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Neutrophilic urticarial dermatosis (NUD), a particular clinical and histological entity, can provide a strong pointer to underlying systemic disease, most frequently rheumatological diseases. We report the first case of NUD in association with a post-streptococcal rheumatic disease, with symptoms including recurrent sore throat, raised antistreptolysin O titre, persistent transient urticaria, polyarthralgia, rheumatic mitral valve disease and Jaccoud arthropathy. Histologically, NUD is characterized by an intense superficial and deep neutrophilic interstitial and perivascular infiltrate, without significant oedema or blood vessel damage. These neutrophils may have a tendency to concentrate along the basement membrane and extend into the epidermis, hair follicles, sebaceous glands and sweat glands (a feature termed 'neutrophilic epitheliotropism'). Clinicians should remain cognizant of NUD, and in particular its frequent association with an underlying inflammatory disorder.

Background Xeroderma pigmentosum (XP) is a rare autosomal recessive disorder of DNA repair. It is divided into eight complementation groups: XP-A to XP-G (classical XP) and XP variant (XP-V). Severe and prolonged sunburn reactions on minimal sun exposure have been considered a cardinal feature of classical XP. However, it has recently become clear that not all patients have abnormal sunburn reactions. Objectives To examine sunburn reactions in a cohort of patients with XP and correlate this to the complementation group. Methods Sixty patients with XP attending the U.K. National XP Service from 2010 to 2012 were studied. Their history of burning after minimal sun exposure was assessed using a newly developed sunburn severity score. The age at which the first skin cancer was histologically diagnosed in each patient, and the presence of any neurological abnormality, was also recorded. Results Sunburn severity scores were abnormally high in patients with XP-A, XP-D, XP-F and XP-G compared with non-XP controls. There was no significant difference in sunburn score of patients with XP-C, XP-E and XP-V compared with controls (P > 0·05). Patients with XP-C, XP-E and XP-V were more likely to have skin cancer diagnosed at an earlier age than those with severe sunburn on minimal sun exposure. In addition, patients with XP with severe sunburn had an increased frequency of neurological abnormalities. Conclusions Not all patients with XP have a history of severe and prolonged sunburn on minimal sun exposure. The normal sunburn response of patients with XP-C, XP-E and XP-V may relate to the preservation of transcription-coupled DNA repair in these groups. Those with a history of severe sunburn on minimal sun exposure developed their first skin cancer at an older age compared with patients with XP-C, XP-E and XP-V, but they had an increased frequency of neurological abnormalities. Physicians need to be aware that about half of all patients with XP will present without a history of abnormal sunburn. What's already known about this topic? Xeroderma pigmentosum (XP) is a rare autosomal recessive disorder of DNA repair. It is characterized by pigmentary skin changes, significantly increased risk of skin cancer, and progressive neurological disease in about 25% of cases. It is subdivided into eight complementation groups: XP-A to XP-G (classical XP) and XP variant (XP-V). Severe and prolonged sunburn reactions on minimal sun exposure have previously been considered a cardinal feature of classical XP. Recent data from a cohort of patients with XP at the National Institutes of Health in the U.S.A. have shown that about a third of their patients with XP have never sunburned. What does this study add? Not all patients with classical XP have severe and prolonged sunburn reactions. There is a correlation between response to sun exposure and XP complementation group. Patients with XP-C, XP-E and XP-V have sunburn reactions normal for skin-type compared with unaffected controls. Physicians need to be aware that about half of all patients with XP will present without a history of abnormal sunburn. This has important diagnostic and prognostic implications. See also the Commentary by Kraemer et al

