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Monofocal outer retinitis associated with hand, foot, and mouth disease caused by coxsackievirus.

PURPOSE: To report symptoms and signs from an otherwise healthy man with photopsia and monofocal outer retinitis occurring 3 days after the onset of hand, foot, and mouth disease. METHOD: Case report. RESULTS: Ophthalmic examination revealed a single circumscribed area of pigment epithelial mottling in the left eye and a corresponding nonarcuate absolute scotoma. Fluorescein angiography demonstrated attenuation of the retinal pigment epithelium. Serologic tests at 1 month after the onset disclosed serum antibody to enterovirus. CONCLUSION: The close association between the cutaneous eruption and the onset of visual symptoms suggests that the retinal lesion was caused by coxsackievirus infection.

Adult↗

Properties of virus isolated from an epidemic of hand-foot-and-mouth disease in 1973 in the city of Matsue. Comparison with Coxsackievirus group A type 16 prototype.

The virus strains isolated from clinical cases in an epidemic of hand-foot-and-mouth disease in Matsue in 1973 were characterized and its properties were compared with those of the Coxsackievirus group A type 16 (CA 16) prototype strain. The virus isolated in 1973 was similar to CA16 prototype virus with respect to morphology in electron microscopy, resistance to ether and capability to replicate in meidum containing fluorodeoxyuridine. Cross neutralization tests using guinea-pig and horse antisera revealed that there was little or no detectable common antigen between the two viruses. The two viruses also differed in heat stability of virion infectivity: the 1973-viruses were much more resistant to heat than the prototype virus. Under one-step growth conditions in Vero cell cultures, growth rate and virus yield of the 1973-viruses were lower than those of CA16, but this property was independent of incubation temperatures, pH of culture medium and other culture conditions. Several other differences in property between the 2 strains are also described. It is concluded that the epidemic in 1973 was caused by a virus whose properties differed greatly from those of the CA16 prototype.

Animals↗

Structural proteins of hand, foot and mouth disease viruses.

Coxsackievirus A16 (CA16) and enterovirus 71 (E71), which cause hand, foot and mouth disease, were compared with respect to their polypeptide composition by PAGE. Only three proteins were resolved for CA16, whereas the four characteristic structural proteins of E71, (VP1, VP2, VP3 and VP4) were separated. The distribution of labeled proteins suggested that the molecular weights of VP2 and VP3 of CA16 were very similar. The smallest protein, VP4, of CA16 and E71 had the same molecular weight, but the other proteins of the two serotypes were different in their molecular weights.

Electrophoresis, Polyacrylamide Gel↗

Update on a family with hand-foot-genital syndrome: hypospadias and urinary tract abnormalities in two boys from the fourth generation.

We describe a fourth generation of involvement with hand-foot-genital syndrome. The first 3 generations of this family, which included 5 affected females and no affected males, were reported previously by Verp et al. [1983]. In the fourth generation, 2 affected males are identified. To our knowledge, the findings of bilateral vesicoureteral reflux in one boy and bilateral ureteropelvic junction obstruction in his cousin represent the first reports of urinary tract abnormalities in males with this syndrome.

Adult↗

Usefulness of low-level laser for control of painful stomatitis in patients with hand-foot-and-mouth disease.

OBJECTIVE: The aim of this study was to evaluate the usefulness of low-level laser therapy (LLLT) for the control of painful stomatitis in patients with hand-foot-and-mouth disease (HFMD). BACKGROUND DATA: LLLT has been successfully applied to various painful oral mucosal diseases, although there have been few reports on LLLT for HFMD patients. MATERIALS AND METHODS: Through a randomized double-blind placebo controlled trial, the painful period of HFMD stomatitis was compared between the LLLT group (n=11) and the placebo LLLT one (n=9), which had similar clinical backgrounds. The LLLT parameters supplied were as follows: wavelength of 830 nm, power of 30 mW, frequency of 30 Hz, and energy output of 1.1 J/cm2. Acceptability and safety of the treatment were also evaluated. RESULTS: The painful period was shorter in the LLLT group (4.0 +/- 1.3 days) than in the placebo LLLT one (6.7 +/- 1.6 days) with a statistically significant difference (p<0.005). The treatment was judged acceptable for 90.0% (18 of 20) of patients. No adverse events were observed in any cases. CONCLUSION: LLLT is a useful method to control HFMD stomatitis by shortening the painful period, with its high acceptability and lack of adverse events.

Child↗

Heritability and linkage analysis of hand, foot, and eye preference in Mexican Americans.

