Recognition of the phenotype of thalidomide embryopathy in countries endemic for leprosy

Abstract

Thalidomide is the best-known teratogen worldwide. It was first marketed as a sedative in the late 1950s, but the birth of ~10 000 children with birth defects resulted in the withdrawal of thalidomide from the market in 1962. Thalidomide embryopathy affects almost all organs but the main defects are concentrated in the limbs, eyes, ears, and heart. Shortly after the withdrawal of thalidomide from the market, its effectiveness in the treatment of erythema nodosum leprosum, an inflammatory condition resulting from leprosy, was reported and since the mid-1990s, the drug has been used widely in the treatment of cancers and autoimmune diseases, among other conditions. 40 000 new cases of leprosy are diagnosed every year in Brazil. Although there is a strict legislation for the prescription and use of thalidomide in Brazil, cases of thalidomide embryopathy have continued to be reported. Here, we present two new cases of thalidomide embryopathy identified in 2011 and review the major clinical findings in the literature that can aid the identification of the embryopathy.

Zika Fetal Neuropathogenesis: Etiology of a Viral Syndrome

“…The characteristic presentation of Zika congenital syndrome ranges from viral centric (microcephaly, blindness, ventricular calcifications, and fetal presence of ZIKV by rt-PCR) to another extreme (long bone dysgenesis, negative for ZIKV) possibly associated with placental insufficiency. Epidemiological assessment of potential confounding risk factors for Zika congenital syndrome—including preceding immunologically cross-reactive arboviral infection [7,18,19]—and potential thalidomide sharing by patients being treated for leprosy [27–30] remains to be completed. To underscore the point, leprosy is now endemic throughout much of Brazil, including Pernambuco [235], and postexposure prophylaxis of exposed individuals has been advocated [236,237].…”

“…Investigation soon revealed a correlation between ZIKV infection and the unusually high rate of infant microcephaly observed at the heart of the outbreak in Recife, Pernambuco. The striking features of ZIKV fetal syndrome may have gone unrecognized during prior outbreaks in the Pacific islands or may involve regional confounding variables or risk cofactors present in Brazil, such as prior exposure to dengue virus (DENV) [18,19], genomic changes in regionally circulating ZIKV [20–23], immunologic naivety and vaccination status of local populations [24,25], and exposure to pyriproxifen-containing insecticides [26] or thalidomide [27–30]. The current pathology may also be consequent to recent viral mutations, such as observed changes in the prM protein of the Brazilian ZIKV strains [11,31,32].…”

Pomalidomide is nonteratogenic in chicken and zebrafish embryos and nonneurotoxic in vitro

“…However, long-term use of Thalidomide in adult patients can result in detrimental side effects, such as peripheral neuropathy (4,5), and carries the risk of inducing birth defects. Indeed, despite careful controls on Thalidomide use and distribution, a large number of babies with Thalidomide embryopathy have been born in the last two decades in Brazil where it is administered mainly for the treatment of leprosy and its complications (6,7). Consequently, there is intense interest in developing a more potent anti-inflammatory form of Thalidomide with enhanced clinical benefit, but fewer side effects.…”

[No Title Available]

“…The environmental disorder is thalidomide embryopathy, resulting from a drug used for the treatment of leprosy in endemic areas of Brazil (Vianna et al , 2013). Autosomal recessive disorders were the most prevalent rumors [0.534 per million inhabitants (CI: 0.435–0.647)] and clusters [0.300 per million inhabitants (CI: 0.228–0.388)] compared with the remaining etiologic groups: autosomal dominant, X-linked, multifactorial, environmental, and unspecified etiology (Table 2).…”