Dermoscopic findings and comparison of usefulness of longitudinal versus transversal sections in the histological diagnosis of alopecia X.

BACKGROUND: A combination of dermoscopic and histological findings may provide useful information for the diagnosis of hair follicle diseases. However, there are no studies on dermoscopic-histopathological correlations in dogs affected by alopecia X, and comparison of longitudinal versus transversal sectioning of skin biopsy specimens in the assessment of this hair loss disorder has not been thoroughly investigated. HYPOTHESIS/OBJECTIVES: The aim of this study was to correlate dermoscopic and histological features using both longitudinal and transversal sectioning of skin biopsy samples to gain additional information for the diagnosis of alopecia X. ANIMALS: Nineteen Pomeranian dogs affected by alopecia X and five healthy Pomeranians as controls. MATERIALS AND METHODS: Dermoscopic-histological correlation was performed within the diseased group, whereas histological comparisons against controls. The demographic and clinical characteristics also were related to the histological findings. RESULTS: The dermoscopic findings revealed scattered, thinned, short hairs mixed with amorphous keratoseborrhoeic-like material (follicular plugging), perifollicular and intrafollicular scaling, and hyperpigmentation varying from pinpoint black spots to a diffuse texture. Dermoscopic findings correlated with histological findings for selected qualitative and quantitative findings. The usefulness of transversal sections was demonstrated in accurately determining the hair follicular density and counts, growth arrest phases and in identifying mineralisation of hair follicle basement membrane when compared to the longitudinal. Conversely, no correlations between histological findings and demographic and clinical characteristics were detected. CONCLUSIONS AND CLINICAL RELEVANCE: These data provide evidence of the usefulness of dermoscopic evaluation as an accessory diagnostic tool and of transversal sections of skin biopsies as complementary to the diagnosis of alopecia X.

Heterozygous ATP2A2 missense variant identified in a Shih Tzu with Darier disease.

Darier disease is caused by heterozygous loss of function variants in the ATP2A2 gene encoding the endoplasmic/sarcoplasmic reticulum Ca2+ pump ATP2A2. Defective intracellular calcium signaling in the epidermis results in a loss of desmosomal adhesion and the development of characteristic skin lesions. In this study, we investigated a Shih Tzu that developed erythematous papules on the ventrum and, over time, the dorsal neck and a nodule in the right ear canal with secondary ear infection. Histopathologic examination demonstrated discrete foci of acantholysis affecting suprabasal layers of the epidermis. Whole genome sequencing of the affected dog identified a heterozygous missense variant, p.N809H, affecting an evolutionarily conserved amino acid residue of the ATP2A2 protein. The highly characteristic clinical and histopathologic findings together with a plausible variant in the only known functional candidate gene establish the diagnosis of canine Darier disease in the studied dog and highlight the potential of genetic analyses as complementary diagnostic approach in veterinary medicine.

A Case of Noonan Syndrome and Kyrle Disease: Casualty or Causality?