Functional lateralities are of interest due to their relationship with cerebral lateralisation and language development. However, genes influencing sidedness remain elusive. We measured direction and consistency of hand, foot, and eye preference in 584 Mexican-Americans from families participating in the San Antonio Family Diabetes/Gallbladder Study. Using maximum-likelihood-based variance components methods, we estimated weak (.11 <or= h2<or=.17) but significant heritability for foot preference, eye preference, several hand preferences (writing, drawing, throwing, using scissors, using spoon, striking match), and a composite hand preference trait. Self-reported handedness was significantly heritable (h2=.57), whereas hand preference for opening a box or using a toothbrush or knife was not. Many trait pairs had significant genetic correlations, and all had significant environmental correlations. Using genome-wide multipoint linkage screens using 382 highly informative autosomal STR markers, we identified suggestive linkage signals for drawing (LOD 2.10) and writing (LOD 2.00) hand preference on chromosome 12q21-23, in the region flanked by markers D12S1300 and PAH. A suggestive signal (LOD 2.46) for eye preference occurred on chromosome 22pter, near marker D22S420. No obvious candidate genes occur in these regions. Our results indicate that genes are an important component of side preferences, and suggest chromosomal regions for further investigation.

Choice Behavior↗

[The hand-foot-uterus syndrome. A report of a case with recessive autosomal inheritance].

The authors report a new case of hand-foot-uterus syndrome, an infrequent and peculiar clinical condition characterized by skeletal anomalies of the extremities associated with alterations in the development of Mullerian derivation structures. The female patient in fact present morphological and skeletal anomalies to the extremities and a bicornate, twin-necked uterus with double vagina. This genetic condition is normally transmitted with a autosomal dominant pattern. The consanguinity of the parents and the absence of other like cases in the family led the authors to suppose that this is an even rarer form with a recessive autosomic-type inheritance. The importance of an accurate diagnosis is underlined not only to ensure better management, but above all for a more appropriate examination of their reproductivity.

Abnormalities, Multiple↗

Fluorescent antibody responses of cases and contacts of hand, foot, and mouth disease.

Paired sera from clinical cases, familial contacts, and school contacts of hand, foot, and mouth disease were tested by indirect immunofluorescence against a strain of coxsackie A16 virus which had been adapted to human fibroblast tissue-cultured cells. All of the 22 clinical cases developed immunoglobulin (Ig) G antibodies, and 11 responded with IgM and 10 with IgA antibodies. Seventeen of 21 familial contacts of cases showed subclinical infection as determined by development of IgG antibodies. Only seven and nine, respectively, of these had demonstrable IgM and IgA antibodies. Thirteen of 16 school classmates of three clinical cases were shown to have experienced subclinical infection by the development of IgG antibodies. Only five had antibodies in the IgM fraction, and three had antibodies in the IgA fraction. A comparison of IgG titers with those obtained by neutralization tests provides further evidence that the indirect fluorescent antibody technique represents a rapid diagnostic procedure for this disease.

Adolescent↗

Seasonal models of herpangina and hand-foot-mouth disease to simulate annual fluctuations in urban warming in Tokyo.

In order to investigate the effects of global warming, we attempted to establish seasonal models to predict fluctuations in rates of herpangina (HA) and hand-foot-mouth disease (HFMD) associated with weather conditions and calendar months in Tokyo, Japan. Surveillance data tracking HA/HFMD incidences in Tokyo was retrieved from the Infectious Agents Surveillance Report, published by the National Institute of Infectious Diseases in Japan. From the Meteorological Agency, we obtained data for 54 weather condition parameters. The annual fluctuations in reported HA cases comprising start, peak, and end weeks almost exactly matched the model, although peak levels for each fluctuation did not always match in HFMD. Furthermore, for the HA model, 88% of the variations among observed HA cases were explained by the linear relationship with the seasonal parameters investigated, which was higher than the 64% observed for the HFMD model. The HA and HFMD models were applied to data from the years 1999 to 2002, and demonstrated correlations of 86% and 64%, respectively. These models predicted that warmer climate conditions would lead to an increased number of HA and HFMD cases. These results suggest that our seasonal models may quantify the dependency of infectious diseases on seasonal parameters and simulate the impact of global warming.

Child↗

Adenovirus type 21-associated acute flaccid paralysis during an outbreak of hand-foot-and-mouth disease in Sarawak, Malaysia.

We report the virological and clinical features of 8 children who presented with adenovirus-associated acute flaccid paralysis (AFP) during an epidemic of enterovirus type 71 (EV71)-associated hand-foot-and-mouth disease (HFMD) in Sarawak, Malaysia, in 1997. Neutralization tests and phylogenetic analysis revealed adenovirus type 21 (Ad21), although DNA restriction digests suggested that this virus was different from the prototype Ad21. Four children had upper-limb monoparesis, 2 had lower-limb monoparesis (one of whom had changes in the anterior spinal cord noted on magnetic resonance imaging), and 2 had flaccid paraparesis. At follow-up, 4 children were noted to have made full recoveries and 3 had residual flaccid weakness and wasting. Neurophysiological investigation revealed a mixture of axonal and demyelinating features in motor and sensory nerves, with denervation. These findings suggest that Ad21 might cause AFP by anterior horn cell damage or neuropathy of the brachial or lumbosacral plexus. The occurrence of these unusual adenovirus infections during an outbreak of EV71-associated HFMD suggests that an interaction between the 2 viruses may have occurred.

