Aileen Taylor

Mutations in ABCA12 underlie the severe congenital skin disease harlequin ichthyosis

Harlequin ichthyosis (HI) is the most severe and frequently lethal form of recessive congenital ichthyosis. Although defects in lipid transport, protein phosphatase activity, and differentiation have been described, the genetic basis underlying the clinical and cellular phenotypes of HI has yet to be determined. By use of single-nucleotide-polymorphism chip technology and homozygosity mapping, a common region of homozygosity was observed in five patients with HI in the chromosomal region 2q35. Sequencing of the ABCA12 gene, which maps within the minimal region defined by homozygosity mapping, revealed disease-associated mutations, including large intragenic deletions and frameshift deletions in 11 of the 12 screened individuals with HI. Since HI epidermis displays abnormal lamellar granule formation, ABCA12 may play a critical role in the formation of lamellar granules and the discharge of lipids into the intercellular spaces, which would explain the epidermal barrier defect seen in this disorder. This finding paves the way for early prenatal diagnosis. In addition, functional studies of ABCA12 will lead to a better understanding of epidermal differentiation and barrier formation.

Harlequin ichthyosis: a review of clinical and molecular findings in 45 cases.

OBJECTIVEnTo assess the clinical outcomes of 45 cases of harlequin ichthyosis and review the underlying ABCA12 gene mutations in these patients.nnnDESIGNnMulticenter, retrospective, questionnaire-based survey.nnnSETTINGnDermatology research institute.nnnPARTICIPANTSnPatients with harlequin ichthyosis for whom we had performed ABCA12 mutation analysis.nnnMAIN OUTCOME MEASURESnReferring physicians were asked to complete a questionnaire using the patients notes, detailing the clinical outcome of the affected child. In each case, the causative ABCA12 mutation was identified using standard polymerase chain reaction and sequencing techniques.nnnRESULTSnOf the 45 cases, the ages of the survivors ranged from 10 months to 25 years, with an overall survival rate of 56%. Death usually occurred in the first 3 months and was attributed to sepsis and/or respiratory failure in 75% of cases. The early introduction of oral retinoids may improve survival, since 83% of those treated survived, whereas 76% who were not given retinoids died. Recurrent skin infections in infancy affected one-third of patients. Problems maintaining weight affected 44%. Three children developed an inflammatory arthritis, and developmental delay was reported in 32%. Mutation analysis revealed that 52% of survivors had compound heterozygous mutations, whereas all deaths were associated with homozygous mutations.nnnCONCLUSIONSnHarlequin ichthyosis should be regarded as a severe chronic disease that is not invariably fatal. With improved neonatal care and probably the early introduction of oral retinoids, the number of survivors is increasing. Compound heterozygotes appear to have a survival advantage.

Sebaceous hyperplasia in organ transplant recipients: Shared aspects of hyperplastic and dysplastic processes?

BACKGROUNDnPatients receiving kidney or heart transplants are subject to a wide range of cutaneous changes attributed largely to the immunosuppression required to prevent rejection of their transplant. In addition to infection, they have an increased incidence of dysplastic lesions, some of which are malignant.nnnOBJECTIVEnOur purpose was to determine the incidence of sebaceous hyperplasia in heart and kidney transplant recipients and its association with neoplasia.nnnMETHODSnPatients undergoing heart transplantation from a single transplant center were examined during a 30-month screening period to establish the prevalence of cutaneous abnormalities.nnnRESULTSnSixteen of 104 (16%) heart transplant recipients had sebaceous hyperplasia in comparison with 1% of an age- and sex-matched control group. Those with sebaceous hyperplasia did not have a significantly higher incidence of hypertrichosis than those without sebaceous hyperplasia.nnnCONCLUSIONnSebaceous hyperplasia is seen in heart transplant recipients. It does not appear to be connected with hypertrichosis, in which it is believed that the pilosebaceous unit is the target of the direct effect of cyclosporine. We propose that the development of sebaceous hyperplasia is related to the process of dysplastic epithelial proliferation in transplant recipients.