A 39-year-old Caucasian woman affected by Noonan Syndrome (NS) mutated in RAF1 was referred to us with itchy lesions on her limbs that had appeared two months earlier. Clinically, there were multiple umbilicated papules with a hyperkeratotic central plug, localized on the upper and lower limbs (Figure 1, a-b). The patient had no personal history of diabetes mellitus or chronic renal failure, but suffered from hypertrophic cardiomyopathy. Blood tests showed no abnormalities. On histological examination of a skin lesion, an ectatic hair follicle with a hyperkeratotic ostium was observed with fragments of hair, inflammatory cells, and epidermal perforation. A final diagnosis of Kyrle disease (KD) was established. The patient underwent narrowband UVB (NB-UVB) phototherapy with residual atrophic scars (Figure 1, c-d), but with a complete and long-lasting resolution of symptoms. KD belongs to perforating dermatoses (PD), a heterogeneous group of skin diseases characterized by the transepidermal elimination of dermal components. Despite the classification of PD still being under debate, four primary forms are traditionally recognized: reactive perforating collagenosis, elastosis perforans serpiginosum, perforating folliculitis, and KD (1). The typical skin manifestation of KD is an eruption of dome-shaped papules and nodules, with a whitish central keratotic plug, mainly localized on the extremities and the buttocks. Described by Kyrle in 1916, KD is frequently associated with systemic diseases, especially chronic renal failure and diabetes mellitus. Other associated conditions include chronic hepatic disease, internal malignancies, and congestive heart disease (1). Despite the absence of a consensus, the control of the underlying disease remains the first therapeutic target. Both topical (keratolytics, retinoids, and corticosteroids) and systemic treatments (corticosteroids, retinoids, antibiotics, and phototherapy) have been reported to control skin manifestations (2). In our experience, NB-UVB is an effective option as first-line therapy in case of diffuse lesions, both in KD and in other PD (3). NS is a relatively common RASopathy, a heterogenous group of genetic diseases characterized by a defect of the Ras-mitogen-activated protein kinase (Ras-MAPK) pathway, with an estimated prevalence of 1/1000-2500. PTPN11 is the most frequent mutated gene, accounting for 50% of cases, but more than ten genes have been identified as causing NS (4). Classical features include a distinctive facial dysmorphism, short stature, pulmonic stenosis, and other anomalies of different organs. The skin is commonly involved. Keratinization disorders and hair abnormalities such as keratosis pilaris, ulerythema ophryogenes, wavy or curly hair, and scarce scalp hair, are often described. Other cutaneous signs include easy bruising, skin hyperlaxity, multiple lentigines, and café-au-lait spots (5). To the best of our knowledge, no cases of KD in patients with NS have been previously reported to date. The exact etiopathogenesis of KD is not clear, but it has been hypothesized that systemic diseases, such as diabetes and chronic renal failure, can cause a deposit of substances or dermis alterations, which triggers the inflammatory process with subsequent transepidermal extrusion (1). In our patient, we ruled out all the causes commonly associated with KD. It is however possible that this manifestation could be a direct result of the patient's illness. Our patient suffered from diffuse keratosis pilaris, and an abnormal epidermal keratinization with a secondary inflammatory dermic response is among the suggested possible pathogenetic mechanisms of KD (1). On the other hand, the hyperlaxity and fragility of the skin typical of NS suggest the presence of altered connective tissue, which could trigger an abnormal keratinization and, subsequently, the transepidermal extrusion, as well as perforating elastosis, which is associated with genetic connective tissue diseases (1). Moreover, our patient suffered from a cardiac disease, another condition associated with KD (5). Although these explanations have their appeal, there is currently insufficient evidence of a link between KD and NS, and it will be necessary to collect additional data to confirm this hypothesis.

Treatment of keratosis pilaris and its variants: a systematic review.

INTRODUCTION: Keratosis pilaris (KP) is a common, benign skin condition of follicular hyperkeratosis. Although KP is asymptomatic, the cosmetic appearance of KP can lead to psychosocial distress among patients. New emerging treatments are increasingly being utilized. Yet, there is little to no summative data on the treatments of KP and its subtypes. OBJECTIVE: To summarize existing literature on treatments for KP and its subtypes. METHODS: A comprehensive search was performed using Pubmed/MEDLINE, Embase and Web of Science databases. The search identified 1150 non-duplicated articles, and 47 articles were included in the review. The primary outcomes measured were KP treatment type and the degree of improvement following therapy. FINDINGS: Our findings demonstrate that the most supported form of treatment for KP is laser therapy, particularly the QS:Nd YAG laser. Topical treatments - including Mineral Oil-Hydrophil Petrolat, tacrolimus, azelaic acid, and salicylic acid - are also effective at least for improving the appearance of KP. CONCLUSION: While the measured treatment outcomes varied among studies, laser therapy appears to be the most effective form of treatment. Use of topicals also improved KP lesions.

Light and Laser Treatments for Keratosis Pilaris: A Systematic Review.

