A systematic review of the literature on the treatment of pityriasis rubra pilaris type 1 with TNF-antagonists.

BACKGROUND: Adult pityriasis rubra pilaris (PRP) type 1 is a rare chronic papulosquamous disorder with clinical and histological parallels with psoriasis. Treatment is challenging and recent case reports suggest a potential role for tumour necrosis factor (TNF) antagonists. OBJECTIVES: Our objective was to systematically review the literature for evidence of efficacy of TNF antagonists in the treatment of adult PRP. METHODS: We performed a systematic search of the Cochrane library, EMBASE, Pubmed and MEDLINE databases. We defined diagnosis of PRP, classified clinical response and whether this was clearly attributed to TNF-antagonists. We also reviewed disease, treatment duration and follow up. RESULTS: Sixteen articles were selected for detailed review. From these, 12 articles (13 cases) met our predefined criteria and were included in the systematic review. The authors identified two more cases from their personal archive. A total of 15 evaluable cases were included for analysis. Twelve showed complete response (CR) (80%) to TNF-antagonists with a mean time to maximal response of 5 months. In 10 of the CR cases (83%) this was clearly attributable to TNF antagonist therapy. CONCLUSION: These data indicate that TNF-antagonists may be of value in treating adult type 1 PRP refractory to other systemic agents but selective reporting bias, together with the lack of standard diagnostic criteria and established spontaneous resolution in PRP, prevent any firm recommendations on their place in management.

Erythema gyratum repens associated with pityriasis rubra pilaris.

Erythema gyratum repens (EGR) is a rare cutaneous eruption characterized by serpiginous morphology and a migrating scaly border. It is one of the most specific cutaneous paraneoplastic phenomena, and is associated with malignancy in most cases. We report a 46-year-old Afro-Caribbean man with the unequivocal clinical and histological features of pityriasis rubra pilaris (PRP). However, despite improvement on oral acitretin, the morphology of the eruption evolved into the striking serpiginous rash of EGR. The histology findings, although nonspecific, were in keeping with the diagnosis of EGR. No evidence of malignancy was found. Only four cases of PRP evolving into EGR have been reported in the literature, and none was associated with malignancy. All previously reported cases of EGR have been described in white patients, making our case the first reported exception, to our knowledge. The possible role of retinoids in altering the rash of PRP to that of EGR is discussed.

Pityriasis rubra pilaris type 1 spontaneously resolving after 20 years.

Pityriasis rubra pilaris (PRP) is an uncommon, idiopathic, papulosquamous eruption. We report a longitudinal study of a patient with PRP type 1 who was treated with retinoid therapy for 9 years and whose symptoms resolved spontaneously after 20 years. There are no data in the literature on the disease course of PRP type 1 persisting beyond the usual 3 years. This case highlights both the extreme chronicity of PRP and the possibility of remission after many years of active disease.

An unusual patient with Rothmund-Thomson syndrome, porokeratosis and bilateral iris dysgenesis.

Rothmund-Thomson syndrome (RTS) is a rare autosomal recessive genodermatosis characterized by poikiloderma and the variable presence of other features including skeletal and ocular abnormalities, ectodermal defects, and susceptibility to certain malignancies. We report a 40-year-old woman with known RTS who developed porokeratoses on her limbs in adulthood, an association that has not previously been reported. In addition, she had bilateral iris dysgenesis, which has only been described once before in RTS.

Multiple milia due to radiotherapy.

We report the appearance of multiple milia in a 61 year old woman appearing 7 years after irradiation for breast cancer. The lesions were confined to the irradiated field.

New mutations in keratin 1 that cause bullous congenital ichthyosiform erythroderma and keratin 2e that cause ichthyosis bullosa of Siemens.

The intermediate filaments of epithelial cells are formed by keratins, a family of structurally related proteins, which are expressed in pairs of acidic (type I) and basic (type II) polypeptides in a tissue- and differentiation-specific manner. Mutations in the genes encoding several keratins have been implicated in the pathogenesis of diseases of keratinization. We report molecular analysis of two patients with the rare autosomal dominant disorders bullous congenital ichthyosiform erythroderma (BCIE) and ichthyosis bullosa of Siemens (IBS). Previous studies have shown that these genodermatoses are due to mutations in the KRT1 and KRT2E genes, respectively. We report a new amino acid substitution mutation in codon 155 of KRT1 (valine to aspartic acid) in the conserved H1 domain of the protein in the patient with BCIE. We also report a novel amino acid substitution mutation in codon 192 of KRT2E (asparagine to lysine) in the conserved 1A helix initiation peptide of the protein in the patient with IBS. Our results demonstrate that these mutations are deleterious to keratin filament network stability and lead to specific clinical inherited disorders of keratinization.

Hay-Wells syndrome is caused by heterozygous missense mutations in the SAM domain of p63.

Hay-Wells syndrome, also known as ankyloblepharon-ectodermal dysplasia-clefting (AEC) syndrome (OMIM 106260), is a rare autosomal dominant disorder characterized by congenital ectodermal dysplasia, including alopecia, scalp infections, dystrophic nails, hypodontia, ankyloblepharon and cleft lip and/or cleft palate. This constellation of clinical signs is unique, but some overlap can be recognized with other ectodermal dysplasia syndromes, for example ectrodactyly--ectodermal dysplasia--cleft lip/palate (EEC; OMIM 604292), limb--mammary syndrome (LMS; OMIM 603543), acro-dermato-ungual-lacrimal-tooth syndrome (ADULT; OMIM 103285) and recessive cleft lip/palate--ectodermal dysplasia (CLPED1; OMIM 225060). We have recently demonstrated that heterozygous mutations in the p63 gene are the major cause of EEC syndrome. Linkage studies suggest that the related LMS and ADULT syndromes are also caused by mutations in the p63 gene. Thus, it appears that p63 gene mutations have highly pleiotropic effects. We have analysed p63 in AEC syndrome patients and identified missense mutations in eight families. All mutations give rise to amino acid substitutions in the sterile alpha motif (SAM) domain, and are predicted to affect protein--protein interactions. In contrast, the vast majority of the mutations found in EEC syndrome are amino acid substitutions in the DNA-binding domain. Thus, a clear genotype--phenotype correlation can be recognized for EEC and AEC syndromes.

