Rubra Pilaris Research Articles

Dermatological manifestations, management, and care in rasopathies.

RASopathies are rare genetic disorders caused by germline pathogenic variants in genes belonging to the RAS/MAPK pathway, which signals cell proliferation, differentiation, survival and death. The dysfunction of such signaling pathway causes syndromes with overlapping clinical manifestations. Skin and adnexal lesions are the cardinal clinical signs of RASopathies, such as cardiofaciocutaneous syndrome, Noonan syndrome with multiple lentigines, formerly known as LEOPARD syndrome, Costello syndrome, neurofibromatosis (NF1), Legius syndrome, Noonan-like syndrome with loose anagen hair (NSLH) and Noonan syndrome. As NF1, one of the most common RASopathies, described in 1882, has its clinical features well delineated, we will focus on the dermatological diagnosis, management and care of non-NF1 RASopathies, which are less known and more recently described. Dermatological manifestations are important clinical diagnostic elements that can aid differential diagnosis among RASopathies. They can affect dermis and epidermis, causing pigmented lesions (melanocytic nevi, café-au-lait spots, and lentigines), hyperkeratosis (keratosis pilaris, ulerythema ophryogenes, and palmoplantar keratosis) or hyperplasia. To date there are rare known links to malignancy, but oftentimes skin lesions require close attention because they can highly affect quality of life.

Keratosis pilaris atrophicans faciei: An observational, descriptive, retrospective clinical study.

Keratosis pilaris atrophicans faciei (KPAF) is a hereditary follicular disorder, an atrophicans subtype of keratosis pilaris (KP) with a highly elusive diagnosis. Clinically, it presents with follicular, horny papules surrounded by an erythematous halo of the cheeks, forehead, chin and eyebrows, and it is followed by a gradual hair loss on the lateral margins of the eyebrows. The onset is as early as a few months after birth, but it is mainly diagnosed in children and adolescents and it can persist through adulthood. At present, the natural progression of the disease is poorly understood, which makes a correct diagnosis highly unlikely. The aim of the present study was to describe the clinical characteristics of KPAF in patients encountered in daily practice, in order to find common characteristics that may aid in the earlier recognition of the disease. An observational, descriptive, retrospective study was performed on 14 patients diagnosed with KPAF between January 2000 and December 2020. The mean age at diagnosis was 17.04 years and the onset of clinical symptoms appeared at a mean age of 4.85 years. The first clinical symptom was KP involving either the upper or lower limbs, or both. Then, erythema of the face appeared at a mean age of 7.21 years, keratotic papules on the face at a mean age of 8.35 years and, finally, loss of hair on the lateral margins of the eyebrows at a mean age of 14 years. The patients also had concomitant xerosis cutis, multiple mole syndrome, acne, contact dermatitis and Laugier-Hunziker syndrome. Evidence of disease progression, associations, as well as efficacious treatment measures are lacking. An earlier diagnosis potentially allows for a more efficacious, targeted treatment option. Either topical emollients, systemic retinoids or laser therapy may prove effective for each patient individually.

Nail Patterns in Papulosquamous Disorders- An Observational Study from Southern India

