Ichthyosis follicularis, alopecia, and photophobia syndrome: a case report and a pathological insight into pilosebaceous anomaly

Ichthyosis follicularis, alopecia, and photophobia (IFAP) syndrome (OMIM 308205) is an extremely rare X-linked oculocutaneous genetic disorder characterized by follicular keratotic papules, total to subtotal alopecia, and photophobia. Previous reports depicted the histopathological features of affected skin lesions, represented by marked follicular plugging and hypoplastic pilosebaceous structures. However, past studies provided limited pathological information of pilosebaceous unit anomaly. Here, we report a 3-year-old boy's case with this uncommon condition. In this case, scalp biopsy samples were processed by both vertical and transverse sectioning techniques, which enabled a more detailed and quantitative pathological analysis of pilosebaceous structures. In vertical slices, miniaturized anagen hair follicles with characteristic follicular plugs were observed. A transverse section identified abortive sebaceous glands in hair follicles, a finding rarely observed in vertical sections. In addition, a transverse slice demonstrated that the number of total hair follicles was not significantly decreased compared with the average hair follicle density in Asians, suggesting that the pilosebaceous hypoplasia might arise from impaired maturation, not from initiation defect, during hair follicle morphogenesis. This study provides a more comprehensive pathological insight into pilosebaceous anomaly in IFAP syndrome and substantiats the usefulness of the combination of vertical and transverse sectioning approaches in the pathological examination of congenital hypotrichosis, including IFAP syndrome.     

Selective Decrease of Eumelanin in Hypopigmented Epidermis of Hypomelanosis of Ito

Abstract: A Japanese infant had bilateral hypopigmented macules in a whorled or marble-cakelike configuration on her trunk and extremities. Her irides were bluish gray and her hair was dark brown. She had photophobia and macrocephaly with developmental delay. Analysis of peripheral lymphocytes and dermal fibroblasts disclosed a normal chromosomal pattern. A new finding was that the eumelanin content of the hypopigmented epidermis was decreased. We suggest that at least a portion of patients with this disorder have a defect in eumelanogenesis in hypopigmented skin.     

毛囊性鱼鳞病、秃发、畏光综合征一例及基因检测

【摘要】 患儿男,2岁2月龄,因生后毛发异常就诊。患儿生后头皮未见毛发,周身皮肤粗糙,可见米粒大小毛囊性丘疹,肛周可见红斑。生后15 d左右家长发现其畏光。皮肤科检查：全身弥漫分布米粒大小毛囊性丘疹,头发、睫毛、眉毛均未见生长;肛周可见境界清楚红斑,边缘可见脱屑。基因检测发现,患儿X染色体MBTPS2基因存在c.661T>A变异,该变异导致第221号氨基酸由苯丙氨酸变为异亮氨酸,即p. Phe221Ile。患儿母亲为相同位点的杂合突变。诊断：毛囊性鱼鳞病、秃发、畏光综合征。     

Odonto-onycho-dermal dysplasia

Summary Odonto-onycho-dermal dysplasia is an ectodermal dysplasia (ED) described once previously in two families who exhibited atrophic malar patches, sparse hair, conical teeth, dystrophic nails and hyperkeratosis of the palms and soles. We describe a boy who developed a blistering malar rash soon after birth. When examined at 11 months, and then at 27 months of age, he had persistent atrophic malar plaques that reddened with heat. He also showed nail dystrophy, sparse hair. lingual concavity of the incisors, a bifid maxillary incisor, a five-cusped molar, and hyperhidrosis of the palms and soles. In addition he had chronic tearing, photophobia, blepharitis, and a mild keratitis.
After reviewing EDs with atrophic or scar-like skin changes, we believe this child most resembles the patients with odonlo-onycho-dermal dysplasia, although his eye findings are unique.     

