Confluent and reticulated papillomatosis without papillomatosis

Confluent and reticulated papillomatosis is a papulosquamous disorder that affects young individuals. There are several hypotheses regarding the cause, including genetic keratinization disorder, reaction to pityrosporum, and reaction to UV light. Multiple therapeutic agents have been used with variable success. The histologic findings include papillomatosis, hyperkeratosis, and minimal or no acanthosis. We present a patient with the clinical findings of confluent and reticulated papillomatosis who responded dramatically to minocycline, and in whom histologic examination did not reveal papillomatosis.     

Linear porokeratosis: a case report and review of the literature

Linear porokeratosis refers to 1 of 5 variants of porokeratosis. Porokeratosis is a keratinization disorder of multiple etiologies including genetic aberrancy, trauma, and infection. We review a case of a 35-year-old man with a chronic history of linear porokeratosis and conduct a review of porokeratosis subtypes, etiology, histology, pathology, differential diagnosis, and treatment.     

Acantholytic dyskeratotic naevi following Blaschko''s lines: a mosaic form of Darier''s disease

Darier's disease (DD) is an autosomal-dominant skin disorder characterized by loss of adhesion between epidermal cells and abnormal keratinization. Several patients with unilateral, linear, 'zosteriform' or localized lesions have been reported. We report three cases of DD in a localized pattern corresponding to mosaicism type 1 according to Happle's classification and review the literature about the genetic cause of DD and DD in a 'zosteriform' pattern.     

Dermatologic, periodontal, and skeletal manifestations of Haim-Munk syndrome in two siblings

Haim-Munk syndrome is an extremely rare autosomal recessive disorder of keratinization characterized clinically by palmoplantar hyperkeratosis, severe early onset periodontitis, onychogryphosis, pes planus, arachnodactyly, and acro-osteolysis. Recently, germline mutations in the lysosomal protease cathepsin C gene have been identified as the underlying genetic defect in Haim-Munk syndrome and in the clinically related disorders, Papillon-Lefèvre syndrome and prepubertal periodontitis.     

Biomolecular advances in hereditary epidermal disorders

In recent years, the genes responsible for many hereditary skin diseases have been discovered. These genes encode different proteins that participate in the terminal differentiation of the epidermis, so their alteration or absence causes a keratinization disorder and/or an increase in skin fragility. Thanks to genetic analyses, we have been able to understand the physiopathology of numerous genodermatoses and we have become closer to diagnosing many others. In the not-too-distant future, biomolecular techniques may foreseeably help us prevent and treat these processes, which include skin diseases as serious as epidermolysis bullosa or epidermolytic hyperkeratosis. In this article, we will study the most recent biomolecular findings referring to keratinization and epidermal disorders, mentioning the altered genes and/ or the defective proteins that cause them.     

Two cases of KRT1 mutation-associated epidermolytic ichthyosis without typical epidermolytic hyperkeratosis in the neonatal skin lesions

Epidermolytic ichthyosis (EI) is a rare genetic disorder of keratinization caused by mutations in either KRT1 or KRT10. Histopathologically, epidermolytic hyperkeratosis (EHK) is a hallmark of EI. Here, we report two EI cases in which KRT1 mutation was confirmed by molecular study, but without typical EHK present on skin biopsies performed within 1 week of age. Our cases demonstrate that EHK may not be evident in EI if skin biopsy is performed during the neonatal period.     

Minute aggregate keratoses—a report of three cases

A new, possibly genetic disorder of keratinization is described. The condition is characterized by the truncal distribution of multiple minute keratotic papules. Morphologically these may be spicular or dome-shaped and aggregation of some of the latter creates the impression of annular and crateritbrm lesions. Histologically there are focat areas of hyperkeratosis and orthokeratosis with no dermal infiltrate. Odland bodies arc present on electron microscopy of lesional skin. The differential diagnosis of this condition is discussed.     

Trastornos autoinflamatorios de la queratinización

Autoinflammatory keratinization disease (AiKD) is a novel clinical concept encompassing diseases with a genetic background and mixed pathogenic mechanisms of autoinflammation and autoimmunity, leading to an aberrant keratinization of the skin. Recent advances in medical genetics have revealed genetic causes and/or predisposing factors for a number of AiKD's, such as mutations in IL36RN related with pustular psoriasis, acrodermatitis continua and hidradenitis suppurativa, in CARD14 in pityriasis rubra pilaris type V and some forms of pustular psoriasis, and in NLRP1 related with familial keratosis lichenoides chronica (KLC). It is suspected that AiKD pathophysiology would also be involved in non-monogenic disorders. The bidirectional relationship between inflammation and keratinization should be understood in order to outline optimal management, and new drug development should take both targets into account. We assume that new inflammatory keratinization diseases may be recognized as AiKDs in the coming years.     