Introduction: Nail changes are always a cause of physical handicap and psychological stress in this era where utmost importance is given to cosmetic appearance. Other than trauma and infections, Papulosquamous disorders are major contributor to nail changes. Thorough knowledge of their patterns will aid in early detection and treatment before irreversible damage to nails occurs. Aim: To observe the clinical patterns of nail changes in various papulosquamous disorders. Materials and Methods: This observational descriptive cross- sectional study was conducted in a tertiary care set up at Government Coimbatore Medical College, Coimbatore from June 2016 to June 2017. The study group comprised of 104 cases of various papulosquamous disorders. The type of papulosquamous disorder, presence of nail changes, their onset, duration, various patterns and associated co-morbidities were noted in detail. The observed data were entered in Microsoft Excel and data analysis was done in Epi Info system. Results: Out of the 104 cases taken for study 71 (68%) had nail changes. Majority of them were in 31-45 years age group (n=29; 41%). More of males (n=38, 54%) had nail changes than the females (n=33, 46%). Psoriasis (n=47; 66%) was the most common papulosquamous disorder with nail changes followed by lichen planus (n=9; 13%) and pityriasis rubrapilaris (n=7; 10%). Pitting of nails was the most common nail pattern (n=44; 62%), followed by subungual hyperkeratosis (n=24; 34%), thickened nail plate and longitudinal striations (both n=19; 27%). Finger nails were more affected than toe nails. Psoriasis and pityriasis rubrapilaris had 100% nail involvement. The patterns of nail changes were maximum in psoriasis and lichen planus. Beaus lines was observed in most of the papulosquamous disorders except Lichen nitidus and Lichen striatus. The time gap for onset of nail changes was longer for psoriasis (4.2 years) and shorter for pityriasis rosea (two months). In lichen striatus and lichen nitidus, nails were involved only in children. Minimal nail changes were observed in para psoriasis and pityriasis lichenoides. More number of co-morbidities like diabetes, hypertension, atopy and arthritis were seen in psoriasis. Conclusion: In the present study, it was observed that the nail changes were more common in psoriasis, lichen planus and pityriasis rubra pilaris among the papulosquamous disorders. The highly frequent nail patterns were pitting and subungual hyperkeratosis.

Keratosis pilaris

Keratosis pilaris is characterized by small bumps around hair follicles. Keratosis pilaris simplex results in gray and keratotic papules mainly on the arms, thighs and buttocks. It mainly affects women. Keratosis pilaris rubra often results in keratosis pilaris atrophicans. Common variants of keratosis pilaris include: ulerythema ophryogenes, atrophoderma vermiculata, Siemens alopecia. Keratosis pilaris is a genetic disorder and can occur in association with other hereditary diseases such as Noonan syndrome or vitamin disorders. Treatment is mainly based on emollients and keratolytics, but they have only a suspensive effect. We report the case of a 30 year old woman with a personal and family history of atopy, presenting with diffuse keratotic papules on the trunk. The remainder of the physical examination revealed no genetic abnormality. Treatment was based on emollients and keratolytics with slight improvement.

Dermatological manifestations in cardiofaciocutaneous syndrome: a prospective multicentric study of 45 mutation-positive patients.

Data on dermatological manifestations of cardiofaciocutaneous syndrome (CFCS) remain heterogeneous and almost without expert dermatological classification. To describe the dermatological manifestations of CFCS; to compare them with the literature findings; to assess those discriminating CFCS from other RASopathies, including Noonan syndrome (NS) and Costello syndrome (CS); and to test for dermatological phenotype-genotype correlations. We performed a 4-year, large, prospective, multicentric, collaborative dermatological and genetic study. Forty-five patients were enrolled. Hair abnormalities were ubiquitous, including scarcity or absence of eyebrows and wavy or curly hair in 73% and 69% of patients, respectively. Keratosis pilaris (KP), ulerythema ophryogenes (UO), palmoplantar hyperkeratosis (PPHK) and multiple melanocytic naevi (MMN; over 50 naevi) were noted in 82%, 44%, 27% and 29% of patients, respectively. Scarcity or absence of eyebrows, association of UO and PPHK, diffuse KP and MMN best differentiated CFCS from NS and CS. Oral acitretin may be highly beneficial for therapeutic management of PPHK, whereas treatment of UO by topical sirolimus 1% failed. No significant dermatological phenotype-genotype correlation was determined. A thorough knowledge of CFCS skin manifestations would help in making a positive diagnosis and differentiating CFCS from CS and NS.