Keratosis follicularis spinulosa decalvans

Keratosis follicularis spinulosa decalvans is a rare, X-linked disorder of keratinization of the hair follicle with inflammation and atrophy associated with corneal dystrophy and other symptoms. A family with several affected members is reported. The unaffected parents were related. A 12-year-old girl and her 5-year-old brother had follicular spiny hyperkeratoses on the trunk and extremities. The girl had thinning of the eyelashes and eyebrows as well as scarring alopecia of the scalp as additional features of the disease. Both the girl and her brother had corneal dystrophy and photophobia. Two sisters aged 8 and 10 years did not show similar skin or eye findings.     

A Novel Mutation in the MBTPS2 Gene Resulting in Ichthyosis Follicularis,Atrichia, and Photophobia Syndrome

Ichthyosis follicularis, atrichia, and photophobia (IFAP) syndrome is a rare genetic disorder caused by mutations in the MBTPS2 gene. It is characterized by ichthyosis and alopecia from birth. Photophobia may be present in infancy or early childhood. Its mode of inheritance is X-linked recessive; thus, it mostly affects male. The disease severity varies, ranging from mild cases limited to the skin to the severe variant involving multiple extracutaneous features. A 7-year-old boy presented with scanty hair on scalp and eyebrows at birth. On physical examination, scaly patches were observed on the whole body and spiky follicular hyperkeratotic papules were observed on the face and trunk. He also suffered from severe photophobia. Histopathological examination of the scalp showed miniaturized hair follicles without perifollicular fibrosis. Genetic analysis revealed a novel mutation in the MBTPS2 gene which was a homozygous missense mutation of c.245T>C leading to an amino-acid substitution from phenylalanine to serine (p.Phe82Ser). We diagnosed this patient with IFAP syndrome. To date, 25 pathogenic MBTPS2 gene mutations have been identified. To our knowledge, c.245T>C is a novel homozygous missense mutation in the MBTPS2 gene, which has not been reported in Human Gene Mutation Database, ClinVar Database, and Leiden Open Variation Database. Previous reports suggested genotype-phenotype correlations in the MBTPS2 gene mutations. Supported by a previous notion that genotype correlates with phenotype, this novel mutation can be a predictive factor for the mild form of IFAP syndrome, restricted to the classic symptom triad.     

Spiney hyperkeratosis with hair shaft alterations, keratitis and deafness

Two males and a female in a family of seven children from consanguineous parents showed a generalized ichthyosiform dermatosis characterised by spiney hyperkeratosis. Bilateral neurosensory deafness affected only the older child, aged 10 who, in addition, was totally blind. His 1–year–old brother developed photophobia and severe corneal ulcers, and his 5–year–old sister suffered from dry eyes due to scarcity of tears. The three patients showed hair defects, with different degrees of alopecia and alterations of the hair–shaft, including eliptical cross–section tike woolly–hair. We stress the clear recessive inheritance of this association, its wide clinical variability and the less known hair shaft alterations.     

角膜炎、鱼鳞病、耳聋综合征一例

患儿女,10岁.出生后1个月头皮、口周、颈部、躯干、臀部及掌跖出现红斑,皮肤干燥粗糙,头发细软、稀疏,易折断.随着年龄增长,红斑基础上出现明显的角化过度和增厚.5岁时出现畏光、视力下降;8岁开始听力逐渐下降.体检:身高109 cm,体重19 kg.皮肤科检查:头发稀少细软,易断;头皮、口周、颈部、躯干、臀部大片棕褐色斑块、结痂;其上可见疣状增生,伴有皲裂、溢脓,有恶臭.四肢皮肤散在黑褐色角化性斑块.掌跖弥漫性角化过度.指(趾)甲增厚,浑浊变白,远端分离、变形.眼科检查:畏光,视力左眼0.5,右眼0.2;双侧球结膜充血,角膜浑浊、角膜血管增生.耳鼻喉科检查:双耳中度感音性耳聋.口腔科检查:牙釉质发育不全,牙间隙明显增宽.GJB2基因检测发现,患儿GJB2基因2号外显子c.C50T杂合突变.诊断:角膜炎、鱼鳞病、耳聋综合征.经口服阿维A治疗,症状明显缓解.     

