Evaluation of a Moisturizing Cream with 20% Urea for Keratosis Pilaris.

BACKGROUND: Keratosis pilaris (KP) is a benign dermatosis consisting of folliculocentric keratotic papules or pustules with surrounding erythema, often on proximal extensor surfaces of extremities. Management strategies for KP largely center on moisturization and exfoliation. Urea, a well-established ingredient in topical skincare, is a component of the natural moisturizing factors with concentration-dependent humectant, emollient, and exfoliative properties.  Given the overlap of urea’s properties and management goals of KP, a 4-week, open-label, noncomparative clinical study was conducted to evaluate a moisturizing cream formulated with 20% urea for use in KP.  Thirty participants aged 18 to 65 years with KP completed this study. After a 5-day washout period, study participants applied a 20% urea cream once daily to areas of KP for 4 weeks. At baseline, 1-week, and 4-week visits, clinical grading of skin texture, adverse event monitoring, and participant satisfaction questionnaires were conducted. After 1 week and 4 weeks of product use, the percent change in skin smoothness/texture from baseline was significant (P≤0.001). Furthermore, after 4 weeks of use, the majority of participants indicated satisfaction with the feel of their skin, as well as improved confidence and decreased embarrassment related to their skin. No significant adverse events were reported. Overall, the results of this study support that 20% urea cream is generally well tolerated and suitable for use in treating KP. J Drugs Dermatol. 2024;23(1):1274-1277.     doi:10.36849/JDD.7806.

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.

Keratosis Pilaris Treatment: Evidence from Intervention Studies.

Keratosis pilaris is a common dermatosis observed in daily dermatologic practice. The diagnosis is clinical and usually asymptomatic, although sometimes patients may complain of mild pruritus and its cosmetic appearance. Few reports exist about its treatment. There are clinical trials assessing topical treatments and laser surgery, but no systematic reviews on its management were found in literature. An online research was conducted to identify evidence-based recommendations. Lactic acid, salicylic acid, and the 1064-nm Nd:YAG laser seem to be the most effective and safe treatment options for keratosis pilaris among patients aged 12 years and older; however, high-quality randomized controlled trials with long-term outcomes are required. (SKINmed. 2022;20:258-271).

Case report: Grönblad-Strandberg syndrome.

Objective: To present a case of secondary type 2 choroidal neovascularization (CNV) and exudative maculopathy in a patient with Grönblad-Strandberg syndrome. Methods: A 37-year-old male was admitted with bilateral progressive painless visual acuity loss and metamorphopsias. A thorough ophthalmologic and clinical examination was performed. Results: Best-corrected visual acuity (BCVA) on presentation was 20/ 200 OD (Oculus Dexter) and 20/ 60 OS (Oculus Sinister). Fundus examination revealed angioid streaks and subretinal hemorrhages on OU (Oculus Uterque), macular fibrosis on OD and "peau d'orange" pigmentary mottling on OS. Leakage areas on fundus fluorescein angiography (FFA) revealed active CNV on OU, which was confirmed by Optical Coherence Tomography (OCT). The presence of typical "plucked chicken" skin lesions in the latero-cervical area and their biopsy confirmed the diagnosis of Pseudoxanthoma elasticum (PXE). Consequently, the diagnosis of Grönblad-Strandberg syndrome was established. Conclusions: Every new diagnosis of angioid streaks entails not only a thorough ophthalmologic evaluation for secondary sight-threatening complications, but also a multidisciplinary evaluation due to the possibility of severe underlying systemic disease. Abbreviations: BM = Bruch's membrane, RPE = Retinal Pigmented Epithelium, PXE = Pseudoxanthoma Elasticum, ABCC6 = ATP binding cassette subtype C number 6, CNV = Choroidal Neovascularization, BCVA = Best-Corrected Visual Acuity, OD = Oculus Dexter, OS = Oculus Sinister, OU = Oculus Uterque, FFA = Fundus Fluorescein Angiography, OCT = Optical Coherence Tomography, IPO = Intraocular Pressure, ECG = Electrocardiogram, anti-VEGF = anti-vascular endothelial growth factor.