Frontal fibrosing alopecia and ulerythema ophryogenes as two entites that can transist one into another

Frontal fibrosing alopecia and ulerythema ophryogenes as two entites that can transist one into another

Overlap Between Ulerythema Ophryogenes and Keratosis Follicularis Spinulosa Decalvans: a Case Report

Abstract Ulerythema ophryogenes and keratosis follicularis spinulosa decalvans are rare folliculocentric keratotic disorders, from the group of follicular genokeratoses, characterized by keratosis pilaris atrophicans: follicular keratotic papules, sometimes with surrounding erythema, which eventually result in fibrosis, atrophy, progressive scarring and permanent hair loss. Ulerythema ophryogenes begins at birth or soon thereafter; it involves the lateral eyebrows, spreads medially and eventually affects the entire eyebrows, cheeks, and less frequently, forehead and asjecebt scalp. Involvement of the scalp has apparently not been reported in cases in which the eyebrows were predominantly involved. In addition to sporadic cases, ulerythema ophryogenes has been reported among relatives. Keratosis follicularis spinulosa decalvans is also a genetically heterogeneous syndrome which begins in infancy or childhood by involving hair bearing skin, especially the scalp; rarely it is confined to the face involving only eyebrows and eyelashes, but affects predominantly the scalp, leading to severe progressive cicatricial alopecia. Both conditions tend to progress until puberty. The authors present a case of an otherwise healthy 19-year-old male patient, with absence of lateral eyebrows since childhood, which spread symmetrically and medially, until puberty affecting the entire eyebrows, whereas the eyelashes were completely spared. On examination, skin findings on the face, trunk and extremities pointed to ulerythema ophryogenes: apart from hair loss, the lateral eyebrows were highly erythematous; a great number of disseminated follicular, slightly keratotic papules (keratosis pilaris) pin- or match-head sized, were seen on the trunk, extensor surface of the arms and legs, as well as the buttock, and on palpation the skin felt like a “nutmeg grater”. However, follicle-based erythematous papules (focal patchy alopecia) were found not only along the eyebrows but also partly in the parietal capillitium forming focal patchy alopecia, which is a finding characteristic for keratosis follicularis spinulosa decalvans; the histopathological analysis of the biopsy specimens taken from the parietal capillitium has confirmed the clinical diagnosis. Cytogenetic analysis showed no karyotypic abnormalities. Family history showed that the patient’s mother and maternal grandfather also suffered from hair loss especially of the lateral eyebrows. This paper presents an overlap between two rare follicular genokeratoses in a young male with a positive family history, who presented with ulerythema ophryogenes involving not only the eyebrows, but also the scalp, in the form of parietal, focal cicatricial patchy alopecia.

Role of Diet in Dermatological Conditions

In recent years nutritional deficiency diseases have been reported in developed countries. Nutritional deficiencies can be due to inadequate intake, abnormal absorption or improper utilisation. Many nutrients are essential for life, an adequate amount of nutrients in the diet is necessary for providing energy, building and maintaining body organs and for various metabolic process. Skin disorders have long been associated with nutritional deficiencies. Nutrition is one of the most important parameters that are involved in modulating skin health and condition. Nutritional status plays an important role in maintenance of healthy skin. A variety of nutritive factors such as small peptides minerals, vitamins, macronutrients and micronutrients work together to maintain the barrier functions of skin in the face of everyday challenges. Changes in nutritional status that alters skin structure and function can also directly affect skin appearence. In general dermatological problems were diet plays a role are atopic eczema, urticaria, dermatitis herpetiformis, psoriasis, pityriasis, rubra pilaris, purpura, scurvy, refsumes disease, ichthyosis, vitiligo, hypo pigmentary conditions, acne, rosacea, kwashiorkor, marsmus, stomatitis, phrynoderma, pellagra, acro dermatitis enteropathica, homocysteinuria, hartnup disease, gout, porphyrias, xanthomas, hyper carotenemia and lycopenemia. Dietary changes or modification might help to prevent recurrences of many skin diseases.

