Alopecia areata incognita in Cronkhite-Canada syndrome.

Cronkhite-Canada syndrome is an acquired inflammatory polyposis syndrome in which alopecia, onychomadesis and hyperpigmentation occur concurrently with gastrointestinal symptoms. The pathophysiology of alopecia in Cronkhite-Canada syndrome has not been definitively elucidated. We present evidence for alopecia areata incognita as a possible mechanism of hair loss.

Propranolol in the treatment of infantile haemangiomas: lessons from the European Propranolol In the Treatment of Complicated Haemangiomas (PITCH) Taskforce survey.

BACKGROUND: Oral propranolol is widely prescribed as first-line treatment for infantile haemangiomas (IHs). Anecdotally, prescribing practice differs widely between centres. OBJECTIVES: The Propranolol In the Treatment of Complicated Haemangiomas (PITCH) Taskforce was founded to establish patterns of use of propranolol in IHs. METHODS: Participating centres entered data on all of their patients who had completed treatment with oral propranolol for IHs, using an online data capture tool. RESULTS: The study cohort comprised 1097 children from 39 centres in eight European countries. 76·1% were female and 92·8% had a focal IH, with the remainder showing a segmental, multifocal or indeterminate pattern. The main indications for treatment were periocular location (29·3%), risk of cosmetic disfigurement (21·1%) and ulceration and bleeding (20·6%). In total 69·2% of patients were titrated up to a maintenance regimen, which consisted of 2 mg kg(-1) per day (85·8%) in the majority of cases. 91·4% of patients had an excellent or good response to treatment. Rebound growth occurred in 14·1% upon stopping, of whom 53·9% were restarted and treatment response was recaptured in 91·6% of cases. While there was no significant difference in the treatment response, comparing a daily maintenance dose of < 2 mg kg(-1) vs. 2 mg kg(-1) vs. > 2 mg kg(-1) , the risk of adverse events was significantly higher: odds ratio (OR) 1 vs. adjusted OR 0·70, 95% confidence interval (CI) 0·33-1·50, P = 0·36 vs. OR 2·38, 95% CI 1·04-5·46, P = 0·04, Ptrend < 0·001. CONCLUSIONS: The PITCH survey summarizes the use of oral propranolol across 39 European centres, in a variety of IH phases, and could be used to inform treatment guidelines and the design of an interventional study.

Genetic modeling of abnormal photosensitivity in families with polymorphic light eruption and actinic prurigo.

Actinic prurigo and polymorphic light eruption are two of the so-called idiopathic photodermatoses, resulting from abnormal cutaneous responses to ultraviolet radiation (photosensitivity). Whereas they are clinically distinct in most cases, there are sufficient similarities between them to suggest they may be related conditions. To take this further, we examined the prevalence of polymorphic light eruption in families ascertained through actinic prurigo probands, as evidence of a shared pathogenesis. We then determined the heritability of photosensitivity in 420 individuals from families ascertained through polymorphic light eruption and actinic prurigo probands using segregation analysis. Across 58 pedigrees the prevalence of photosensitivity in first-degree relatives was 20.9% compared with a population prevalence of 13.6%, giving a relative risk of 1.5 (confidence interval 1.15-2.0) and providing evidence of clustering within families. The prevalence of photosensitivity (predominantly polymorphic light eruption) in relatives of actinic prurigo probands was 23.7%, with a relative risk of 1.74 (confidence interval 1.24-2.36). Modeling for polymorphic light eruption across all pedigrees revealed a strong genetic component with polymorphic light eruption showing a dominant mixed mode of inheritance. The model parameters estimate that 72% of the U.K. population carry a low penetrance polymorphic light eruption susceptibility allele, but that among this highly prevalent genotype only 24% of susceptible females and 13% of susceptible males will have polymorphic light eruption. Expression of polymorphic light eruption in genetically susceptible individuals (intergenotype variance) is determined in large part by a polygenic component, with an important additional environmental component. In summary, this study provides clear evidence that polymorphic light eruption is an inherited condition. It also suggests that polymorphic light eruption and actinic prurigo share a common genetic background, supporting the view that actinic prurigo may represent a human leukocyte antigen-restricted subset of polymorphic light eruption.