BACKGROUND: Keratosis pilaris (KP) is a common hereditary keratinization disorder. Keratosis pilaris rubra and KP atrophicans faciei are less frequent variants of the disease. Topical treatments often yield ineffective and temporary results. OBJECTIVE: The objective of this article is to review and assess all the studies that used light and laser devices to treat KP and its variants. MATERIAL AND METHODS: On January 15, 2017, an online search of the MEDLINE, Embase, and Cochrane databases was performed using the following combination of keywords: "keratosis pilaris" and "treatment." RESULTS: Seventeen studies related to light and laser treatments were retained for analysis. The total number of treated patients was 175. Of which, 22 patients had KP atrophicans faciei, 17 patients had KP rubra, and 136 patients had KP. CONCLUSION: Light and laser devices have been emerging as promising therapeutic options for a disfiguring disease that still lacks, until today, an effective long-term treatment.

Ayurveda management of keratosis pilaris - a case report.

OBJECTIVES: Keratosis pilaris (KP) is the condition of the skin with extensive keratin follicular plugging. It may be associated with the erythema. The upper arm extensor area, shoulders, back of neck and thighs, as well as face and the upper trunk are the areas of presentation. Available medications for KP give only symptomatic relief, while some produce serious side effects. There is no proven universal treatment for the disease that can provide complete recovery. Ayurveda management of KP is not yet reported. CASE PRESENTATION: A 26-year-old male patient, presented with main complaints started with papular lesions over his right shoulder, chest and upper back along and later with pustular lesions in the past 2 weeks. The condition was associated with redness, mild swelling and itching. The case was diagnosed as Keratosis pilaris based on its presentation, site, and pathogenesis. Also by analyzing the extent of vitiation of dosas (morbidities), the Vata kapha pitta hara line of treatment was adopted, which was accomplished in two phases i. e. Sodhana Cikitsa and Samana Cikitsa. CONCLUSION: Both internal and external treatments along with diet restrictions were found effective in arresting the pathogenesis and recovery in a short period. All the symptoms associated with the condition were completely cured with no signs of re-occurrence.

The treatment of Kyrle's disease: a systematic review.

Kyrle's disease (KD) is a cutaneous disease that develops in individuals with underlying systemic disease, particularly chronic renal failure and diabetes mellitus (DM), and is associated with a high burden of disease linked to itch. The intensely pruritic, hyperkeratotic papulonodular rash seen in KD dramatically impairs patients' quality of life and increases their risk of mortality. Unfortunately, no guidelines or evidence-based regimens have been specifically developed for KD, making the treatment of this disease particularly challenging for physicians. This article aims to provide the first comprehensive, up-to-date overview and analysis of treatment options employed for KD. A search of the PubMed/MEDLINE and Scopus databases was performed for articles regarding the treatment of KD, published in English between 1990 and 2019. Seventy-three articles were identified, of which eighteen met the inclusion criteria. We discovered that a wide variety of treatment regimens for KD have been reported in the literature, including oral antibiotics, immunosuppressants, phototherapy, topical/systemic retinoids, topical keratolytics and various combination therapies, which include some of the aforementioned treatments, in conjunction with oral/topical/injectable steroids, emollients and/or antihistamines. The use of a combination regimen is the most commonly practiced therapeutic approach to KD. Topical corticosteroids and depot corticosteroid injections repeatedly appeared in many of the regimens encountered during our search. While no definitive recommendations can be made based on existing literature, this article provides physicians with a summative outline that can help guide management and be referenced when other treatment efforts fail. The increasing prevalence of renal disease, DM and other chronic diseases will inevitably lead to rising rates of KD in the upcoming years. While randomized controlled trials are greatly needed, novel antipruritic immunomodulatory drugs targeting specific interleukin receptors (IL-4/13/31) and intracellular signalling (e.g. Janus kinase) pathways may have a potential role in the treatment of this disease.

Grover disease: review of subtypes with a focus on management options.

Grover disease (GD) is a benign eruption that causes a papulovesicular rash on the trunk and proximal extremities. It often resolves spontaneously but can follow a more chronic and fluctuating course that may last several years. Although the etiology remains unknown, several associated triggers have been identified including heat and sweating, cool and dry air, renal failure, malignancy, and the initiation of several drugs. Since the disease tends to resolve on its own, management is aimed at disease prevention and symptomatic relief. First-line therapy includes topical steroids and vitamin D analogues with adjuvant antihistamines. In more severe cases that are refractory to less aggressive therapy, systemic corticosteroids, retinoids, and phototherapy may lead to successful resolution. Novel therapies are few and have little evidence but involve innovative use of light therapy and immune modulators. Herein, we review the literature and new trends of GD with a focus on established and novel treatments.

