Digital clubbing is the most prominent feature in primary (PHO) and secondary (pulmonary) hypertrophic osteoarthropathy (HO). Homozygous and compound heterozygous germline mutations in the 15-hydroxyprostaglandin dehydrogenase (HPGD) gene encoding the major prostaglandin PGE2 catabolizing enzyme have been recently described in familial PHO cases. Elevated prostaglandin levels in affected individuals with cytokine-mediated tissue remodelling and vascular stimulation may underlie PHO and associated features as hyperhidrosis, acroosteolysis, pachyderma, periostosis and arthritis. We present clinical and biochemical data of three unrelated PHO families with HPGD mutations. The truncating mutation c.175_176del was found in two of our families and in one of the recently described pedigrees, all of European origin. We present evidence that c.175_176del is a recurrent mutation rather than an ancient founder allele. Two novel heterozygous HPGD mutations, the nonsense mutation c.118G>T (p.Glu40X) and the missense mutation c.563C>T (p.Thr188Ile), could be identified in a third family. We postulate that all HPGD mutations constitute loss-of-function alleles due to protein truncation or missense changes that affect hydrogen bonds lining the 15-PGDH enzyme reaction cavity. Elevated prostaglandin levels may give rise to use of non-steroidal anti-inflammatory drugs; however, therapeutic strategies have not been reported to date. Naproxen treatment in one of our mutation-positive patients resulted in alleviation of pain caused by periostosis and arthritis as well as reduction in substantially elevated prostaglandin levels, while no significant effects on digital clubbing, hyperhidrosis and pachyderma were observed. Further experience with nonsteroidal anti-inflammatory drugs in PHO is awaited.

SummaryVoriconazole is a second-generation triazole antifungal approved for the treatment of invasive fungal infections, particularly with Aspergillus, Candida, Fusarium, and Scedosporium spp. Frequently reported adverse effects of voriconazole include visual disturbance (21 %), elevated liver enzymes (15.6 %) and rashes (7 %), which are largely attributable to drug-induced photosensitivity. We report a case of serious phototoxicity in a 8 year old boy who underwent chemotherapy for AML. He received voriconazole for the treatment and subsequent re-infection prophylaxis after pulmonary aspergillosis. One year after the start of therapy he developed blistering eruptions on his face after minimal sunlight exposure. Recent reports about the development of squamous cell carcinoma and melanoma, respectively, in children during and after oral therapy with voriconazole seem to warrant systematic follow-up investigations of all voriconazole-treated patients.

Lichen planus is a chronic inflammatory disease of the skin and mucous membranes. Typically, skin lesions include violaceous, polygonal, flat papules and plaques. However, the clinical presentation of lichen planus can be heterogeneous and show divergent degrees of cutaneous and mucous manifestation. The disease usually affects adults and is only rarely encountered in children. Here, we present a 7-year-old boy who rapidly developed itching skin lesions on the extremities and trunk. He had no history of concomitant drug intake, infection or vaccination. Clinical examination of the skin found multiple white-grayish papules and plaques whereas the scalp, mucous membranes and nails were not affected. Histologic examination showed typical findings of lichen planus. We initiated topical corticosteroid therapy, which resulted in healing of the skin lesions within 4 weeks. To our knowledge this is the first instance of exanthematous lichen planus in childhood successfully treated with topical corticosteroid ointment alone. Thus, even generalized lichen planus lesions can be effectively cleared without systemic therapies, which can be potentially associated with serious side effects, especially in children.

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Orally active kinase inhibitors such as Sorafenib are known to elicit cutaneous side effects in the majority of adult patients, whereas specific cutaneous complications of this agent have not been described in children so far. We here present the first pediatric case of Sorafenib-induced hand-foot-skin reaction and its successful topical therapy facilitating continuation of kinase inhibitor treatment.