新发MBTPS2基因突变致毛囊性鱼鳞病、秃发、畏光综合征一例

【摘要】 本文首次报道1例MBTPS2基因c.1165C>T突变致毛囊性鱼鳞病、秃发、畏光综合征。先证者主要临床表现为皮肤干燥、先天性无头发、毛囊角化性丘疹、畏光,伴癫痫,智力、运动发育落后。应用二代测序及一代测序验证显示,先证者和其母亲在MBTPS2基因第9外显子区域存在c.1165C>T（p.pro389Ser）突变。根据患儿临床表现和MBTPS2基因突变遗传学特点,确诊为毛囊性鱼鳞病、秃发、畏光综合征。     

Ichthyosis follicularis with alopecia and photophobia

We treated two unrelated boys with ichthyosis follicularis, a rare skin disorder characterized by extensive noninflammatory spiny follicular hyperkeratoses, severe photophobia, and generalized noncicatricial alopecia. This disorder must be differentiated from keratosis follicularis spinulosa decalvans; ulerythema ophryogenes; keratosis pilaris rubra atrophicans faciei; atrichia with papular lesions; atrophodermia vermiculata; and keratitis, ichthyosis, and deafness syndrome, all of which share some clinical features. Ichthyosis follicularis with alopecia and photophobia appears to be a familial disorder, but too few cases have been reported to establish the exact mode of inheritance.     

Keratitis, ichthyosis and deafness (KID) syndrome

Keratitis, ichthyosis, deafness (KID) syndrome is a genetically determined disorder. The present case is having marked photophobia, bilateral corneal ulceration with vascularisation, neurosensory deafness and skin changes.     

Electron paramagnetic resonance (EPR) spectroscopy for investigating murine telogen skin after spontaneous or depilation-induced hair growth

BACKGROUND: Depilation has greatly promoted our understanding of hair follicle biology, however, only marginally of telogen (the "resting" stage of the hair cycle). Since electron paramagnetic resonance (EPR) spectroscopy provides an instructive technique for analyzing hair biology, it may be useful for telogen research. OBJECTIVES: To identify differences in murine telogen skin after a spontaneous and depilation-induced hair follicle cycling, and to analyze applicability of EPR to investigate telogen. METHODS: Spontaneous or depilation-induced hair cycling in C57BL/6 mice. EPR spectroscopy of unshaven skin and of shaved hair shafts, microscopical examination of plucked or shed hair shafts, standardized histomorphometry. RESULTS: Melanin EPR signals did not differ qualitatively between the two examined types of skin, nor did depilation change the hair length. However, unmanipulated telogen skin revealed greater thickness, stronger EPR signals, 25% more hair shafts, and lower melanin content of individual hair shafts, as creating a much more intricate mosaic of telogen hair follicles with various numbers of hair shafts (0-3) than the skin after depilation-induced hair growth. In both types of skin empty pilary canals were found. Both groups of animals lost hair shafts which were typical of exogen (the actively controlled process of hair shedding). CONCLUSIONS: EPR spectroscopy can be profitably employed to study telogen. Murine telogen skin reveals a kenogen-like phenomenon (the "lag" phase following telogen and exogen when hair follicles remain empty, i.e. are devoid of hair shafts). Murine skin thickness in telogen and individual hair shaft pigmentation depend on the way of hair growth induction. Telogens after a spontaneous or depilation-induced hair growth are biologically distinct.     

Getting under the skin of hair aging: the impact of the hair follicle environment