Innovative 1064-nm Nd:YAG Laser Significantly Improves Keratosis Pilaris, A Randomized, Double-Blind, Sham-Irradiation-Controlled Trial.

BACKGROUND AND OBJECTIVE: Keratosis pilaris (KP) is a common follicular disorder for which various topical agents and energy-based devices have been used with some efficacy. To evaluate the efficacy of a novel 1064-nm Nd:YAG laser for the reduction of skin roughness, erythema, and hyperpigmentation in KP subjects. STUDY DESIGN/MATERIALS AND METHODS: Twenty-three subjects with untreated KP on the upper outer arms participated in a randomized, single-blind fashion. One arm of each subject was divided into upper and lower parts. One part was randomized to be treated with an innovative 1064-nm Nd:YAG laser, while the other part received sham irradiation. Subjects received four consecutive treatments at 4-week intervals. Antera3D was used to measure skin roughness, erythema, and hyperpigmentation at baseline and 4 weeks after the last treatment. Moreover, clinical outcomes were also evaluated by subjects' Global Improvement Score (GIS) and subjects' satisfaction grading scores. RESULTS: Twenty-three subjects completed the study. There was statistically significant reduction of skin roughness measured by Antera3D compared with control group (P < 0.001). There were statistically significant improvements of skin roughness, erythema, hyperpigmentation, and overall appearances graded by subjects' Global Improvement Score (P < 0.001 all). Subjects' satisfaction scores were graded significantly better in treatment parts (P < 0.001). No adverse events including burning, bulla, erosion, post-inflammatory hyper/hypopigmentation, and scar formation developed in any subjects throughout the study period. CONCLUSION: This innovative 1064-nm Nd:YAG laser has proved to significantly and safely reduce skin roughness in Thai KP subjects compared with control after four sessions. Lasers Surg. Med. © 2019 Wiley Periodicals, Inc.

Keratosis Pilaris and its Subtypes: Associations, New Molecular and Pharmacologic Etiologies, and Therapeutic Options.

Keratosis pilaris is a common skin disorder comprising less common variants and rare subtypes, including keratosis pilaris rubra, erythromelanosis follicularis faciei et colli, and the spectrum of keratosis pilaris atrophicans. Data, and critical analysis of existing data, are lacking, so the etiologies, pathogeneses, disease associations, and treatments of these clinical entities are poorly understood. The present article aims to fill this knowledge gap by reviewing literature in the PubMed, EMBASE, and CINAHL databases and providing a comprehensive, analytical summary of the clinical characteristics and pathophysiology of keratosis pilaris and its subtypes through the lens of disease associations, genetics, and pharmacologic etiologies. Histopathologic, genomic, and epidemiologic evidence points to keratosis pilaris as a primary disorder of the pilosebaceous unit as a result of inherited mutations or acquired disruptions in various biomolecular pathways. Recent data highlight aberrant Ras signaling as an important contributor to the pathophysiology of keratosis pilaris and its subtypes. We also evaluate data on treatments for keratosis pilaris and its subtypes, including topical, systemic, and energy-based therapies. The effectiveness of various types of lasers in treating keratosis pilaris and its subtypes deserves wider recognition.

Treatment of keratosis pilaris with 810-nm diode laser: a randomized clinical trial.