What is actinic prurigo in Britain?

Actinic prurigo (AP) belongs to the group of idiopathic photodermatoses sharing a predilection for occurring more commonly in females, and there is much controversy as to whether it is only a more severe form of polymorphous light eruption (PMLE) or whether it is a distinct entity in its own right. The condition is characterised by intensely itchy papules, plaques and nodules, along with excoriations and scars usually starting before puberty, and predominantly involves the sun-exposed areas although it may also affect covered sites. Seasonal exacerbations at the beginning of spring with improvement in the fall are typical, although the lesions frequently do not clear completely in the winter. The disorder may run a chronic course and persist into adulthood, but often spontaneous resolution occurs in late adolescence. Diagnosis is predominantly based on the clinical features, cutaneous irradiation tests and histology often being normal or non-specific. HLA typing has also been performed in both PMLE and AP patients, showing a strong association between HLA-DR4, in particular with the DRB1*0407 subtype, and AP; no HLA association has been found in PMLE. This HLA association is likely to be of pathogenic significance and strongly suggests a critical role for MHC-restricted antigen presentation in the development of photosensitivity AP.

Late onset variegate porphyria.

Variegate porphyria (VP) first presenting in old age is uncommon and should raise the possibility of an underlying precipitating cause. This case report documents VP in an elderly woman with a liver tumour.

Rosai-Dorfman disease complicated by autoimmune haemolytic anaemia: case report and review of a multisystem disease with cutaneous infiltrates.

We report a patient with sinus histiocytosis with massive lymphadenopathy (Rosai-Dorfman disease) who presented with widespread nodal and extranodal involvement affecting the skin, orbits and nasal sinuses, complicated by the development of autoimmune haemolytic anaemia. The aetiology and pathogenesis of this multisystem disorder are unknown but are thought to represent a reactive histiocytic process to an infective agent rather than a neoplastic or other primary condition. Prognosis is generally good but clinical or laboratory evidence of immune dysfunction tends to predict a poorer outcome. We describe the clinical course of the patient and review the literature on this disease.

Actinic prurigo and polymorphic light eruption: common pathogenesis and the importance of HLA-DR4/DRB1*0407.

Actinic prurigo (AP) and polymorphic light eruption (PLE) both belong to the group of idiopathic photodermatoses, but it remains controversial whether AP is a distinct photodermatosis or a variant of PLE. The aim of this study, by collecting data from 119 patients with features of these disorders, was to establish whether specific criteria could be used to distinguish AP from PLE prospectively. We found that presence of the eruption on both exposed and covered sites, its occurrence in winter, persistence of lesions beyond 4 weeks, mucosal and conjunctival involvement, excoriation and scarring of the skin were important features of AP which were not typical of PLE. On this basis, confident clinical diagnoses could be reached in 103 of 119 patients (87%), 57 with AP and 46 with PLE, supported by phototesting and negative lupus serology. HLA typing subsequently confirmed the strong association (90%) between AP and the DR4 allele, in particular with the rare subtype DRB1*0407 which was present in 60% of these patients. No HLA association was found in PLE. In the 16 remaining cases, however, clinical overlap meant that no definite diagnosis could be made; these patients were notionally described as having persistent PLE (PPLE). Demographic and HLA data in this group suggested that PPLE was perhaps most appropriately grouped with PLE. In addition to those patients who were difficult to classify, 35% of our typical AP patients also described clinical progression from PLE to AP, AP to PLE or coexistence of both AP and PLE. In conclusion, our study suggests that while AP and PLE are clinically distinct conditions in most cases, they may perhaps share a common pathophysiological basis. The AP phenotype may be determined by HLA and perhaps other factors in patients otherwise predisposed to PLE.