Acute Disease↗

Identification of enterovirus 71 isolates from an outbreak of hand, foot and mouth disease (HFMD) with fatal cases of encephalomyelitis in Malaysia.

Thirteen enterovirus 71 (EV71) isolates were obtained from both fatal and non-fatal infections of patients seen in Peninsula Malaysia and in Sarawak during an outbreak of hand, foot and mouth disease (HFMD) in Malaysia in 1997, with incidences of fatal brainstem encephalomyelitis. The isolates were identified using immunofluorescence staining, neutralization assays, and partial sequencing of the 5' untranslated regions (UTR). Assessment of the potential genetic relationships of the isolates using the partial 5'UTR sequences suggested clustering of the isolates into at least two main clusters. Isolates from Peninsula Malaysia were found in both clusters whereas Sarawak-derived isolates clustered only in cluster II. Isolates derived from fatal infections, however, occurred in both clusters and no distinctive nucleotide sequences could be attributed to the fatal isolates. Examination of the nucleotide sequences revealed at least 13 nucleotide positions in all the isolates which differ completely from the previously reported EV71 5'UTR sequences. In addition, at least 11 nucleotide position differences within the 5'UTR were noted which differentiated cluster I from cluster II. Predicted secondary RNA structures drawn using the nucleotide sequences also suggested differences between isolates from the two clusters. These findings suggest the presence of at least two potentially virulent EV71 co-circulating in Malaysia during the 1997 HFMD outbreak.

5' Untranslated Regions↗

Hand-foot-and-mouth disease: report of a case in Texas.

Coxsackie virus infections are highly contagious and can occur at epidemic levels within low socioeconomic populations. Since these diseases spread by contact, summer and fall occurrences increase significantly. A low grade fever and malaise are often related to non-specific viral infections. Hand-foot-and mouth disease (HFMD) is specifically caused by coxsackie virus.

Child, Preschool↗

Hand-foot syndrome in a patient with multiple fire ant stings.

The case is reported of an elderly patient with known previous exposure to fire ant stings, and who presented with hand-foot syndrome (HFS) in the setting of multiple fire ant stings to the lower extremities. Both hands and both feet were red, swollen, and mildly tender. Treatment was with fluocinonide cream, and all symptoms resolved as the classic fire ant skin lesions regressed. HFS was initially reported in association with acute crisis in sickle cell anemia and thalassemia and more recently as a common toxicity of chemotherapy administration. This is the first report of its occurrence in the setting of fire ant envenomization. Although recent literature may indicate a potential therapeutic benefit from COX-2 antagonists, the process appears to be self-limited, and requires only conservative treatment.

Aged↗

Incidence and severity of hand-foot syndrome in colorectal cancer patients treated with capecitabine: a single-institution experience.

BACKGROUND: Hand-foot syndrome (HFS) has been previously reported as a side effect in 45-56% of patients treated with capecitabine. However, the natural history of HFS has not been fully characterized. In this study, we investigate the incidence, severity, and time course of HFS. DESIGN: Toxicity data collected for 41 patients treated in two clinical trials were analyzedfor the occurrence of HFS. Proportions of patients developing HFS after capecitabine treatment were calculated, and the severity and time course of HFS were analyzed. RESULTS: Twenty-eight (68.3%) of the 41 patients had at least one episode of HFS. Most patients had their first (92.9%) or most severe (67.9%) episode of HFS within the first two cycles of treatment. Eighty-nine percent of the HFS episodes were grade 1 or 2; only 11% were grade 3. CONCLUSIONS: HFS is common in patients treated with capecitabine, and usually starts within the first two cycles of therapy.

Adenocarcinoma↗

Deaths of children during an outbreak of hand, foot, and mouth disease in sarawak, malaysia: clinical and pathological characteristics of the disease. For the Outbreak Study Group.