IMPORTANCE: Keratosis pilaris (KP) is a common skin disorder of follicular prominence and erythema that typically affects the proximal extremities, can be disfiguring, and is often resistant to treatment. Shorter-wavelength vascular lasers have been used to reduce the associated erythema but not the textural irregularity. OBJECTIVE: To determine whether the longer-wavelength 810-nm diode laser may be effective for treatment of KP, particularly the associated skin roughness/bumpiness and textural irregularity. DESIGN, SETTING, AND PARTICIPANTS: We performed a split-body, rater-blinded, parallel-group, balanced (1:1), placebo-controlled randomized clinical trial at a dermatology outpatient practice of an urban academic medical center from March 1 to October 1, 2011. We included all patients diagnosed as having KP on both arms and Fitzpatrick skin types I through III. Of the 26 patients who underwent screening, 23 met our enrollment criteria. Of these, 18 patients completed the study, 3 were lost to or unavailable for follow-up, and 2 withdrew owing to inflammatory hyperpigmentation after the laser treatment. INTERVENTIONS: Patients were randomized to receive laser treatment on the right or left arm. Each patient received treatment with the 810-nm pulsed diode laser to the arm randomized to be the treatment site. Treatments were repeated twice, for a total of 3 treatment visits spaced 4 to 5 weeks apart. MAIN OUTCOMES AND MEASURES: The primary outcome measure was the difference in disease severity score, including redness and roughness/bumpiness, with each graded on a scale of 0 (least severe) to 3 (most severe), between the treated and control sites. Two blinded dermatologists rated the sites at 12 weeks after the initial visit. RESULTS: At follow-up, the median redness score reported by the 2 blinded raters for the treatment and control sides was 2.0 (interquartile range [IQR], 1-2; P = .11). The median roughness/bumpiness score was 1.0 (IQR, 1-2) for the treatment sides and 2.0 (IQR, 1-2) for the control sides, a difference of 1 (P = .004). The median overall score combining erythema and roughness/bumpiness was 3.0 (IQR, 2-4) for the treatment sides and 4.0 (IQR, 3-5) for the control sides, a difference of 1 (P = .005). CONCLUSIONS AND RELEVANCE: Three treatments with the 810-nm diode laser may induce significant improvements in skin texture and roughness/bumpiness in KP patients with Fitzpatrick skin types I through III, but baseline erythema is not improved. Complete treatment of erythema and texture in KP may require diode laser treatment combined with other laser or medical modalities that address redness. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01281644.

Significant alleviation of Darier's disease with fractional CO2 laser.

Darier's disease (DD) is a dominantly inherited genodermatosis with highly variable expression. It is characterized by symmetrical hyperkeratotic papules affecting seborrheic areas and extremities. The existence of unsightly lesions could lead to discomfort and social handicap. Conventional treatment consists of topical and systemic steroids and/or retinoids alleviating DD. Ablative lasers also have been used to treat these conditions with variable results and side effects. To the best of our knowledge, fractional CO2 laser has never been used to treat DD. We present a case of a 36-year-old woman with verrucous and hyperkeratotic plaques of the forehead significantly improved after two sessions of fractional CO2 laser treatment. Neither scars nor pigmentary disorders were noted.

Role of bath psoralen plus ultraviolet A in early-stage mycosis fungoides.

BACKGROUND: Psoralen plus ultraviolet (UV) A (PUVA) radiation is the preferred treatment for folliculotropic mycosis fungoides (MF) and MF refractory to narrowband (NB) UVB radiation. However, systemic PUVA has many unfavorable side effects and contraindications. Bath PUVA has been found to be a suitable alternative in patients with psoriasis, but data on MF are sparse. OBJECTIVE: The purpose of the study was to evaluate the effectiveness of bath PUVA in the treatment of folliculotropic MF and NB-UVB-refractory early-stage MF. METHODS: The study group included 26 patients of average age 44 years attending a tertiary medical center in 2004 through 2012, 14 with folliculotropic type and 12 with NB-UVB-refractory early-stage MF who were not amenable for oral PUVA. Treatment consisted of 0.2 mg/L 8-methoxypsoralen bath 3 times weekly followed by UVA irradiation at 0.3 J/cm(2) with fixed increments every second session. RESULTS: A complete clinical response was achieved in 62% of patients after an average of 33 weeks and a cumulative radiation dose of 158 J/cm(2). LIMITATIONS: This was a relatively small series. CONCLUSION: Bath PUVA is a good treatment option for superficial folliculotropic MF and NB-UVB-refractory early-stage MF.

Ulerythema ophryogenes: updates and insights.