The perils and pitfalls of penile injections.

We describe a 45-year-old man who presented with an indurated penile nodule following self-injection of acyclovir tablets which he had dissolved in hydrogen peroxide solution. This is a hazardous procedure which may be complicated by permanent deformity and functional disability due to the irritant nature of the tablets' constituents and their propensity to cause foreign body reactions in the skin.

Tumour necrosis factor alpha promoter polymorphism at position -308 is not associated with actinic prurigo.

Actinic prurigo (AP) has been found to be strongly associated with HLA DR4 and in particular with the DR4 subtype DRB1*0407. However, AP may occur in the absence of HLA-DR4. Furthermore, it has been shown that HLA-DR4 and DRB1*0407, even in association with polymorphic light eruption (PLE), are insufficient for the expression of the AP phenotype. It seems likely, therefore, that other genes in the HLA DR or adjacent regions may contribute to AP susceptibility. One possible predisposing factor in AP may be tumour necrosis factor (TNF)alpha as suggested by the good response of AP to the TNFalpha inhibitor thalidomide, and by the involvement of this cytokine in many immune responses. The aim of this study was to explore the relationship between AP and TNFalpha by examining the frequency of TNF2 in patients with AP, PLE and in normal controls. TNF1 and TNF2 are biallelic polymorphisms at position -308 of the TNFalpha gene promoter and are known to affect transcription of TNFalpha. TNF2 is the rarer of the two alleles and is associated with high functional levels of TNFalpha. This study confirms the positive linkage disequilibrium that has been described between HLA DR3 and TNF2, but fails to show an association between TNF2 and AP.

A candidate gene analysis of three related photosensitivity disorders: cutaneous lupus erythematosus, polymorphic light eruption and actinic prurigo.

BACKGROUND: Polymorphic light eruption (PLE) is a common inherited photosensitivity disorder, which may predispose to several related but distinct conditions, including subacute cutaneous lupus erythematosus (SCLE), discoid lupus erythematosus (DLE) and actinic prurigo (AP). OBJECTIVES: To examine specific candidate genes for shared susceptibility alleles between these related phenotypes. METHODS: Eighty-five caucasian patients with annular SCLE or DLE were recruited, in addition to 102 first-degree relatives. The prevalence of PLE in both the patient and relative groups was determined by detailed interview and clinical examination. Eighty-five patients with pure PLE and 59 patients with AP were also recruited. Candidate genes were analysed by typing of single nucleotide polymorphisms of IL10 (-1082 G/A and -819 C/T), FCGR2A (131 R/H), SELE (128 S/R), ICAM1 (241 G/R and 469 E/K), IL1A (+ 4845 G/T), IL1B (-511 C/T and + 3954 C/T), IL1RN (+ 2018 T/C) and TNF (-308 G/A) using polymerase chain reaction (PCR) with sequence-specific primers and 5'-nuclease PCR. RESULTS: A significant association was found between SCLE and the rare TNF -308 A allele when compared with patients with DLE (P = 0.043), PLE (P = 0.001), AP (P < 0.001) and healthy controls (P < 0.001). However, there was strong linkage disequilibrium between TNF -308 A and the HLA A*01, B*08, DRB1*0301 haplotype. A negative association was also found between SCLE and the IL1B + 3954 T allele (P = 0.039), but the significance was lost on correction for multiple testing. CONCLUSIONS: We have demonstrated the association of SCLE with the rare TNF -308 A allele, which may be pathogenic or, alternatively, a marker allele for the extended HLA A*01, B*08, DRB1*0301 haplotype that is associated with a number of autoimmune conditions. Although many of the other loci that we chose failed to demonstrate an association, a candidate gene approach remains the most logical one, and the most likely to yield positive results in the future.