Adam S. Geyer

Bullous pyoderma gangrenosum as the presenting sign of fatal acute myelogenous leukemia

Bullous pyoderma gangrenosum begins as a bulla, nodule or nonulcerated erythematous plaque that blisters or ulcerates to form a superficial ulcer surrounded by a hemorrhagic, bullous border, which is surrounded by a blue–gray halo. Bullous pyoderma gangrenosum is most commonly associated with hematologic malignancies, specifically, acute myelogenous leukemia (AML). We report a patient whose initial presentation with bullous pyoderma gangrenosum prompted the appropriate diagnostic evaluation and confirmation of AML, which was ultimately fatal. We emphasize that a thorough hematologic investigation, including bone marrow biopsy, should be performed in all patients who present with lesions clinically suggestive of bullous pyoderma gangrenosum because the skin lesion may be the only indicator of the underlying hematologic disorder.

Cutis Verticis Gyrata in a Patient with Noonan Syndrome

Abstract:  We report cutis verticis gyrata in a patient with Noonan syndrome. While cutis vertices gyrata has been shown to have a strong association with chromosomal abnormalities, especially Turner syndrome, this infant represents only the second reported instance of cutis verticis gyrata occurring in a patient with Noonan syndrome.

Netherton Syndrome with Extensive Skin Peeling and Failure to Thrive due to a Homozygous Frameshift Mutation in SPINK5

Background: Netherton syndrome (NTS) is a rare autosomal recessive multisystem disorder characterized by congenital erythroderma and ichthyosis, hair shaft abnormalities and immune dysregulation. The disorder is caused by deleterious mutations in the SPINK5 gene, encoding the serine protease inhibitor LEKTI. Objective: Our objective was to investigate if the erythrodermic variant of peeling skin syndrome is also caused by SPINK5 mutations and to study the consequences of the disease on infantile brain development. Methods: In an infant with extensive erythroderma, peeling skin and failure to thrive, we analyzed the SPINK5 gene for pathogenic mutations by direct DNA sequencing and performed repeated brain MRI studies with diffusion-weighted imaging. Results: We identified a homozygous 4-base-pair insertion in exon 5 of SPINK5, which introduces a premature termination codon and appears to be a common mutation among West Indies islanders. MRI analyses revealed a persistent diffuse volume loss. Conclusion: Our results confirm that early truncation mutations of the coding sequence of SPINK5 produce a severe phenotype and that generalized peeling skin is one of the manifestations of NTS. We further demonstrate for the first time that NTS may be associated with MRI abnormalities indicative of a permanent tissue injury of the brain.

Drugs and nails

In this issue, Ghetti et al . report on the occurrence of onycholysis and subungual haemorrhages after paclitaxel therapy. This report adds to the ever-increasing list of cancer chemotherapeutic agents that are associated with certain nail abnormalities. Obviously, it is important for clinicians to recognize specific drug-induced side-effects. However, these reports may also provide us with molecular agents that can be used to analyse and dissect the homeostatic mechanisms that control the nail unit. Drug-induced nail abnormalities are characterized by the frequent involvement of all 20 nails, a temporal correlation with drug intake, and the usual disappearance upon cessation of the offending drug. 1 Toenails may seem to be less affected, but this is probably due to the slower growth rates of these nails. Most commonly, the drug has a direct toxic effect on one of the components of the nail apparatus. Depending on which nail component(s) (nail matrix, bed, folds, plate (secondary to matrix involvement) or hyponychium) is affected, a variety of nail changes may be observed. 2 For instance, drug toxicity to nail matrix keratinocytes may result in Beau’s lines, onychomadesis, leuconychia, nail plate abnormalities such as brittle and thin nails, and decreased or increased nail growth rates. By contrast, drug toxicity to nail bed keratinocytes may result in onycholysis and pseudo-leuconychia. Nail abnormalities can also depend on the cell type that is affected. Many of the drug-induced nail pigmentation changes are the result of increased melanin production by nail matrix melanocytes. On occasion, the nail abnormalities are secondary to drug-induced toxicities outside the nail unit. For instance, splinter haemorrhages and subungual haematoma can be caused by vascular damage or impaired perfusion of the nail bed. Cancer chemotherapeutic agents often induce nail changes, and nail pigmentation is probably the most frequently observed nail abnormality. 3 The mechanism of drug-induced hyperpigmentation is not fully understood, but this is most probably due to increased melanogenesis in matrix melanocytes. Different patterns of hyperpigmentation such as longitudinal bands, transverse bands and diffuse darkening have been described after the administration of many different cancer chemotherapeutic drugs. Beau’s lines, transverse leuconychia and onychomedesis are the result of nail matrix toxicity, and can be seen after intensive or combined chemotherapy. Nail bed toxicity, as manifested in apparent leuconychia or onycholysis, may be seen in association with nail bed haemorrhage, which may be exacerbated by concurrent thrombocytopaenia. Acute paronychia has also been described after treatment with methotrexate. 4