various causes of intractable hiccups have been reported ; however , to the best of our knowledge , there are no previous reports of either intractable hiccups due to esophageal candidiasis in an immunocompetent adult or improvement following antifungal therapy .
an esophagogastroduodenos - copy revealed several white deposits throughout the esophagus and extensive white deposits in the midesophageal diverticulum .
a mucosal culture showed candidiasis , which was suspected to be the cause of the intractable hiccups .
therefore , we concluded that esophageal diverticular candidiasis was the cause of his intractable hiccups .
physicians should consider esophageal candidiasis as one of the differential diagnoses for intractable hiccups , even in immunocompetent adults .
hiccups result from brief and intense inspiratory bursts in the diaphragm and inspiratory intercostal muscles , with reciprocal inhibition of the expiratory intercostal muscles .
after diaphragmatic contraction , glottic closure occurs immediately , minimizing the ventilatory effect and generating the characteristic sound and sense of discomfort.1 hiccups are usually transient , but some patients occasionally experience intractable hiccups .
although the causes vary , there are only a few case reports of intractable hiccups associated with esophageal candidiasis , all of which occurred in patients with aids.2 here , we report an extremely rare case of intractable hiccups caused by esophageal candidiasis in an immunocompetent adult .
an 87-year - old man presented to our hospital with intractable hiccups . in the last 2 years , he had twice experienced hiccups that persisted for several days and improved with the following symptomatic treatment from his primary physician : esomeprazole , metoclopramide , dimethicone , and prokinetic chinese herbal medicine ( i.e. , rikkunshito and daikenchuto ) .
although this was his third episode of hiccups , he had not experienced them in the previous year .
the patient described repetitive waxing and waning hiccup cycles lasting 3 days , with 47 days of relief .
he took a chinese herbal medicine with antispasmodic qualities , shakuyakukanzoto , which he received from his primary physician , and the symptoms resolved at first .
however , 3 months later , the hiccups lasted for an entire day and did not improve with symptomatic treatment ; therefore , he was referred to our hospital .
he did not exhibit dysphagia , chest pain , chest discomfort , nausea , or headache .
the patient reported frequent use of esomeprazole for hiccups and chronic use of amlodipine and bisoprolol for hypertension .
his temperature , other vital signs , and the findings from a physical examination of the chest and abdomen were normal .
his laboratory parameters were normal , with no evidence of an immunocompromised status , such as diabetes mellitus or aids ( table 1 ) .
cranial magnetic resonance imaging revealed chronic lacunar infarcts ; cerebral tumor or ventricle enlargement was not observed .
chest computed tomography showed a midesophageal diverticulum projecting rightward at the tracheal bifurcation ( figure 1 ) .
the midesophageal diverticulum was localized on the right wall approximately 30 cm distal to the incisors ( figure 2 ) .
white residue was observed at the diverticulum margin and was flushed out easily . in the diverticulum , extensive white deposits were observed .
the deposits in the diverticulum were biopsied . his - topathological examination ( hematoxylin and eosin staining ) showed significant inflammatory cell infiltration and acantholytic finely fragmented squamous epithelial cells ( figure 3a ) , grocott staining showed yeast and fungal filaments ( figure 3b ) , and mucosal culture revealed candida albicans .
the patient was prescribed 200 mg fluconazole once daily for 14 days , and the hiccups decreased markedly in frequency .
after 2 weeks of treatment , the residue and white deposits were absent from the entire esophagus and diverticulum in the egd views .
written informed consent was obtained from the patient for publication of this case report and any accompanying images .
the local ethics committee of hyogo prefectural kaibara hospital judged that the ethical review of this case was unnecessary .
virtually everyone experiences self - limiting , transient hiccups that last for several minutes or more .
last longer than 1 month.3 in our case , the patient had been experiencing intractable hiccups for 3 months .
however , the intractable hiccups stopped after the esophageal candidiasis had been treated successfully with oral fluconazole , which is an antifungal agent that is recommended as a first - line treatment for candidiasis by the japanese society for medical mycology and the european society of clinical microbiology and infectious diseases.4,5 therefore , we concluded that his intractable hic - cups were caused by esophageal candidiasis .