X-linked ichthyosis: an update

X-linked ichthyosis is a genetic disorder of keratinization characterized by a generalized desquamation of large, adherent, dark brown scales. Extracutaneous manifestations include corneal opacity and cryptorchidism. Since 1978 it has been known that a deficit in steroid sulphatase enzyme (STS) is responsible for the abnormal cutaneous scaling, although the exact physiological mechanism remains uncertain. The STS gene has been mapped to the distal part of the short arm of the X chromosome. Interestingly, this region escapes X chromosome inactivation and has the highest ratio of chromosomal deletions among all genetic disorders, complete deletions having been found in up to 90% of patients. Diagnosis of patients with X-linked ichthyosis and female carriers is based on biochemical and genetic analysis. The latter currently seems to be the most accurate method in the majority of cases.     

Olmsted syndrome: report of two new cases and literature review

Olmsted syndrome is a rare keratinization disorder; 18 cases have been published so far. It associates a mutilating cogenital palmoplantar keratoderma with periorificial erythematokeratotic lesions. We report herein two new unrelated male children with Olmsted syndrome (OS), one of whom was studied by light and electron microscopy. Our histological, immunohistochemical, and ultrastructural findings suggest that this disease is related to epidermal hyperproliferation. We present herein a review of the twenty cases published so far and discuss the major clinicopathological and genetic features of this disease.     

Abnormal fibrous protein isolated from the stratum corneum of a patient with bullous congenital ichthyosiform erythroderma (BCIE)

Summary The fibrous protein of stratum corneum was isolated from a patient with bullous congenital ichthyosiform erythroderma (BCIE), and its properties characterized using electron microscopy, amino acid analysis and SDS gel electophoresis. Results were compared with the characteristics of the fibrous protein isolated from stratum corneum of normal controls.From 900 mg (dry weight) of stratum corneum, 68 mg of fibrous protein was obtained from the patient, while 178 mg was obtained from the normal control. Structural differences were observed with electron microscopy and chemical differences were shown in the ratio of several amino acids. On SDS electrophoresis, the 55,000 dalton constituent of normal fibrous protein could not be identified in the fibrous protein from this patient. These results suggest that an alteration of the polypeptide composition of fibrous protein from this patient with BCIE occurred, and this alteration induced the morphological and clinical features of this dominant genetic keratinization disorder.This study was supported by a research grant for genetic keratinization disorders (H.O.) from the Ministry of Health and Welfare of Japan and by a research grant for biochemical mechanisms of keratinization (H.O.) from Japan Lydia O'Leary Memorial Foundation in 1978     

Multiple minute digitate hyperkeratoses report of two cases with an updated review and proposal for a new classification.

Multiple minute digitate hyperkeratoses (MMDH) is a relatively rarely described disorder of keratinization of unknown origin. We noticed that MMDH has been reported in the literature under a variety of synonyms. We observed two patients with MMDH and reviewed the literature. We concluded that MMDH is a skin disorder which can be properly separated from other disorders of keratinization and classified as a distinct entity. Two forms of MMDH exist: MMDH of early onset and MMDH of late onset. Both forms are described occurring in a widespread and in a localized pattern. The early onset form may be hereditary, the late onset form may present as part of a paraneoplastic syndrome.     

Cytokeratin and filaggrin expression in nevus comedonicus

To elucidate the pathogenesis of abnormal keratinization in nevus comedonicus, we performed an immunohistochemical study using antikeratin and antifilaggrin (filament-aggregating protein) antibodies. There were no significant differences between nevus comedonicus and normal skin in cytokeratin expression. Although filaggrin was only detected in the granular layer in open comedones, filaggrin was detected in both superficial cells and also intermediate cells in closed comedones, suggesting that filaggrin is involved in the formation of closed comedones. The disorder of terminal differentiation related to filaggrin may play a role in the pathogenesis of abnormal keratinization in nevus comedonicus.     

In vivo abnormal keratinazation in Darier-White's disease as viewed by real-time confocal imaging

Darier-White's disease is a rare autosomal-dominant disorder of keratinization. The underlying pathology for the clinical presentation is acantholysis, and various types of dyskeratosis and acanthosis. In this study, we utilized a non-invasive optical imaging modality, confocal reflectance microscopy, to identify specific histologic features of Darier-White's disease in vivo. Micrographic findings in the confocal images were corps ronds, suprabasal clefts, acantholytic suprabasal keratinocytes, and villi. Real-time confocal images are illustrative and can be well correlated with known light microscopic phenomena, particularly in the case of keratinization abnormalities in Darier-White's disease.     