Xeroderma pigmentosum (XP) is a rare DNA repair disorder characterized by increased susceptibility to UV radiation (UVR)-induced skin pigmentation, skin cancers, ocular surface disease, and, in some patients, sunburn and neurological degeneration. Genetically, it is assigned to eight complementation groups (XP-A to -G and variant). For the last 5 y, the UK national multidisciplinary XP service has provided follow-up for 89 XP patients, representing most of the XP patients in the United Kingdom. Causative mutations, DNA repair levels, and more than 60 clinical variables relating to dermatology, ophthalmology, and neurology have been measured, using scoring systems to categorize disease severity. This deep phenotyping has revealed unanticipated heterogeneity of clinical features, between and within complementation groups. Skin cancer is most common in XP-C, XP-E, and XP-V patients, previously considered to be the milder groups based on cellular analyses. These patients have normal sunburn reactions and are therefore diagnosed later and are less likely to adhere to UVR protection. XP-C patients are specifically hypersensitive to ocular damage, and XP-F and XP-G patients appear to be much less susceptible to skin cancer than other XP groups. Within XP groups, different mutations confer susceptibility or resistance to neurological damage. Our findings on this large cohort of XP patients under long-term follow-up reveal that XP is more heterogeneous than has previously been appreciated. Our data now enable provision of personalized prognostic information and management advice for each XP patient, as well as providing new insights into the functions of the XP proteins.

Background Some patients with psoriasis may require hospital admission to stabilize their condition, although the role of inpatient management is changing given recent advances in therapeutic options, emphasis on community-based care for chronic conditions and limited healthcare resources. There is a need for evidence-based national standards for inpatient management of psoriasis taking account of factors that predict length of stay. Objectives To determine which factors predict length of stay for patients with psoriasis requiring inpatient hospital care with a view to setting evidence-based standards for inpatient psoriasis management. Methods A multicentre service review was conducted on all psoriasis admissions over a 9-month period in four dermatology centres in the U.K. We collected data on admission, at discharge and, where possible, at 3 months following discharge. Psoriasis severity was assessed using four validated scoring systems, including Psoriasis Area and Severity Index (PASI) and Dermatology Life Quality Index. We also recorded length of stay and treatment details. Results Length of stay varied widely between the four centres, but was similar in the two centres which received a high proportion of tertiary referrals for severe psoriasis (mean 19·7 days, range 1-78, analysis of variance P = 0·002). Disease severity, measured by PASI, on admission (mean 15·7, interquartile range 8·3-20·8) was significantly higher in the tertiary centres (P < 0·0001). However, there was no significant difference in PASI between centres on discharge. The admission PASI was significantly associated with length of stay (r = 0·2, P = 0·02). There was no significant correlation between other measures of disease severity and length of stay. Conclusions Disease severity on admission for patients with psoriasis is greater in tertiary referral centres for psoriasis and is directly associated with length of stay. Length of stay should be used in conjunction with clinical measures such as PASI improvement to set national standards for quality in secondary care.

Bessis et al1 describe what they believe to be a new syndrome, Bier's Anemic Spots associated with Cyanosis and Urticaria-Like Eruption. In doing so they have provided a nice description and beautiful pictures of orthostatic acrocyanosis (OA).2 They describe four cases, three of whom triggered the eruption after standing and one by mechanical pressure. There was a uniform background cyanosis in which pink macules were scattered. In the centre of some of these pink macules pinpoint to 1-2mm papules are seen. This article is protected by copyright. All rights reserved.

We report a case of dermatitis herpetiformis associated with bullous pemphigoid in which the clinical, histopathological and immunopathological findings were corroborated by direct immunoelectronmicroscopy performed on normal and peri-lesional skin biopsies. Western immunoblotting detected the 180 kDa BPAG2 consistent with bullous pemphigoid. HLA-typing confirmed the DR3 DQ2 haplotype associated with dermatitis herpetiformis.

We report two patients with renal failure who developed painful symmetrical ulceration over the proximal thighs and abdominal wall. Histological examination of the ulcerated areas revealed intravascular calcification. This phenomenon has been termed calciphylaxis and is a rare complication of renal failure. The pathogenesis is poorly understood. However, abnormalities of calcium/phosphate metabolism and of coagulation are important.