Clinical and Dermoscopic Evaluation of Trichloroacetic Acid 20% Versus Long-Pulsed 1064-nm Nd-YAG Laser in the Treatment of Keratosis Pilaris.

BACKGROUND: Keratosis pilaris (KP) is a common disorder of keratinization with different therapeutic modalities; however, none of them is completely satisfactory. OBJECTIVE: Assess and compare the efficacy of trichloroacetic acid (TCA) 20% and long-pulsed 1,064-nm Nd:YAG laser in the treatment of KP. MATERIALS AND METHODS: Twenty patients with symmetrically distributed areas of KP were enrolled in this study. In each patient, 2 symmetrical KP areas were randomly assigned to receive 4 sessions of either long-pulsed Nd:YAG laser or TCA 20%. Clinical evaluation by Investigator Global Assessment (IGA) was done by 2 blinded physicians after treatment. Dermoscopic assessment was done at baseline and at the end point of the study. RESULTS: Investigator Global Assessment of laser-treated area showed that 2 patients (10%) had moderate improvement, 10 patients (50%) had marked improvement, and 8 patients (40%) had excellent improvement. Investigator Global Assessment of TCA-treated area showed that 9 patients (45%) had marked improvement and 11 patients (55%) had excellent improvement. Dermoscopic score of KP showed a significant reduction with both modalities. The IGA and reduction in dermoscopic scores were comparable between the 2 modalities. CONCLUSION: Both long-pulsed 1,064-nm Nd:YAG laser and 20% TCA are effective in the treatment of KP. CLINICAL TRIAL REGISTRATION: Name of the trial register: clinicaltrial.gov . Registration number: NCT04797663.

Comparative study of the efficacy of fractional Er: YAG 2940 nm laser and Q-switched Nd: YAG 1064 nm laser in keratosis pilaris.

BACKGROUND: Keratosis pilaris is a common keratinization disorder of the extensor surfaces of the proximal extremities. Various treatment modalities reduce symptoms, but their efficacy is limited. AIMS: The aim of this study is to compare the efficiency of Q-Switched Nd: YAG laser and fractional Er: YAG laser. MATERIAL/METHOD: The lesions in both arms were randomly divided into areas A and B. Fractional Er: YAG 2940 nm laser performed to area A 1.5 J/cm2 , spot size 7 mm, frequency 3 Hz and three passes and Q-Switched Nd: YAG 1064 nm laser performed to Area B, 4-6 J/cm2 spot size 4 mm, 8 Hz frequency, and as a single pass. Both lasers were performed in 4 sessions at 3-week intervals. The global improvement scale evaluated treatment responses in dyspigmentation and skin texture. RESULTS: Twenty patients completed the study, and the mean age of a total of 20 patients was 22.9. There was no significant difference in dyspigmentation and skin texture with global improvement scale between Area A and Area B, respectively (p = 0.078, p = 0.638). In addition, there was no significant difference between patient satisfaction levels after treatment in Area A and Area B (p = 0.868). CONCLUSION: The efficiency of the fractional Er: YAG 2940 nm laser was found equal to the Q-switched Nd: YAG 1064 nm laser. Fractional Er: YAG 2940 nm laser may be a new treatment option in the treatment of keratosis pilaris.

Keratosis pilaris and filaggrin loss-of-function mutations in patients with atopic dermatitis - Results of a Finnish cross-sectional study.