Netherton's syndrome: increased likelihood of diagnosis by examining eyebrow hairs.

Netherton's syndrome is a rare autosomal recessive condition with variable expression. It comprises an ichthyosiform dermatitis and erythroderma of variable intensity and manifestations, associated with hair abnormalities. The pathognomonic finding (required for diagnosis) is that of trichorrhexis invaginata identified by light and scanning electron microscopic examination of hair shafts. This may be difficult to establish because the hair is sparse and not all hairs exhibit abnormalities. In one patient, cutaneous and hair problems had existed since infancy, and despite repeated examination of scalp hairs, the definitive diagnosis was made only by examining eyebrow hairs at the age of 30 years. We subsequently compared the number of diagnostic lesions found on scalp and eyebrow hairs from two other patients with previously diagnosed Netherton's syndrome. The density of lesions was greater in eyebrow than scalp hair, and furthermore, all eyebrow hairs had at least one lesion. It is proposed that microscopic examination, if possible, of both scalp and eyebrow hair from patients in whom Netherton's syndrome is suspected would increase the chance of a positive diagnosis.

Circumferential fingernail.

We describe a Brazilian girl with a congenital circumferential nail on her left ring finger associated with other bony and soft tissue abnormalities of the affected limb. The tubular nail plate resembling a punch biopsy has been described as a circumferential nail, an extremely rare congenital malformation that can be associated with other congenital anomalies. In our review of the literature, there have only been two previous reports of this unusual condition affecting the fingernails.

Allelic heterogeneity of dominant and recessive COL7A1 mutations underlying epidermolysis bullosa pruriginosa.

The inherited mechanobullous disease, dystrophic epidermolysis bullosa, is caused by type VII collagen gene (COL7A1) mutations. We studied six unrelated patients with a distinct clinical subtype of this disease, epidermolysis bullosa pruriginosa, characterized by pruritus, excoriated prurigo nodules, and skin fragility. Mutation analysis using polymerase chain reaction amplification of genomic DNA, heteroduplex analysis and direct nucleotide sequencing demonstrated pathogenetic COL7A1 mutations in each case. Four patients had a glycine substitution mutation on one COL7A1 allele (G1791E, G2242R, G2369S, and G2713R), a fifth was a compound heterozygote for a splice site mutation (5532 + 1G-to-A) and a single base pair deletion (7786delG), and a sixth patient was heterozygous for an out-of-frame deletion mutation (6863del16). This study shows that the molecular pathology in patients with the distinctive clinical features of epidermolysis bullosa pruriginosa is heterogeneous and suggests that other factors, in addition to the inherent COL7A1 mutation(s), may be responsible for an epidermolysis bullosa pruriginosa phenotype.

The red face-an overview and delineation of the MARSH syndrome.

The problem of the red face in females is reviewed. After excluding common causes such as contact dermatitis, seborrhoeic eczema and photodermatitis the diseases affecting the remaining patients fall into three groups: marked erythema with no feeling of heat or sensitivity, usually erythromelanosis faciei; marked flushing and burning with intense sensitivity for which the term facial erythrodysaesthesia is proposed; the so-called MARSH syndrome in which an overlap of androgen-dominant symptoms occurs - melasma, acne, rosacea, seborrhoeic eczema, and hirsutism. The latter group may respond best to low dose oral isotretinoin.

The inherited palmoplantar keratodermas.

The inherited palmoplantar keratodermas (PPK) constitute a complex heterogeneous group of genodermatoses, which are difficult to classify clinically. The application of modern molecular biology techniques are leading to an increased understanding of the genetic bases of these disorders and are paving the way towards a classification based upon molecular pathology. We review the recent research advances in this field and the implications for development of novel approaches to disease management.

Multiple endocrine neoplasia type 1 presenting as rosacea.

We present a case of malignant carcinoid initially diagnosed as rosacea. This patient was later found to have an additional functioning parathyroid tumour. Although a pituitary tumour was not identified, the association represents a probable case of multiple endocrine neoplasia type 1 (MEN 1). This autosomal dominant syndrome is characterized by tumours of the pancreas, parathyroid and pituitary. Inoperable carcinoid tumour is best treated with a long-acting somatostatin analogue, octreotide. A diagnosis of MEN 1 has important connotations for the proband's first-degree relatives, who should be entered into an appropriate screening programme.

Reticulate acropigmentation of Dohi.

Two cases of reticulate acropigmentation of Dohi are reported, both patients demonstrating the typical features of this disorder. Reticulate acropigmentation of Dohi (dyschromatosis symmetrica hereditaria or symmetrical dyschromatosis of the extremities) is characterized by pigmented and depigmented macules mixed in a reticulate pattern on the extremities. It was first described in 12 patients from Japan, where it appears to be a well-established condition. Patients have been reported from Europe and a family from India has recently been described. We report two cases of reticulate acropigmentation of Dohi occurring in an Afro-Caribbean and an Indian patient, in order to alert clinicians to the possibility that this disorder may present in the UK.