Red face and fungi infection

Red face syndrome is characterized by an erythematous dermatitis that is produced by different entities. These include rosacea, seborrheic dermatitis, contact dermatitis, atopic dermatitis, psoriasis, cutaneous lupus, photodermatosis, post-topical steroid dermatosis, demodicosis, borderline borderline (BB) leprosy, mastocytosis, carcinoid, postneoplasia flushing, cutaneous lymphoma, tineas, ulerythema ophryogenes, and psychosomatic flushing. Red face is a relatively common dermatologic manifestation. Our goal is to review tinea corporis and other fungi that affect this region causing facial erythema and its therapeutic management.

Red face revisited: Disorders of hair growth and the pilosebaceous unit

This paper reviews the recent literature on the diseases of the hair and pilosebaceous unit that may cause a red face. We discuss the epidemiology, clinicals, pathogenesis, and therapy of lichen planopilaris with its variants, discoid lupus erythematosus, folliculitis decalvans, dissecting folliculitis, acne keloidalis nuchae, pseudofolliculitis barbae, tinea capitis, tinea barbae, folliculitis of diverse causative factors and inflammatory follicular keratotic syndromes, ulerythema ophryogenes, atrophoderma vermiculatum, keratosis follicularis spinulosa decalvans, and folliculitis spinulosa decalvans.

Ulerythema Ophryogenes, A Rarely Reported Cutaneous Manifestation of Noonan Syndrome: Case Report and Review of the Literature

Ulerythema ophryogenes (also known as keratosis pilaris atrophicans faciei) is a rarely reported cutaneous manifestation of Noonan syndrome. Recognizing ulerythema ophryogenes as a cutaneous association in Noonan syndrome may aid in the diagnosis of this relatively common genetic condition. We present a case of a patient with Noonan syndrome and ulerythema ophryogenes associated with a SOS1 mutation and review the literature on this association. To the best of our knowledge, this is the second case of Noonan syndrome proven to be due to an SOS1 mutation in which ulerythema ophryogenes was clinically recognized and specifically diagnosed. The presence of ulerythema ophryogenes in a patient with Noonan syndrome increases the likelihood of a SOS1 mutation. Further reports by dermatologists and medical geneticists documenting ulerythema ophryogenes and not just descriptions of sparse or absent eyebrows will help support this genotype-phenotype correlation.

Dermatological phenotype in Costello syndrome: consequences of Ras dysregulation in development

The RASopathies are a class of human genetic syndromes caused by germline mutations in genes that encode protein components of the Ras/mitogen-activated protein kinase (MAPK) pathway. Costello syndrome (CS) is a RASopathy caused by mutations in the HRAS gene, a key regulator of signal transduction. To quantify the specific cutaneous phenotype observed in 46 individuals with Costello syndrome with confirmed HRAS mutations. This was a cross-sectional study. Dermatological surveys were designed by the authors and were completed by parents of mutation-positive individuals with CS at the Costello Syndrome Family Network (CSFN) conferences in 2007 and 2009. Dermatological examinations were performed by the authors at the CSFN conferences. Cutaneous papillomas were reported in 33 of the 46 (72%) participants, with age of onset ranging from infancy to 22years. Individuals with CS are more likely than patients with cardiofaciocutaneous syndrome (CFC) to present with cutaneous papillomas (72% vs. 5%, P<0·001) and palmoplantar keratoderma (76% vs. 36%, P<0·001). Individuals with CS are less likely than individuals with CFC to present with sparse or absent eyebrows (9% vs. 90%, P<0·001) or keratosis pilaris (33% vs. 80%, P=0·001). This study also identified that loose, redundant skin on the hands and feet, 'stippled' dermatoglyphs (pachydermatoglyphia) on the fingertips (eight of 26, 31%) and acanthosis nigricans (17 of 46, 37%) are frequent features of CS. While there is significant phenotypic overlap among syndromes of the Ras/MAPK pathway, individuals with CS are more likely than individuals with CFC syndrome to present with cutaneous papillomas, palmoplantar keratoderma and full eyebrows, and are less likely to present with ulerythema ophryogenes, keratosis pilaris or multiple naevi. The dermatological features of CS, a Ras dysregulation syndrome, share many features with cutaneous paraneoplastic syndromes. This may provide further insight into the role of Ras signalling in cutaneous paraneoplastic syndromes.