Keratosis pilaris (KP) associates with epidermal barrier defects in atopic dermatitis (AD) but its role in disease severity and concomitant atopic diseases seems to vary between populations. We performed a cross-sectional observational study with 502 randomly selected AD patients of a Finnish tertiary health care center. At a single clinical examination, disease severity (Rajka Langeland severity score and EASI), clinical signs and patient history were evaluated and total IgE levels and frequent filaggrin (FLG) loss-of-function mutations were investigated. There was no link with disease severity (p = 0.649, 95% CI 0.569-0.654), asthma (p = 0.230, 95% CI 0.206-0.281) or atopic sensitization (p = 0.351, 95% CI 0.309-0.392). Keratosis pilaris was significantly associated with palmar hyperlinearity (p < 0.000, 95% CI 0.000-0.006, OR 4.664, 95% CI 2.072-10.496) and the filaggrin loss-of-function mutation 2282del4 (p < 0.000, 95% CI 0.000-0.009, OR 4.917, 95%CI 1.961-12.330). The prevalence of KP in the cohort was generally low and KP seems to be infrequent in Finnish AD patients. This may be explained by the fact that the tested FLG loss-of-function mutations are rarer in the Finnish population compared for example, with central Europe or Asia. Mutations in other locations of the FLG gene or other genes of the epidermal barrier may play a more important role.

Prominent Follicular Keratosis in Multiple Intestinal Atresia with Combined Immune Deficiency Caused by a TTC7A Homozygous Mutation.

Multiple intestinal atresia with combined immune deficiency (MIA-CID) is an autosomal recessive syndrome due to mutations in the TTC7A gene implicated in the polarization of intestinal and thymic epithelial cells. MIA-CID is lethal in the first year of life in the majority of patients. Dermatological manifestations have been reported in a few cases. We describe a child affected with MIA-CID due to a previously unreported TTC7A homozygous missense mutation. Surgery for bowel occlusion was performed in the first days of life. The patient was totally dependent on parenteral nutrition since birth and presented severe diarrhea and recurrent infections. He underwent hematopoietic stem cell transplantation at 17 months with complete donor engraftment and partial immunity improvement. In the second year of life, he progressively developed diffuse papular follicular keratoses on ichthyosiform skin, nail clubbing, and subungual hyperkeratosis. Histopathology showed hyperkeratosis with follicular plugging and scattered apoptotic keratinocytes, visualized at an ultrastructural examination. Our findings expand the spectrum of dermatological manifestations which can develop in MIA-CID patients. Examination of further patients will allow defining whether keratinocyte apoptosis is also a disease feature.

Treatment of keratosis pilaris rubra with 577-nm pro-yellow laser.

OBJECTIVE: Keratosis pilaris rubra (KPR) is a rare group of idiopathic hereditary disorders of keratinization, and it is considered as variants of keratosis pilaris. It is characterized by a well-defined erythema and small, keratotic follicular papules that are seen on the cheeks and preauricular area. Keratosis pilaris rubra is an aesthetically distressed situation, and especially vascular erythema is the most common complaint. In recent years, pro-yellow (577 nm) laser, laser system with yellow light wavelength, has been used as an alternative for seeking more effective treatment especially in vascular lesions. However, in the literature, pro-yellow laser therapy has never been used before in keratosis pilaris rubra. Therefore, we wanted to evaluate the effectiveness of the pro-yellow laser in keratosis pilaris rubra patients. MATERIALS AND METHODS: In our study, four patients with keratosis pilaris rubra treated with pro-yellow laser in our Cosmetology Unit between December 2017 and March 2019 were evaluated. The first session was started with 20 j/cm2 and the dose increased 2 j/cm2 at each session. The dose was increased up to 26 j/cm2 , a total of four sessions (20-22-24-26 j/cm2 ) was applied in treatment. All the sessions were used in treatment scanner mode. RESULTS: Objectifying a clearance of erythema >75% was clinically evident in three patients, in the fourth patient, erythema regressed approximately 50%. There has been no recurrence of the lesions after a minimum three months follow-up. There was no permanent side effect in any patient. CONCLUSION: Pro-yellow laser is a well option for the treatment of keratosis pilaris rubra, and we think that it could be a safety choice therapy. In addition, a well tolerance to treatment and a low incidence of serious side effects make it a very reliable therapy. Further clinical studies are needed to improve our findings.

Keratosis follicularis spinulosa decalvans-like cicatricial alopecia in a patient with cardiofaciocutaneous syndrome.

