掌跖棘状角皮症——一见难忘

本文介绍了1例83岁的男性患者,掌跖角化性丘疹病史5年,症状为在手掌出现长度为1～2mm,直径为0．5～1．5mm不等的角化性丘疹,脚掌相同皮损较少,未接受治疗,无家族病史。患者既往患有肺石棉沉着病（职业病）、2型糖尿病、高血压、高胆固醇血症、阵发性房颤、进行性慢性肾功能衰竭。自2004年以来,患者一直在皮肤科治疗复发性非黑色素瘤皮肤癌症。     

Aquagenic (pseudo) keratoderma (aquagenic palmoplantar keratoderma,aquagenic wrinkling of palms)

Aquagenic palmoplantar keratoderma (APK) is an uncommon hereditary or sporadic condition that is characterized by edematous flat-topped papules appearing on palmar skin with wrinkling after brief water exposure. APK has been associated with cystic fibrosis (CF), presenting with the same mutations found in CF (usually ΔF508 of the CFTR gene), either homozygous or heterozygous. APK may be idiopathic or drug-induced. The diagnosis is easily made if one is aware of this entity. Topical aluminum hydroxide and botulinum toxin injections are the most commonly used treatments. The sporadic form may have a shorter course compared with the hereditary one, resolving spontaneously after a few years. The condition should no longer be considered a true keratoderma but rather a pseudo keratoderma, and in spite of the many different names found in the literature, the term “aquagenic (pseudo) keratoderma” seems to be the most appropriate one.     

Epidermolysis bullosa simplex with keratoderma of the palms and soles

A family is described who had epidermolysis bullosa (EB) simplex (Koebner) associated with keratoderma of the palms and soles. This association has been infrequently reported in the literature. The keratoderma appears to have a protective effect as these patients developed few palmar and plantar blisters in the area of the keratoderma. EB simplex (Koebner) with keratoderma appears to be a distinct syndrome, but the simultaneous occurrence of two dominantly inherited traits cannot be excluded.     

Spiny keratoderma of the palms: a case study

Spiny keratoderma of the palms is an infrequent entity of unknown etiology. Most of the cases described are acquired, but there are also family cases. This dermatosis is characterized by the appearance of hyperkeratotic, generally asymptomatic, projections on the palms and/or soles, measuring only a few millimeters. In the histological study, parakeratotic columns of cornoid lamellae were observed on an epidermis with a thin or absent granular layer. Its association with malignant tumor pathologies of different types has been described. We present a new case of this entity, which had the peculiarity of a relationship of the parakeratotic column with the acrosyringium in some histological sections, a finding typical of a porokeratotic eccrine ostial or dermal duct nevus.     

Spiky keratotic projections on the palms and fingers. Spiny keratoderma

Spiny keratoderma is an infrequent dermatosis consisting of multiple projections located on the palms and soles, with the distinct histopathology feature of a parakeratotic column above a hypogranular epidermis. This entity has been reported under several different names, such as punctate porokeratotic keratoderma, punctate keratoderma, palmar filiform hyperkeratosis, and spiny keratoderma of the palms and soles. Most of the cases described are acquired, although there are also familial cases. Since this disease has been under-diagnosed and under-reported, it is important for dermatologists to keep spiny keratoderma of the palms and soles in mind. We present a familial case of spiny keratoderma and review the literature.     

Spiny keratoderma of the palms and soles - report of two cases

We report two patients with spiny keratoderma of the palms and soles characterized by multiple tiny keratotic plugs on the palms and soles. This disease was reported to be possibly associated with internal malignancies. We found a tumor from the esophagus to cardia in one patient. Another had no tumor but the lesion occurred soon after a severe bronchial asthma attack. Causal relation between spiny keratoderma of the palms and soles and bronchial asthma is obscure. Since this disease has been under-diagnosed and under-reported, it is important for dermatologists to keep spiny keratoderma of the palms and soles in mind in daily clinical examinations.     

Acute or chronic topical retinoic acid treatment of human skin in vivo alters the expression of epidermal transglutaminase, loricrin, involucrin, filaggrin, and keratins 6 and 13 but not keratins 1, 10, and 14.