Like the skin, our hair shows striking changes with age, producing hairs with altered diameter, lustre and texture. The biology of hair aging has focused predominately on various aspects of the hair cycle, follicle size and the fibre produced, but surprisingly the impact of the aging scalp dermal environment on the hair follicle and fibre has been generally overlooked. Hair loss affects both sexes with incidence increasing with age. In men, male pattern-balding (androgenetic alopecia) is driven by androgens and follows a specific pattern of frontotemporal and vertex regression. Women also experience female pattern hair loss (FPHL), presenting as more general, diffuse hair thinning. Hair thinning in women is commonly associated with the menopause, corresponding with other age-related changes in skin. The rapidly growing hair follicle undergoes continued renewal throughout the life span of an individual, where it is exposed to a substantial number of extrinsic and intrinsic stressors. As the hair follicle sits deep within the dermis with its bulb residing in the hypodermis, detrimental age-related changes in the surrounding scalp skin may likely disrupt the hair follicle machinery. The impacts of these changes are unknown, but evidence suggests that scalp skin aging and hair follicle aging go hand-in-hand. Herein, we summarize the evidence that the age-related changes observed in sun-exposed human skin also occur in scalp skin and that these changes are likely to play a contributing role in the aging hair phenotype.     

Contact dermatitis to hair dyes in a Danish adult population: an interview-based study

BACKGROUND: Contact allergy to hair dye ingredients is a well-known entity seen both in consumers using hair dyes and among hairdressers with occupational contact dermatitis. Surveys show that consumers with even severe adverse skin reactions to hair dyes only rarely contact the healthcare services. The frequency of hair dye-induced skin reactions in the consumer population is unknown. OBJECTIVES: An epidemiological investigation with the aim of establishing the proportion of hair dye-induced skin reactions was performed in a population-based sample. METHODS: A representative random sample (n = 4000) was taken of the Danish adult population. Personal interview questions were asked regarding adverse skin reactions to hair dyes, either compatible with a classical allergic eczematous reaction with redness, scaling and itching or a severe allergic reaction with oedema of the forehead and face. The response rate was 65.2%. RESULTS: A total of 18.4% of the male respondents and 74.9% of the female respondents had at some point dyed their hair. The median age at first hair dyeing was 16 years (range 1-80). Adverse skin reactions to hair dyes compatible with an allergic reaction were reported in 5.3% of individuals who had ever used hair dye. Of these, only 15.6% had been in contact with healthcare services after the hair dye reaction. Having had a temporary tattoo was not a significant risk factor for an adverse reaction to hair dyes. CONCLUSIONS: The rate of adverse allergic skin reactions to hair dyes was higher than expected from patch-test studies. Only by studying the clinical types of adverse reactions to hair dyes will it be possible to gather a complete epidemiological picture of the nature and extent of the problems related to hair dye ingredients.     

Familial keratosis follicularis spinulosa decalvans associated with woolly hair

Keratosis follicularis spinulosa decalvans (KFSD) is a rare inherited disorder of keratinization clinically characterized by diffuse follicular hyperkeratosis, progressive scarring alopecia of scalp, eyebrows and eyelashes, corneal dystrophy and photophobia. Woolly hair is a hereditary condition, transmitted as an autosomal dominant or recessive trait, usually seen in Caucasians at birth or shortly after, in which there are curly, thick, often heavily pigmented hairs. We report two cases, a son and his mother, in whom KFSD occurred in association with woolly hair. In addition, various dental anomalies, including agenesis, inclusions and teeth malformations, were present in the child. Interestingly, both patients simultaneously developed an inflammatory tinea capitis caused by Microsporum canis. To our knowledge, the association of KFSD with woolly hair has not been described. The dental anomalies found in the child are intriguing, as they have never been reported previously in patients with KFSD. Finally, the concomitant onset of inflammatory tinea capitis in both patients may be explained by the enhanced susceptibility to fungal infection in keratinizing disorders.     

Ichthyosis follicularis with congenital atrichia, nail dystrophy and palmoplantar keratoderma. Variant of IFAP syndrome or a new entity?

A 23-year-old man was seen for dry, rough skin and alopecia present since birth. There was no history of impaired sweating, photophobia, or lacrimation. Examination revealed generalized cutaneous thorn-like projections with nonscarring alopecia, twenty-nail dystrophy, and palmoplantar keratoderma.     