Keratosis pilaris rubra and keratosis pilaris atrophicans faciei treated with pulsed dye laser: report of 10 cases

Keratosis pilaris rubra and keratosis pilaris atrophicans faciei treated with pulsed dye laser: report of 10 cases

Ceratose pilar e ulerythema ophryogenes em mulher com monossomia do braço curto do cromosomo 18

Partial monosomy of the short arm of chromosome 18 (18p- syndrome) is characterized mainly by speech delay, mild to moderate mental retardation and short stature. We describe a patient with the 18p- syndrome and widespread severe keratosis pilaris and ulerythema ophryogenes. This is the fourth case in which such an association has been reported. This association is of considerable interest because it may uncover a candidate genomic region and help to identify the gene responsible for follicular keratinization.

Keratosis pilaris rubra and keratosis pilaris atrophicans faciei treated with pulsed dye laser: report of 10 cases

Keratosis pilaris rubra (KPR) and keratosis pilaris atrophicans faciei (KPAF) are both keratinization disorders characterized by erythema and keratotic follicular papules usually located on cheeks, forehead, chin and eyebrows. Topical keratolytics, vitamin D3 analogues, antibiotics, topical and oral retinoids have been used with limited results. As this condition can be socially very limiting, the need for an effective treatment has led to the use of other technologies such as pulsed dye laser (PDL) or intense pulsed light. The aim of this study was to assess the efficacy and safety of PDL in patients with KPR or KPAF. Ten patients with KPR or KPAF were treated with two to seven sessions of PDL at 595-nm wavelength. Laser therapy was performed using a spot size of 7 or 10mm, a pulse duration of 0.5 or 1.5ms and a fluence from 5 to 9J/cm(2) . Two dermatologists evaluated treatment effectiveness by means of photographs of the patients before starting and after finishing the therapy. Complete resolution of erythema was achieved in three patients; clearance of erythema was >75% in the other seven patients. Transient purpura was present in all patients for about 2weeks and one patient presented postinflammatory hyperpigmentation for 7months. We consider that PDL is a good option for the treatment of KPR and KPAF. A marked reduction in erythema is achieved in all patients with a low incidence of side effects.

Ulerythema Ophryogenes, a Rare and Often Misdiagnosed Syndrome: Analysis of an Idiopathic Case

Keratosis pilaris (KP) is a follicular hyperkeratosis disorder which is frequently detected in the adult population (44%), mostly in female adolescents (80%). It is a genetic autodominant dermatosis with variable penetrance, but no specific gene association has been determined, even though association to the presence of chromosome 18p deletion has been reported in some cases. We report the case of a 51-year-old Caucasian woman affected by keratosis pilaris gradually progressing with age and with a story of multiple abortions. Standard karyotype and CGH array analyses did not reveal any genetic abnormality. Virological analyses detected the presence of HPV 36 DNA inside the dorsum biopsy, leading to hypothesize its involvement in the evolution of the lesion. Clinical history and patient examination led the diagnosis of an idiopathic case of Ulerythema ophryogenes. The analysis of more cases could be useful to verify the involvement of cutaneous HPV in the progression of the clinical manifestation of the KP variants.