Histologic and immunocytochemical analyses were performed on cutaneous biopsies from 10 patients treated with retinoic acid under occlusion for 4 d compared to biopsies from 19 patients treated nightly for 16 weeks. Acute application of RA caused epidermal thickening (9 of 10 samples), stratum granulosum thickening (7 of 10), parakeratosis (4 of 10), a marked increase in the number of cell layers expressing epidermal transglutaminase (7 of 10), and focal expression of two non-epidermal keratins, K6 (8 of 10) and K13 (2 of 10), changes also observed with chronic treatment. Involucrin, filaggrin, and loricrin were also altered in samples from both acute and chronic treatment. An increased number of cell layers expressed both involucrin and filaggrin from both the acute (7 of 10) and chronic (14 of 19) treatment groups. In the acute group, loricrin expression was significantly reduced or absent in some regions of the epidermis (5 of 10), whereas most chronic samples showed an increased number of cell layers expressing loricrin (12 of 19). The pattern of expression of three major epidermal differentiation products, keratins K1, K10, and K14, was not significantly altered in any of the acute or chronic samples, although there was a slight reduction in the detection of K10 in two of the acute samples. Thus, acute topical RA treatment under occlusion caused substantial changes in the epidermis, and reproduced most, but not all of the effects of chronic treatment.     

Expression of type I hair keratins in follicular tumours

BACKGROUND: Hair keratins are specifically expressed in hair and nails. We previously demonstrated the expression of hair keratin basic 1 mRNA in pilomatrixomas. We recently developed a method for immunohistochemical staining of the group of acidic keratins, which have not yet been investigated in human tumours. OBJECTIVES: To study the expression of eight members of the type I hair keratin subfamily in pilomatrixomas and other skin tumours of follicular origin. METHODS: We performed immunohistochemistry on paraffin sections of formalin-fixed pilomatrixomas (40), trichoepitheliomas (10), trichoblastomas (10), desmoplastic trichoepitheliomas (10) and basal cell carcinomas (10), using antibodies against type I hair keratins hHa1, hHa2, hHa3-II, hHa4, hHa5, hHa6, hHa7 and hHa8 as well as cytokeratin CK17. RESULTS: While CK17 was found in almost all tumours investigated, hair keratins were exclusively expressed in pilomatrixomas. Their expression was restricted to areas of transitional cells, located between outer basophilic matricial cells and an inner zone of eosinophilic shadow cells. The most frequently and most strongly expressed hair keratins were hHa1, hHa2, hHa5 and hHa8, whereas hHa4 and hHa6 were only weakly expressed. No positive staining was observed with anti-hHa3-II and anti-hHa7 antibodies. Hair keratin expression in intermediate maturation stage pilomatrixomas resembled that of normal hair follicles, with early matricial and cuticular keratins hHa5 and hHa2 being expressed in lower transitional cells, followed by expression of early cortex keratins hHa1 and hHa8 in intermediate transitional cells and the late cortex keratins hHa4 and hHa6 in upper transitional cells. The latter were, however, seen only in a few intermediate maturation stage pilomatrixomas and were generally absent in late-stage pilomatrixomas. CONCLUSIONS: These changes in hair keratin expression patterns indicate that the maturation of pilomatrixomas towards large areas of shadow cells is associated with a gradual loss of differentiation-specific hair keratins. The complex hair keratin expression in pilomatrixomas is a further argument in favour of a hair matrix origin of this tumour.     

Clinicopathological features and expression of four keratins (K10, K14, K17 and K19) in six cases of eruptive vellus hair cysts

Six cases of eruptive vellus hair cysts (EVHC) were evaluated for histopathology and the immunohistochemical profile of Ki‐67 and four keratins (K10, K14, K17 and K19). The pathological hallmark of EVHC was the existence of vellus hair shafts within the cystic cavity, but atypical pathological changes included two or three cysts and a foreign‐body granuloma in three cases. Our results demonstrate that atypical pathological changes are not uncommon in EVHC, and indicate that based on keratin expression, it is likely that EVHC is derived from the infrainfundibulum and sebaceous duct.     