although the mechanism underlying hiccups is unclear , it is thought that stimulation of the afferent portion of the hiccup reflex arc comprising the phrenic nerve , vagus nerve , and sympathetic chain is transmitted through central nervous system connections , such as the phrenic nerve nuclei , medullary reticular formation , and hypothalamus , and finally reaches the efferent component that is composed of the anterior scalene muscles , external intercostal muscles , glottis , and diaphragm.3 transient hiccups are caused by gastric distension , sudden temperature change , alcohol ingestion , excessive smoking , and psychogenic factors.6 the causes of persistent or intractable hiccups vary appreciably and include irritation of the vagus nerve ( e.g. , pharyngitis , pneumonia , aortic aneurysm , and pancreatitis ) , central nervous system abnormalities ( e.g. , intracranial neoplasms , hydrocephalus , and meningitis ) , toxic - metabolic disease ( e.g. , uremia , diabetes mellitus , and electrolyte imbalance ) , diaphragmatic irritation ( e.g. , myocardial infarction , hepatosplenomegaly , and subphrenic abscess ) , drug intake ( e.g. , alpha methyldopa , short - acting barbiturates , and dexamethasone ) , infections ( e.g. typhoid fever , influenza , and tuberculosis ) , general anesthesia , postoperative complications , and psychogenic or idiopathic variables.6 esophagitis can cause persistent or intractable hiccups because of irritation of the thoracic branches of the vagus nerve ; however , to the best of our knowledge , there are only a few other case reports of intractable hiccups associated with esophageal candidiasis.2 furthermore , the present report appears to be the first to describe a case of intractable hiccups caused by esophageal candidiasis in an immunocompetent adult . in our case
, we suspect that inflammation of the esophagus stimulated the afferent portion of the hiccup reflex arc .
the presence of inflammatory cell infiltration in the biopsied specimen suggests that inflammation of the esophagus might have contributed to the hiccups .
the symptoms of esophageal candidiasis are dysphagia , odynophagia , nausea , vomiting , retrosternal pain , and gastrointestinal bleeding , although some patients are asymptomatic.79 because hiccups are atypical symptoms in esophageal candidiasis , they might be related to the esophageal diverticulum and the white residue , which was observed at the diverticulum margin .
however , it is difficult to imagine that the esophageal diverticulum caused the intractable hiccups by itself because the diverticulum remained , even after the hiccups improved .
furthermore , because the white residue was flushed out easily , it is unlikely that it had irritated the vagus nerve and caused intractable hiccups of several months duration .
esophageal candidiasis usually occurs in immunocompromised hosts , although sometimes it is present in immunocompetent adults .
other risk factors for esophageal candidiasis are acid - suppression therapy ( e.g. , proton pump inhibitors or histamine-2 receptor blockers ) , elderly age , use of antibiotics , malignancy , diabetes mellitus , chronic renal failure , use of corticosteroids ( systemic or inhalant ) , and use of another immunosuppressive agent.911 our patient had some of these risk factors ( i.e. , elderly age and use of proton pump inhibitors ) .
furthermore , he had esophageal diverticulum . although , we do not think that esophageal diverticulum itself caused the intractable hiccups , it may have become a hotbed of candidiasis . perhaps consequently , he had esophageal candidiasis in spite of his immunocompetent status .
clinicians should consider esophageal candidiasis as one of the differential diagnoses when treating a patient with intractable hiccups , especially if that patient is an elderly adult who is using acid - suppressing therapy or has existing esophageal diverticulum .
 introductionvarious causes of intractable hiccups have been reported ; however , to the best of our knowledge , there are no previous reports of either intractable hiccups due to esophageal candidiasis in an immunocompetent adult or improvement following antifungal therapy.case presentationan 87-year - old man presented with intractable hiccups . although the patient was immunocompetent , he used proton pump inhibitors . 
 an esophagogastroduodenos - copy revealed several white deposits throughout the esophagus and extensive white deposits in the midesophageal diverticulum . 
 a mucosal culture showed candidiasis , which was suspected to be the cause of the intractable hiccups . 
 after oral fluconazole had been prescribed , the candidiasis resolved and the hiccups improved . therefore , we concluded that esophageal diverticular candidiasis was the cause of his intractable hiccups.conclusionphysicians should consider esophageal candidiasis as one of the differential diagnoses for intractable hiccups , even in immunocompetent adults . 
Introduction
Case presentation
Conclusion
Introduction
Case presentation
Discussion
Conclusion