Ichthyosis follicularis with alopecia and photophobia in a mother and daughter

A mother and daughter having ichthyosis follicularis with alopecia and photophobia (IFAP) are reported, with histopathological and electron microscopic findings. We have followed the clinical course of the mother for 26 years since she was 5 years old, and the daughter since birth. They have had almost all the classical and some of the minor symptoms of IFAP, including severe photophobia, extensive non-inflammatory follicular hyperkeratosis, generalized non-scarring alopecia, hyperkeratosis of the extensor aspect of the four extremities, nail deformity and recurrent cheilitis. In addition, their facial appearance greatly resembles that of previously reported patients. A consistent feature in the mother was florid keratotic inflammatory eruptions on the genital region during each of her pregnancies, which rapidly improved after the delivery. Skin biopsy of the genital lesion showed marked acanthosis with dyskeratosis and spongiotic changes. The electron microscopic examination of diseased skin showed damaged desmosomes with spongiosis. No obvious changes were found in normal appearing skin.     

Potent skin sensitizers in oxidative hair dye products on the Swedish market

Background: In recent years, the alarming increase in contact allergy to hair dyes has drawn much attention. It has been shown that many of the currently allowed hair dye substances are potent skin sensitizers.
Objectives: To study the prevalence of hair dye substances, categorized as potent skin sensitizer, in oxidative hair dye products on the Swedish market.
Materials and Methods: Ingredient labels of 122 oxidative hair dye products from 20 brands were examined. All ingredients were recorded, and the prevalence of hair dye substances categorized as potent skin sensitizers was assessed.
Results: According to ingredient labelling, 120 out of 122 examined oxidative hair dye products contained hair dye substances categorized as potent skin sensitizers. More than 80% of the products contained at least four such substances; 37 hair dye substances categorized as potent skin sensitizers were identified, and 10 of these were more prevalent than p-phenylenediamine.
Conclusions: Hair dye substances categorized as potent skin sensitizers are very common in oxidative hair dye products. A substantial number of potent skin sensitizers are more frequently used than p-phenylenediamine, while only a few are commercially available as patch test substances.     

Plasticity of hair follicle dermal cells in wound healing and induction

The capacity of adult hair follicle dermal cells to participate in new follicle induction and regeneration, and to elicit responses from diverse epithelial partners, demonstrates a level of developmental promiscuity and influence far exceeding that of interfollicular fibroblasts. We have recently suggested that adult follicle dermal cells have extensive stem or progenitor cell activities, including an important role in skin dermal wound healing. Given that up to now tissue engineered skin equivalents have several deficiencies, including the absence of hair follicles, we investigated the capacity of follicle dermal cells to be incorporated into skin wounds; to form hair follicles in wound environments; and to create a hair follicle-derived skin equivalent. In our study, we implanted rat follicle dermal cells labelled with a vital dye into ear and body skin wounds. We found that they were incorporated into the new dermis in a manner similar to skin fibroblasts, but that lower follicle dermal sheath also assimilated into hair follicles. Using different combinations of follicle dermal cells and outer root sheath epithelial cells in punch biopsy wounds, we showed that new hair follicles were formed only with the inclusion of intact dermal papillae. Finally by combining follicle dermal sheath and outer root sheath cells in organotypic chambers, we created a skin equivalent with characteristic dermal and epidermal architecture and a normal basement membrane - the first skin to be produced entirely from hair follicle cells. These data support the hypothesis that follicle dermal cells may be important in wound healing and demonstrate their potential usefulness in human skin equivalents and skin substitutes. While we have made progress towards producing skin equivalents that contain follicles, we suggest that the failure of cultured dermal papilla cells to induce follicle formation in wounds illustrates the complex role the follicle dermis may play in skin. We believe that it demonstrates a genuine dichotomy of activity for follicle cells within skin.     

Cosmetics in blacks

Blacks comprise a phenotypically heterogeneous group with respect to skin and hair. They are uniquely multihued with at least 35 different possible shades of pigmentation, and there is considerable variability in hair texture. This accounts for many of the unique skin and hair cosmetic requirements and customs in the black race. These grooming practices may present perplexing problems for the dermatologist when viewed in the context of resultant skin disease; therefore, an awareness and understanding of skin and hair products used by blacks, grooming techniques, and their consequences are essential for clinicians caring for black patients.