We describe a patient with the keratosis pilaris atrophicans variant of cicatricial alopecia in conjunction with cardiofaciocutaneous syndrome.

Keratosis pilaris rubra successfully treated with topical sirolimus: Report of a case and review of the literature.

Keratosis pilaris rubra (KPR) is a subtype of keratosis pilaris (KP) presenting with numerous "grainlike" follicular papules in a background of confluent erythema most often affecting the face and upper extremities with persistence beyond puberty. Treatment has remained challenging with inconsistent benefit from topical therapies such as emollients, keratolytics, corticosteroids, and retinoids, though case reports documenting success with pulsed dye laser therapy have been found. We present a case of KPR in a 15-year-old boy who was successfully treated with topical sirolimus 1% cream.

Follicular keratosis of the face in pediatric patients of color.

BACKGROUND/OBJECTIVES: Follicular keratosis (FK) is a poorly understood disorder presenting with multiple, grouped hyperkeratotic follicular papules typically affecting the chin or jawline. This study describes the clinical presentation, histopathology, management, and outcomes of a series of pediatric patients of color with FK of the face, thought to be related to rubbing or friction on the skin. METHODS: Retrospective review of 20 pediatric patients with FK of the face who presented to our pediatric dermatology practice between April 2019 and October 2021. RESULTS: Twenty patients (mean age 12.1 years, 13 females), all self-identified as Black/African American, were included. All presented with an initially asymptomatic, hyperpigmented patch containing multiple hyperkeratotic follicular papules, located on the cheek, chin, upper lip, and/or jawline. Five patients endorsed a history of rubbing the site. Nine patients had onset of the lesions during the COVID-19 pandemic. Treatments included topical vitamin D analogs, corticosteroids, and/or retinoids. Topical vitamin D analogs and retinoids improved the texture and hyperpigmentation of the follicular lesions in only four patients, while topical corticosteroids had no effect. Histopathological examination of two patients revealed multiple dilated follicles containing keratinized material and associated with a sparse dermal inflammatory infiltrate in one patient and granulomatous inflammation within the dermis in the other. CONCLUSIONS: In our cohort of pediatric patients with FK, patients of color were preferentially affected, and all cases were associated with hyperpigmentation. Some patients presented during the COVID-19 pandemic suggesting that friction from facial mask wearing may have induced or exacerbated this uncommon condition.

Keratosis pilaris in collagen type VI-related disorders.

Keratosis pilaris is a common skin condition associated with a number of syndromes, including collagen type VI-related disorders. Our patient, recently diagnosed with Ullrich congenital muscular dystrophy, presented with severe keratosis pilaris, hypotonia, and velvety skin on the palms and soles. We present this case to highlight the importance of including cutaneous findings, such as keratosis pilaris, to aid in the diagnosis when evaluating patients with syndromic features.

Colonic Chicken Skin Mucosa Surrounding Colon Polyps Is an Endoscopic Predictive Marker for Colonic Neoplastic Polyps.

Background/Aims: Narrow band imaging provides an accurate diagnosis of colonic polyps. However, these diagnostic modalities are not used as standard endoscopic tools in most institutions. This study aims to investigate whether the chicken skin mucosa (CSM) surrounding the colon polyp yields additional information about colorectal polyps, including histological differentiation of neoplastic and non-neoplastic polyps, under conventional white light colonoscopy. Methods: This study prospectively observed 173 patients who underwent endoscopic polypectomy and reviewed the clinical data and pathologic reports of 313 polyps from a university hospital. Two endoscopists each performed colonoscopy and polypectomy and assessed the CSM. The association between CSM surrounding colorectal polyps and histology was analyzed. Results: The majority (91.3%) of CSM-positive polyps were neoplastic (sensitivity, 37.90%; specificity, 86.15%; p<0.001). In logistic regression, the neoplastic polyps were associated with positive CSM (adjusted odds ratio [OR], 3.51; 95% confidence interval [CI], 1.45 to 9.25; p=0.007), protruded polyps (adjusted OR, 4.85; 95% CI, 1.65 to 17.23; p=0.008), and neoplastic histology-associated pit pattern (pit III, IV, and V) (adjusted OR, 10.14; 95% CI, 4.85 to 22.12; p=0.000). Furthermore, advanced adenomas were associated with positive CSM (adjusted OR, 5.64; 95% CI, 1.77 to 20.28; p=0.005), protruded polyps (adjusted OR, 3.30; 95% CI, 1.15 to 9.74; p= 0.026), and ≥10 cm polyp size (adjusted OR, 18.56; 95% CI, 3.89 to 147.01; p=0.001). Conclusions: Neoplastic and advanced polyps were associated with CSM-positive polyps. These findings suggest that CSM is a useful marker in differentiating neoplastic polyps and advanced polyps under conventional white colonoscopy.

