar gel containing extract of Allium cepae, allantoin and heparin (Contractubex®; Merz Pharmaceuticals GmbH, Germany), has shown efficacy in improving the appearance of various scar types. OBJECTIVE: To investigate the efficacy of the topical scar gel, Contractubex, in the early treatment of C-section scars. MATERIALS & METHODS: A total of 61 females, aged ≥18 years, who had given birth by elective C-section for the first time within the last 5-10 days, were included in this prospective, randomized, single-center study. Patients were advised to apply the topical scar gel twice daily (treatment group), or received no treatment (control group). Efficacy was evaluated at 6 and 12 weeks after a baseline visit using the Patient and Observer Scar Assessment Scale (POSAS), a validated scar assessment tool comprised of a Patient Scale and an Observer Scale. RESULTS: Analysis revealed a significant change in the POSAS Patient Scale total score, with a 14.2% improvement in the treatment group compared with a decline of similar magnitude (-14.8%) in the control group at week 6. Significant improvements were also seen for POSAS Patient Scale sub-items in the treatment group compared with the control group for scar color (13.6% vs -18.5%, respectively, P=0.0284), stiffness (12.5% vs -34.6%, respectively, P=0.0029), and irregularity (29.4% vs -46.2%, respectively, P=0.0140) after 6 weeks of treatment. No significant changes were observed for the POSAS Observer Scale total score or its subitems after treatment with the topical scar gel, although there was a strong overall trend in favor of the treatment group. No significant adverse events were observed during the study. CONCLUSION: Contractubex represents an efficacious and well-tolerated preventative treatment that rapidly and significantly improves the color, stiffness and irregularity of C-section scars.

Therapeutic evaluation of UVB-targeted phototherapy in vitiligo that affects less than 10% of the body surface area.

BACKGROUND: Current treatments for vitiligo include different therapeutic modalities, such as corticosteroids, immunomodulators, pseudocatalase, skin grafts, diverse types of phototherapy [ultraviolet B (UVB), psoralen plus UVA (PUVA), narrow-band UVB (NB-UVB)], and, recently, targeted phototherapy. After a literature search, we found only two studies using different targeted broad-band UVB units for the treatment of vitiligo. OBJECTIVE: To evaluate the repigmentation response induced with broad-band, UVB-targeted phototherapy used as monotherapy in patients with vitiligo affecting less than 10% of the skin surface. METHODS: Twelve patients were recruited for treatment with 30 sessions of UVB-targeted phototherapy administered twice weekly. The assessment of repigmentation was made from a comparison of baseline photographs with those after 30 sessions by two independent investigators. Morphometric analysis was performed using a computer program. RESULTS: Repigmentation with an average of 66.25% was obtained on lesions of the face, and of 31.5% on the neck, trunk, and genitalia. On the extremities, there was no repigmentation. Itching, a burning sensation, erythema, desquamation, and transitory hyperpigmentation were observed in some patients. Minimal blistering and ulceration were observed in one patient. CONCLUSION: Targeted UVB phototherapy seems to be effective for the repigmentation of vitiligo in lesions located on the face, to a lesser degree on the trunk, and with no response in acral lesions; there were minimal adverse effects that did not require discontinuation of treatment.

[Biologic therapy: a new and promising option to treat psoriasis]. / Nueva y prometedora opción en psoriasis: la terapla biológica.

The histologic and immunologic findings on psoriasis have led to the development of biologic therapies for its treatment. Biologic therapies are classified according to their structure as recombinant human proteins, monoclonal antibodies, and fusion proteins. Currently there are five biological drugs approved by the Food and Drug Administration for the treatment of psoriasis; however research studies are being performed to implement a few others. It is important to be familiarized with biological drugs, understand their mechanisms of action, and their adverse effects in order to be able to provide patients the most adequate therapeutical alternative. Advances in biotechnology provide new strategies that act on the immune system. The clinical experience using biological therapies in dermatology is relatively limited and there is a need to define which patients are candidates to receive these drugs. The combination of biologic treatments with traditional drugs needs further research since this could enhance their benefits, limit their toxicity, and reduce costs.