From April through June 1997, 29 previously healthy children aged <6 years (median, 1.5 years) in Sarawak, Malaysia, died of rapidly progressive cardiorespiratory failure during an outbreak of hand, foot, and mouth disease caused primarily by enterovirus 71 (EV71). The case children were hospitalized after a short illness (median duration, 2 days) that usually included fever (in 100% of case children), oral ulcers (66%), and extremity rashes (62%). The illness rapidly progressed to include seizures (28%), flaccid limb weakness (17%), or cardiopulmonary symptoms (of 24 children, 17 had chest radiographs showing pulmonary edema, and 24 had echocardiograms showing left ventricular dysfunction), resulting in cardiopulmonary arrest soon after hospitalization (median time, 9 h). Cardiac tissue from 10 patients showed normal myocardium, but central nervous system tissue from 5 patients showed inflammatory changes. Brain-stem specimens from 2 patients were available, and both specimens showed extensive neuronal degeneration, inflammation, and necrosis, suggesting that a central nervous system infection was responsible for the disease, with the cardiopulmonary dysfunction being neurogenic in origin. EV71 and possibly an adenovirus, other enteroviruses, or unknown cofactors are likely responsible for this rapidly fatal disease.

Antigens, Viral↗

Hand-foot syndrome variant in a dihydropyrimidine dehydrogenase-deficient patient treated with capecitabine.

We present a case with dihydropyrimidine dehydrogenase (DPD) deficiency that manifested a variant of hand-foot syndrome (HFS). A 52-year-old man received capecitabine for adjuvant treatment of rectal cancer. On the ninth day of the first cycle, he presented to the clinic with a rash on the dorsum of both hands accompanied by symptoms of pain, erythema, swelling, and desquamation consistent with grade 3 HFS. The palms of his hands and soles of his feet were only tender with no apparent rash or discoloration. Dihydropyrimidine dehydrogenase activity was evaluated by radio assay using peripheral blood mononuclear cells. Dihydropyrimidine dehydrogenase activity was below normal: 0.12 nmol/minute/mg protein. Capecitabine was not resumed, and the rash resolved in 3 weeks with the use of pyridoxine and Udderly Smooth balm. Interestingly, HFS is rarely seen with 5-fluorouracil regimens containing selective DPD-inhibitors. This patient with DPD deficiency manifested a variant of HFS. The pharmacologic basis for the development of HFS in DPD-deficient patients warrants further investigation. Dihydropyrimidine dehydrogenase deficiency, if undiagnosed, can lead to death. In addition to severe to life-threatening toxicities akin to 5-fluorouracil, capecitabine can lead to unusual variants of common toxicities, including HFS, in DPD-deficient patients.

Antimetabolites, Antineoplastic↗

Deaths in children during an outbreak of hand, foot and mouth disease in Peninsular Malaysia--clinical and pathological characteristics.

From July through December 1997, 11 previously healthy children in Peninsular Malaysia succumbed to an illness clinically characterised by an acute severe refractory left-ventricular failure, following a brief prodromal illness, in the midst of an outbreak of hand, foot and mouth disease (HFMD), similar to the reported experience in Sarawak and Taiwan. Retrospective reviews of the clinical features and results of laboratory, pathological and virological investigations of cases were conducted. The median age of the 11 case-patients was 31 months (range, 13 to 49 months); 6 were males. A brief prodromal illness of 3 days (range, 2 to 5 days) was characterised by fever (axillary temperature > 38 degrees C) (100%), oral ulcers (72%), extremity rashes (45%) and significant vomiting (55%). Upon hospitalisation, 7 of 11 case-patients had features suggestive of cardiogenic shock, while 4 of 11 case-patients developed shock during hospitalisation as evidenced by marked sustained tachycardia (heart rate > or = 180 beats per minute), poor peripheral pulses and peripheral perfusion, mottled extremities, pulmonary oedema (haemorrhagic pulmonary secretions in 8 of 11 cases during tracheal intubation, often precipitated by conservative crystalloid boluses, and radiographic evidence of acute pulmonary oedema in 5 of 7 cases) and markedly impaired left ventricular function on echocardiographic examination (7 of 7 cases). Three of 4 case-patients had aseptic meningitis while one case-patient also had an acute flaccid paraparesis. Despite supportive therapy, death occurred within a median of 13.4 hours following hospitalization. Post-mortem findings (all 8 specimens examined) consistently demonstrated brain-stem encephalitis with foci of neuronal necrosis and micro-abscesses. None of the 11 specimens examined revealed histological evidence of myocarditis. Enterovirus 71 (EV71) was detected in 10 of 11 case-patients, many (7) from various sterile tissue sites (5 from central nervous tissues). No other viruses were isolated or identified. Clinical features and pathological studies closely paralleled the reported experience in Sarawak and Taiwan. The uniform necropsy findings of necrotizing brain-stem encephalitis coupled with essentially normal myocardial histology, in concert with the concurrent and consistent detection of EV71 points to a primary EV71 encephalitis; as yet unclear neurogenic mechanisms may account for the cardiovascular manifestations.

Child, Preschool↗