Cockayne syndrome (CS) is a genetic disorder characterized by developmental abnormalities and photodermatosis resulting from the lack of transcription-coupled nucleotide excision repair, which is responsible for the removal of photodamage from actively transcribed genes. To date, all identified causative mutations for CS have been in the two known CS-associated genes, ERCC8 (CSA) and ERCC6 (CSB). For the rare combined xeroderma pigmentosum (XP) and CS phenotype, all identified mutations are in three of the XP-associated genes, ERCC3 (XPB), ERCC2 (XPD), and ERCC5 (XPG). In a previous report, we identified several CS cases who did not have mutations in any of these genes. In this paper, we describe three CS individuals deficient in ERCC1 or ERCC4 (XPF). Remarkably, one of these individuals with XP complementation group F (XP-F) had clinical features of three different DNA-repair disorders--CS, XP, and Fanconi anemia (FA). Our results, together with those from Bogliolo et al., who describe XPF alterations resulting in FA alone, indicate a multifunctional role for XPF.

We describe a 59-year-old woman, with a history of autoimmune disease and disseminated uterine leiomyosarcoma, who developed a photoaggravated, blistering skin eruption. An initial rash, at the outset of treatment with chemo- and radiotherapy, resembled erythema multiforme. Review of the original skin biopsy showed it to be subacute cutaneous lupus erythematosus. There were no systemic symptoms or signs to suggest systemic lupus erythematosus. The much later photoaggravated rash consisted mainly of bullae and eventual epidermal denuding which resembled toxic epidermal necrolysis. We propose that the clinical and histological diagnosis is one of bullous subacute cutaneous lupus erythematosus in a patient with no other features of systemic lupus erythematosus.

Summary The expression of herpes varicella zoster virus in patients Already infected with the human immunodeficiency virus (HIV) provides the perfect illustration of an opportunist microbe at work. There is an increased incidence of herpes zoster which may be more sever, recurrent or disseminated. In both Likewise, varicella may be more severe and recurrent. In both patterns of infection a typical lesions in the form of persistent ulcerative or verrucous lesions have been seen. An HIV-positive patient is described who developed verrucous lesions de novo, 4 months after her child had varicella.

Anticonvulsants can cause a characteristic hypersensitivity reaction. This multisystem reaction typically presents as fever, mucocutaneous eruptions, lymphadenopathy and hepatitis. There is cross-reactivity between different anticonvulsants, which complicates subsequent therapy. We report three cases to illustrate both the typical features, and less common complications, of this under-recognized and life-threatening syndrome.

Castleman's lymphoma, a benign localized lymphoid hyperplasia, has been reported in association with POEMS syndrome, a multisystem reactive disorder that includes several skin manifestations. Benign reactive angioendotheliomatosis is a rare skin disorder that is associated with various systemic disorders. A patient with long-standing Castleman's lymphoma and POEMS syndrome also developed benign reactive angioendotheliomatosis.

Localized granuloma annulare is the commonest form of a granulomatous dermatosis characterized by flesh coloured or violaceous papules often arranged in rings. Several rare atypical variants are also reported including disseminated or generalized, subcutaneous and perforating types. There is a predilection for females and a documented association with diabetes mellitus in some cases. Recently it has been suggested that atypical variants of granuloma annulare might be associated with the acquired immunodeficiency syndrome (AIDS). We describe a patient presenting with extensive generalized granuloma annulare in whom an underlying diagnosis of Human Immunodeficiency Virus (HIV) disease was confirmed.

A study of 350 women with lichen sclerosus, originally made to elucidate the relationship between lichen sclerosus and autoimmunity, led to the amassing of a considerable amount of clinical material. Our review is confined to those with anogenital lesions (342), supplemented by some new cases (15), giving a total of 357 women with biopsy proven lichen sclerosus. It demonstrates the wide age range of the condition, the association with morphoea and lichen planus and the occurrence of squamous cell carcinoma in some cases. It also shows that inappropriate surgery has continued to be carried out for benign disease.