发育不良痣皮损中P14ARF/P16β和gp100的表达

目的:探讨P14ARF/P16β和gp100等在发育不良痣(DN)皮损中的表达。方法:应用免疫组化方法,分别对9例DN、10例先天性色痣和10例普通获得性痣的石蜡组织标本,进行P14ARF/P16β和gp100等的检测。结果:在P14ARF/P16β标记中,DN与先天性色痣或普通获得性痣相比呈现低表达。在gp100标记中,DN与先天性色痣或普通获得性痣相比呈现高表达。结论:DN与先天性色痣或普通获得性痣相比,其P14ARF/P16β表达降低,可能与痣细胞不成熟相关,而DN中的gp100高表达,提示与痣细胞增生活跃相关。     

Exuberant clinical picture of Buschke-Fischer-Brauer palmoplantar keratoderma in bedridden patient

Buschke-Fisher-Brauer keratoderma is a rare hereditary autosomal dominant disease ofincomplete penetrance. Important differential diagnoses include other palmoplantarkeratinization disorders, acquired or hereditary, which is done based on thehistopathological findings. This diagnosis alerts especially about the possibility ofassociated neoplasms. Treatment involves topical keratolytic agents, usually withlittle efficacy, or with long-term systemic retinoids with follow-up of exuberantcollateral effects.     

Manifestation of diffuse yellowish keratoderma on the palms and soles in autosomal recessive congenital ichthyosis patients may be indicative of mutations in NIPAL4

Ichthyosis is a heterogeneous disorder characterized by abnormal skin scaling over the whole body. Autosomal recessive congenital ichthyosis (ARCI) comprises various forms, the most important of which are lamellar ichthyosis (LI) and congenital ichthyosiform erythroderma (CIE). Seven genes have been identified to be causative of ARCI, and these account for disease in 60-80% of the patients. There is notable phenotypic overlap between the major forms of ARCI, and a strong genotype-phenotype correlation has not been found. Here, we initially aimed to identify the causative gene in a large Iranian ARCI pedigree, and subsequently performed genetic analysis on four other affected pedigrees. A genotype-phenotype correlation was sought. Whole genome homozygosity mapping using high-density single nucleotide polymorphism chips was performed on the large pedigree. Linkage to chromosome 5 and a mutation in NIPAL4 causing p.G297R were identified. The same mutation was also identified in two of the remaining four Iranian pedigrees. Two of the NIPAL4 mutation bearing pedigrees were classified as CIE and one as LI. Notably, all NIPAL4 mutation-bearing patients manifested diffuse yellowish keratoderma on the palms and soles. We provide evidence suggesting presentation of this diffuse yellowish keratoderma may be indicative of mutations in NIPAL4, providing an easily assessable genotype-phenotype correlation.     

A spectrum of mutations in keratins K6a, K16 and K17 causing pachyonychia congenita

BACKGROUND: Pachyonychia congenita (PC) is a rare autosomal dominant keratin disorder, subdivided into two major variants, PC-1 and PC-2. Predominant characteristics include hypertrophic nail dystrophy, focal palmoplantar keratoderma and oral leukokeratosis. Multiple steatocystomas that develop during puberty are a useful feature distinguishing PC-2 from PC-1. At the molecular level it has been shown that mutations in keratin K6a or K16 cause PC-1 whereas those in K6b or K17 lead to PC-2. OBJECTIVE: To identify mutations in 22 families presenting with clinical symptoms of either PC-1/focal non-epidermolytic palmoplantar keratoderma (FNEPPK) or PC-2. METHODS: Mutation analysis was performed on genomic DNA from PC patients by direct sequencing. RESULTS: Here, we report four new missense and five known mutations in K6a; one new deletion and three previously identified missense mutations in K16; plus one known mutation in K17. CONCLUSION: With one exception, all these heterozygous mutations are within the highly conserved helix boundary motif regions at either end of the keratin rod domain. In one sporadic case, a unique mutation in K16 resulting in deletion of 24bp was found within the central rod domain, in a child with a phenotype predominantly consisting of focal plantar keratoderma. The identification of mutations in cases of PC is prerequisite for future development of gene-specific and/or mutation-specific therapies.