Dermatological findings in 61 mutation-positive individuals with cardiofaciocutaneous syndrome

The RASopathies are a class of human genetic syndromes that are caused by germline mutations in genes which encode components of the Ras/mitogen-activated protein kinase (MAPK) pathway. Cardiofaciocutaneous (CFC) syndrome is characterized by distinctive craniofacial features, congenital heart defects, and abnormalities of the skin and hair. Systematically to characterize the spectrum of dermatological findings in mutation-positive individuals with CFC syndrome. Dermatological surveys were designed by the authors and distributed to the study participants through CFC International or directly by the authors (K.A.R. and D.H.S.) between July 2006 and August 2009. A second follow-up survey was collected between December 2007 and August 2009. When available, digital images and medical records of the participants were obtained. Study participants included individuals with CFC syndrome who have a mutation in BRAF, MAP2K1, MAP2K2 or KRAS. Individuals with CFC syndrome have a variety of dermatological manifestations caused by dysregulation of the MAPK pathway in development. Numerous acquired melanocytic naevi were one of the most striking features: more than 50 naevi were reported by 23% (14/61) of participants and of those, more than 100 naevi were reported by 36% (5/14). Keratosis pilaris was reported in 80% (49/61) of cases. Ulerythema ophryogenes was common, occurring in 90% (55/61). Infantile haemangiomas occurred at a greater frequency, 26% (16/61), as compared with the general population. CFC syndrome has a complex dermatological phenotype with many cutaneous features, some of which allow it to be differentiated from the other Ras/MAPK pathway syndromes. Multiple café-au-lait macules and papillomas were not identified in this CFC cohort, helping to distinguish CFC from other RASopathies such as neurofibromatosis type 1 and Costello syndrome.

Palmoplantar keratoderma, pseudo‐ainhum, and universal atrichia: A new patient and review of the palmoplantar keratoderma‐congenital alopecia syndrome

Palmoplantar keratoderma (PPK) may concur with congenital alopecia (CA) in various genodermatoses. We report on a 10-year-old girl with generalized atrichia and a severe form of PPK causing pseudo-ainhum, sclerodactyly, and contractures, a phenotype not consistent with any well-defined condition. Non-specific additional findings comprised mild nail dystrophy and widespread keratosis pilaris including ulerythema ophryogenes. Direct sequencing of the GJB2 and LOR coding regions yielded normal results. A review identified two additional sporadic and four familial cases with PPK and CA. Comparison between familial cases suggested the existence of two genetically and phenotypically distinct types of PPK-CA: (i) an autosomal dominant form (Stevanović type), a variable and benign phenotype without significant hand complications, and (ii) a more complex autosomal recessive variant (Wallis type) with contractures, sclerodactyly, and pseudo-ainhum. Nuclear cataract may represent an additional although not constant finding in the Wallis type PPK-CA. Further reports are required to test this preliminary conclusion.

Keratosis pilaris and keratosis pilaris atrophicans faciei

Keratosis pilaris and ulerythema ophryogenes (keratosis pilaris atrophicans faciei) are hereditary disorders with altered follicular keratinization that show follicular, horny papules surrounded by an erythematous halo. Ulerythema ophryogenes is an uncommon variant of keratosis pilaris characterized by erythematous follicular papules of the eyebrows and cheeks followed by a gradual loss of hair. On the background of 15-year-old boy who presented with keratosis pilaris and ulerythema ophryogenes, we discuss the various clinical manifestations of keratosis pilaris.

Hereditary woolly hair and keratosis pilaris

We describe a family with woolly hair and ulerythema ophryogenes spanning four generations. Both woolly hair and ulerythema ophryogenes have been associated with Noonan syndrome and cardiofaciocutaneous syndrome (CFC), two disorders with considerable phenotypic overlap. This family did not exhibit any of the other findings characteristic of either Noonan syndrome or CFC, similar to a previously described pedigree with hereditary woolly hair. Woolly hair elicits a broad differential diagnosis, including woolly hair nevus and several genodermatoses. Our report reviews the evaluation of woolly hair and discusses the conditions associated with this physical finding.