We report our experience, and review the literature, concerning 'intensive care dermatology'. Over a period of 14 months, 27 patients who had significant cutaneous problems were seen in the intensive care unit. These included primary dermatological conditions, multisystem disorders with cutaneous signs, complications of dermatological therapy, and skin conditions developing as complications of intensive care. We discuss the diagnosis and management of dermatological problems in the intensive care unit.

Summary We report the case of a homosexual male with a 5-year history of polyarthropathy and a 20-year history of a psoriasiform rash leading to the diagnosis of Reiter's disease and underlying HIV infection.

Summary Ichthyosis hystrix is a rare genodermatosis characterized by persistent spiny scales which cover a significant part of the skin surface. In many cases it is associated with palmoplantar keratoderma, and occasionally deafness and neurological defects coexist. The case of a man with ichthyosis hystrix is reported who developed skin malignancy and dysplastic keratoses, a complication which has not previously been recorded.

Summary Cutaneous malignant melanoma was diagnosed in three patients suffering from human immunodeficiency virus (HIV) infection. Staging at presentation inversely correlated with absolute CD4 count. In addition, a notably sparse lymphocytic inflammatory response to the melanoma was observed in two cases. Established data on melanoma in non-HIV immunosuppressed patients suggests a poor prognosis for melanoma in HIV disease.

Epidermal cell proliferation in psoriasis was studied after oral methotrexate using tritiated uridine. Psoriatic enteropathy has in the past been reported to reduce the absorption of methotrexate administered orally but this study showed that the onset of inhibition of mitosis and DNA synthesis occurred at the same time as after intramuscular administration of the drug. The cell kinetic data indicate that cells were blocked at the G1/S interface, and the kinetics of inhibition are discussed in terms of their implications for the mode of action of methotrexate in psoriasis. Considerable numbers of dead cells were seen in the epidermis from 6 to 24 h after oral methotrexate. The mode of action of methotrexate in psoriasis is currently unknown but whatever other actions it may have, any global hypothesis of its action will have to incorporate a flux to epidermal cell death.

Summary A 23-year-old woman is described with confluent yellowish-white papules and plaques on the face. This was associated with hyperplasia of sebaceous glands. There was no clinical evidence of seborrhoea or anhidrotic ectodermal dysplasia. This is considered to be a separate and distinctive clinical and pathological entity.

summary A study of autoimmune related phenomena in 350 women with histologically confirmed lichen sclerosus et atrophicus revealed that 21.5% had one or more autoimmune related diseases, 21% had one or more first degree relatives with an autoimmune-related disease, 42% had an autoantibody at a titre > 1:20, and 59.5% had one or more of these autoimmune-relateda phenomena. No statistically significant differences in the natural history of lichen sclerosus et atrophicus were demonstrated between those patients with autoimmune-related phenomena and those without.

In patients with moderate to severe inflammatory acne, complement (C3) was detected by immunofluorescence in sixteen early inflammatory acne lesions but in only one of thirteen biopsies of non-inflamed skin from acne sites. C3 deposition occurred particularly in the walls of small dermal blood vessels and at the dermo-epidermal junction. IgM was identified in vessel walls in four of sixteen early lesions. In eight late inflammatory lesions C3 deposition was much less prominent and was present in vessel walls in only two. None of the late lesions showed vascular deposition of IgM. The observations indicate that complement activation occurs in inflammatory acne and it is suggested that this may play a pathogenic role in the inflammation.

DNA flow cytometry was performed on formalin fixed, paraffin embedded melanocytic naevi. DNA aneuploidy was detected in all three types of naevus but was significantly more frequent in those naevi accepted as precursors of malignancy: that is, dysplastic and congenital pigmented hairy naevi. It may be that the presence of DNA aneuploidy has prognostic significance in these naevi. Technical problems were encountered in the analysis of data from melanocytic lesions so that caution is recommended in interpretation of studies using formalin fixed tissue.