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.

A detailed regimen of isotretinoin for the successful treatment of severe keratosis pilaris.

Although a well-known recommended treatment option, there are currently no studies that describe the detailed regimen of isotretinoin for the treatment of primary keratosis pilaris. Based on previous studies involving other hyperkeratotic disorders, this report describes a safe and effective treatment course of isotretinoin for severe keratosis pilaris.

Atypical keratosis pilaris-like lesions in a patient with Bethlem myopathy.

Bethlem myopathy is a collagen VI-related myopathy. Collagen VI is primarily not only associated with the extracellular matrix of skeletal muscle, but is also found in the skin, blood vessels, and other organs. Dermatologic findings described for Bethlem myopathy include follicular hyperkeratosis and abnormal scar formation, although clinical and histopathologic photographs remain elusive in the literature. We present a case of atypical keratosis pilaris-like follicular lesions in a patient with Bethlem myopathy and provide histopathologic correlation to better characterize the development of skin lesions in this rare neuromuscular disease.

Uleritema ofriógenes como entidad asociada al síndrome 18p- en un paciente pediátrico / Ulerythema ophryogenes as an entity associated with 18p- syndrome in a pediatric patient

El uleritema ofriógenes es un trastorno cutáneo benigno y poco frecuente que se presenta habitualmente en la infancia. Se caracteriza por pápulas foliculares eritematosas y queratósicas en el lateral de las cejas, que con el tiempo suelen evolucionar a alopecia cicatricial. Dicha entidad puede aparecer como manifestación clínica aislada o asociada a varios síndromes congénitos (18p-, Cornelia de Lange, Noonan y Rubinstein- Taybi, entre otros). Presentamos el caso de un paciente de 13 años con síndrome 18p- que consultó por lesiones puntiformes rugosas al tacto y pérdida de pelo en ambas cejas (uleritema ofriógenes), así como por hiperqueratosis pilar en brazos. Esta tríada, conocida como síndrome de Zouboulis, ha sido poco descrita en la literatura. Se considera que el reconocimiento del uleritema ofriógenes es de crucial importancia ya que, ante su presencia, debería realizarse una anamnesis y una exploración física exhaustivas en búsqueda de otras alteraciones que pudieran orientar a la existencia de un trastorno genético subyacente.

Ulerythema ophryogenes is a benign and rare skin disorder commonly presenting in childhood. It is characterized by erythematous and keratotic follicular papules located on the side of the eyebrows, and which over time tends to evolve into scarred alopecia. This entity may appear as an isolated clinical manifestation or associated with several congenital syndromes (18p-, Cornelia de Lange, Noonan, Rubinstein-Taybi, among others). We present a 13-year-old male with 18p- syndrome who consults for rough lesions and hair loss in both eyebrows (ulerythema ophryogenes), as well as for hyperkeatosis pilaris in both arms. This triad, known as Zouboulis syndrome, has been rarely reported in the literature. We consider that the recognition of ulerythema ophryogenes is of crucial importance since, in view of its presence, comprehensive anamnesis and physical examination should be performed in search of other alterations that could guide the existence of an underlying genetic disord