Pityriasis lichenoides: the differences between children and adults

Backgroundu2002 Pityriasis lichenoides (PL) is a skin disease that affects both children and adults. Anecdotally, it is said to run a more benign course in children, with a frequent tendency to self‐resolution. However, to our knowledge, there have been no published studies comparing PL in both age groups.

Narrowband ultraviolet B phototherapy in children with moderate-to-severe eczema: a comparative cohort study†

There is only retrospective evidence for the efficacy of narrowband ultraviolet B (NB‐UVB) in children with eczema.

Idiopathic Infantile Pyoderma Gangrenosum with Stridor Responsive to Infliximab

Abstract:u2003 A 4‐month‐old female infant presented with widespread pyoderma gangrenosum associated with stridor, presumed secondary to tracheal involvement. No underlying cause was revealed despite extensive investigation. Treatment with immunosuppressive agents only partially suppressed disease activity. Complete resolution followed treatment with infliximab. We review this rare condition in infants and discuss treatment with infliximab not previously described in this age group.

Comparison of cadexomer iodine and dextranomer for chronic venous ulcers

Forty‐two patients with chronic resistant varicose ulcers were observed for 6 weeks on standard out‐patient therapy, and then randomly allocated to daily treatment with either cadexomer iodine (CI), a new topical agent, or dextranomer for a further 6 weeks, at which time ulcers judged clinically not to be responding could be changed to the other treatment for the remaining 20 weeks of the trial. There was no significant reduction in ulcer area during the first 6 weeks on CI or dextranomer. A significant preference for CI was shown by the optional crossover. Retrospective analysis of ulcer size shows this was not related to severity and preference was probably due to bias towards the new treatment, the trial not being blind. Neither therapy significantly reduced colonization by β‐haemolytic Streptococcus, Staphytocoaus aureus, Pseudomonas or Proteus. The discrepancy between these and previous findings with CI is largely due to different methods of analysis rather than different results. We conclude that, in chronic resistant venous ulcers, topical therapy is of little importance compared with measures which improve tissue oxygenation and repair.

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

Oral propranolol is widely prescribed as first‐line treatment for infantile haemangiomas (IHs). Anecdotally, prescribing practice differs widely between centres.

United Kingdom survey of current management of juvenile localized scleroderma

OBJECTIVESnJuvenile localized scleroderma (JLS) is a rare condition that is often difficult to assess and for which a variety of monitoring tools have been described. We aimed to describe how monitoring tools are used and perceived by clinicians in the UK, to ascertain treatments used for JLS and to provide a description of transition arrangements to adult care.nnnMETHODSnAn e-survey of UK paediatric rheumatologists and dermatologists managing children and young people (CYP) with JLS was distributed using the national organisations representing these clinician groups. We asked respondents for their views and experience using 15 JLS monitoring tools, about transition services and about treatments used.nnnRESULTSnThirty-five dermatologists and 13 paediatric rheumatologists responded. Paediatric rheumatologists managed more CYP with JLS than dermatologists (median 16-20 and 3, respectively). Transition arrangements were reported by 43% of dermatologists and 91% of paediatric rheumatologists. Medical photography was the most frequently regularly used monitoring tool (73% respondents). The modified Rodnan skin score was the skin score used most commonly: 33% of paediatric rheumatologists and 3% of dermatologists reported using this tool frequently. Topical treatments and ultraviolet light were used by 49-80% of dermatologists and 0-8% paediatric rheumatologists. Biologic drugs and CYC were used by 0-3% of dermatologists and 31-46% of paediatric rheumatologists.nnnCONCLUSIONnHow monitoring tools are accessed, used and perceived by paediatric rheumatologists and dermatologists in the UK varies between and within clinician groups, as do treatment prescribing patterns and transition arrangements. These differences will impact on the feasibility of conducting multicentre clinical trials and on standardising clinical care.

Hereditary woolly hair with ocular involvement

A case of hereditary woolly hair associated with Coats’ disease of the eyes, a rare type of exudative retinitis, is reported.