Summary Three patients who developed toxic epidermal necrolysis whilst receiving carbamazepine are described. Two patients experienced severe oropharyngeal ulceration and extensive cutaneous necrolysis with subsequent transient alopecia, nail shedding and persistent ulceration of the tongue. Histology of the skin revealed changes resembling those found in not only erythema multiforme and toxic epidermal necrolysis but also homograft rejection and the acute graft-versus-host reaction, suggesting that cutaneous damage was mediated by ‘aggressor lymphocytes’ sensitized to epidermal cells.

SUMMARY Distinct aneuploid clones of keratinocytes were detected in six cases of cutaneous Bowen's disease. As Bowen's disease is an accepted precursor of malignancy, aneuploidy may prove to be a useful indicator of the risk of invasive change in dermatoses questionably pre-malignant.

SUMMARY Aneuploidy has not to date been demonstrated in any entirely benign condition and thus is held to be implicit of neoplasia. DNA flow cytometry can be used to detect DNA aneuploidy rapidly. A technique has been developed to make possible flow cytometric analysis of formalin-fixed skin. The technique was validated by study of benign and pre-malignant dermatoses. Further studies were performed on skin conditions of questionable malignant potential. DNA aneuploidy was demonstrated in lichen sclerosus et atrophicus. Flow cytometry was unable to distinguish keratoacanthomas from squamous cell carcinomas. Cells which contain an abnormal number of chromosomes are said to be aneuploid. They may contain less DNA than the normal so-called ‘diploid’ cells and these are called‘hypodiploid'. They may contain more DNA and are then called‘hyperdiploid'. The DNA status is best expressed as the DNA index. This figure indicates the quantity of DNA in the aneuploid cells in relation to that in normal diploid cells. A DNA index of 1.0 would therefore signify the presence of only diploid cells and an index of 1.9 would indicate almost tetraploid aneuploid cells. Aneuploidy is common in tumours. DNA aneuploidy, the presence of abnormal quantities of DNA detected by flow cytometry (FCM), is presumptive of aneuploidy and has been demonstrated in 80–90% of solid tumours.1 In our laboratory DNA aneuploidy has been demonstrated by FCM in 70% of 399 solid tumours. It has also been seen in a number of pre-malignant conditions such as chronic atrophic gastritis.2 Except for tetraploid stemlines, normal or reactive tissue is not associated with aneuploidy.1 Aneuploidy is thus held to be implicit of neoplasia.3 It was decided to investigate the significance of DNA aneuploidy in skin disease to determine if indeed DNA aneuploidy is specific to malignant and pre-malignant dermatoses and to determine if detection of DNA aneuploidy could be used to predict the outcome in conditions of debateable pre-malignancy.

SUMMARY Primary cutaneous amyloidosis is uncommon in Europeans. A British family is described in which an extremely rare variant was inherited as an autosomal dominant. The subtlety of physical signs in this family contrasted with the severity of the associated pruritus. Transepidermal elimination of amyloid was a characteristic histological feature.

A patient with impaired renal function following aortic valve replacement developed prolonged neuromuscular paralysis during treatment with tubocurarine, gentamicin and lignocaine but recovered after peritoneal dialysis. The potential neuromuscular blocking properties of these three drugs are discussed.

Summary Widespread thrombophlebitis was the presenting feature of sarcoidosis in a 29-year-old West African woman. To our knowledge superficial thrombophlebitis has not previously been reported in sarcoidosis. Superficial thrombophlebitis is classically linked with pancreatic adenocarcinoma. It has also been associated with many other neoplasms as well as collagen vascular diseases, Behget's syndrome, lymphoproliferative diseases and several infections, such as typhoid or rickettsiosis (Ryan & Wilkinson, 1979). As far as we are aware, widespread superficial thrombophlebitis has not been previously seen with sarcoidosis and we describe a case in which it was a major feature of the disease.