Ulerythema ophryogenes is a rare cutaneous atrophic disorder that occasionally is associated with Noonan syndrome, de Lange syndrome, Rubinstein-Taybi syndrome, and cardiofaciocutaneous (CFC) syndrome. Often presenting in pediatric patients, the pathogenesis of ulerythema ophryogenes remains unclear, though several genetic causes have been suggested. Treatment recommendations remain anecdotal, but clearance has been noted as the patient ages. Although topical agents have been the mainstay of therapy, recent advancement in laser intervention for treatment of ulerythema ophryogenes is promising.

Photopneumatic therapy for the treatment of keratosis pilaris.

BACKGROUND: Current treatment options for keratosis pilaris (KP) are limited and are often found to be unsatisfactory to patients. OBJECTIVE: Pilot study to determine if photopneumatic therapy (PPx) can improve the erythema and skin texture in KP. METHODS: Ten patients with KP were treated with one session of PPx on the upper arm and then evaluated one month later for treatment efficacy. RESULTS: Average investigator-assessed improvement was 27% in erythema and 56% in skin texture roughness. Average patient self-reported improvement was 52% in erythema and 53% in skin texture. The mean satisfaction score was 6.3 on a scale of 1 to 10 (median 7.5) and 8 out of 10 participants reported they would choose to receive PPx for their KP again in the future. LIMITATIONS: Small number of patients, short follow-up period, and lack of blinding of the examiner and the patients making recall bias possible. CONCLUSIONS: One treatment of PPx improved both the erythema and redness associated with KP over at least a one month period.

Local hyperthermia treatment of extensive viral warts in Darier disease: a case report and literature review.

BACKGROUND: Darier disease is an autosomal dominant hereditary skin disease that is susceptible to secondary bacterial or fungal infections, but rarely to human papillomavirus (HPV) infections. Multiple or extensive warts from HPV remain a therapeutic challenge, but local hyperthermia is effective. We treated a patient with Darier disease who had superimposed warts in the genital and neck regions. MATERIALS AND METHODS: The patient was treated with tolerable local hyperthermia with infrared light from a halogen lamp (surface temperature, 40°C) to a single target lesion on the genitalia (30 min daily) for 3 consecutive days. RESULTS: Within 2 weeks, the target lesion cleared and synchronous regression of untreated lesions on the neck was observed. CONCLUSIONS: In Darier disease, local hyperthermia treatment of HPV warts in 1 region was effective in treating multiple lesions, including lesions at a remote site, possibly by promoting an immune response against HPV.

Treatment of pigmented keratosis pilaris in Asian patients with a novel Q-switched Nd:YAG laser.

BACKGROUND: Treatment for most cases of keratosis pilaris requires simple reassurance and general skin care recommendations. Many Asian patients find lesions due to pigmented keratosis pilaris to be cosmetically unappealing. Treatment of post-inflammatory hyperpigmentation using a 1064-nm Q-switched Nd:YAG laser with low fluence is reported. OBJECTIVE: To investigate the efficacy of a novel Q-switched Nd:YAG laser for the treatment of pigmented keratosis pilaris in Asian patients. METHODS: Ten patients with pigmented keratosis pilaris underwent five weekly treatments using a Q-switched Nd:YAG laser (RevLite(®); HOYA ConBio(®), Freemont, CA, USA) at 1064 nm with a 6-mm spot size and a fluence of 5.9 J/cm(2). Photographic documentation was obtained at baseline and 2 months after the final treatment. RESULTS: Clinical improvement was achieved in all 10 patients with minimal adverse effects. CONCLUSION: For the treatment of keratosis pilaris, the use of a Q-switched Nd:YAG laser can be helpful for improving cosmetic appearance as it can improve pigmentation.

[Segmental Darier disease : treatment with pulsed dye laser]. / Segmentaler Morbus Darier : Behandlung mit dem gepulsten Farbstofflaser.

Darier disease is often associated with pruritus and an unpleasant odor, causing medical and emotional problems. Ablative laser therapy has proven effective in ameliorating these symptoms. Side effects of this approach include permanent hypopigmentation and a risk of scarring. We present two cases where non-ablative therapy with pulsed dye lasers proved a safe and effective way to manage the intertriginous lesions. Although the mechanism of action is unclear, our success indicates that pulsed dye laser therapy is an option in Darier disease. Larger numbers of patients, ideally in multicenter studies, must be treated in this way to confirm our results.