Punctate Porokeratosis Palmaris et Plantaris

Porokeratosis, a keratinization disorder, is probably a group of unrelated conditions with same distinctive histological appearance, featuring cornoid lamellae. A case of punctate porkeratosis in a 24 year old male patient is reported for its rarity.     

Epidermolytic palmoplantar keratoderma in a Hispanic kindred resulting from a mutation in the keratin 9 gene

Epidermolytic palmoplantar keratoderma (EPPK) is a localized keratinization disorder caused by mutations in the highly conserved coil 1A domain of the keratin 9 gene, KRT9. We present a Hispanic pedigree spanning three generations, with affected individuals in all generations. Using polymerase chain reaction amplification and direct sequencing we demonstrated a previously reported missense mutation in KRT9, which is expressed almost exclusively in the skin of palms and soles. The C-->T missense mutation R162W changes a basic amino acid (arginine) to a neutral amino acid (tryptophan). We describe this mutation in a Hispanic pedigree with EPPK for the first time, extending the finding of this mutation in other genetic backgrounds, and demonstrating the prevalence of this mutation in diverse populations.     

Male-pattern baldness is common in men with X-linked recessive ichthyosis

BACKGROUND: X-linked recessive ichthyosis (XRI) is a relatively common genetic disorder of keratinization caused by deficiency in steroid sulfatase (STS) activity. STS appears to play an important role in testosterone metabolism. Therefore it has been discussed that the presence of normally functioning STS may be a presupposition for the development of androgenetic alopecia (AGA). METHODS: Patients with the diagnosis of XRI were sent questionnaires. RESULTS AND CONCLUSIONS: We reviewed 26 cases with XRI and noticed 11 patients with AGA in an advanced stage. The existence of two pathways for the steroid biosynthesis may be the explanation for a compensatory mechanism in XRI males. The Delta5 pathway depends on steroid sulfate activity, whereas the working Delta4 pathway produces AGA in XRI males.     

Penile terra firma-forme dermatosis in children

Terra firma-forme dermatosis (TFFD) is a rare, acquired keratinization disorder that predominantly affects children and young adults. Herein, we report three unusual cases of penile TFFD in children and the histopathologic and ultrastructural observations.     

Hyperkeratosis lenticularis perstans (Flegel's disease)

A 62-year-old female with a 20-year history of small horny papules on the skin of the legs is described. Light microscopy revealed a hyperkeratotic papule with atrophic epidermis and a dense dermal inflammatory cell infiltrate with many cerebriform lymphocytes not earlier described in connection with hyperkeratosis lenticularis perstans (HLP). The electron-microscopic picture showed membrane-coating granules (MCG) and keratohyalin located in different cells, indicating that the disorder of keratinization in HLP is possibly caused by reduced co-operation between these cells and that the keratinization process occurs in the absence of MCG. Perpetual treatment with oral retinoid was successful.     

Nonmutilating palmoplantar and periorificial kertoderma: a variant of Olmsted syndrome or a distinct entity?

Background Olmsted syndrome is a rare keratinization disorder characterized by mutilating palmoplantar and periorificial keratoderma as the two major diagnostic features. Some authors believe that atypical cases without this standard combination may not really belong to Olmsted syndrome. Herein, we describe two familial cases with congenital nonmutilating palmoplantar and periorificial keratoderma, and discuss their similarities and differences with Olmsted syndrome. Patients The study included two sisters who presented with focal and punctate nonmutilating palmoplantar keratoderma (PPK), periorificial hyperkeratotic plaques, and widely distributed keratotic lesions. Fragile denuded areas of the skin were found in sites exposed to trauma. Fingernails showed a characteristic form of leukonychia. Results Histopathology of plantar keratoderma showed psoriasiform hyperplasia with marked compact hyperkeratosis, while vicinity of denuded skin revealed thin parakeratotic zone and dissolution of the granular cell layer. Immunohistochemistry demonstrated suprabasal staining pattern for acidic keratin (AE1) and uniform positivity, starting four to six layers above the basal layer, for cytokeratin 10. Electron microscopy showed defective keratinization. Cytogenetic studies revealed normal karyotype and no chromosomal breakage. Conclusion Our cases share Olmsted syndrome in the early onset, and the presence of symmetrical PPK, periorificial keratoderma and keratotic lesions. However, the striking nonmutilating nature of PPK and the presence of unique features in our patients suggest a newly described keratinization disorder.