Case report

Cronkhite–Canada syndrome: A case report and reviewof literature

Lin Yun XUE,*1 Ren Wei HU,* Shu Mei ZHENG,* De Jun CUI,* Wei Xia CHEN† & Qin OUYANG*

Departments of *Gastroenterology and †Radiology, West China Hospital, Sichuan University, Chengdu,Sichuan Province, China

INTRODUCTION

Cronkhite–Canada syndrome (CCS) is an uncommonnon-inherited disease with unknown etiology, whichis characterized by diffuse gastrointestinal polyps,dystrophic nail changes, alopecia, cutaneous hyper-pigmentation, diarrhea, abdominal pain, anorexia,hypogeusia, weight loss, hypoalbuminemia and elec-trolyte abnormality. Early manifestations of CCS arenonspecific; therefore, it is sometimes difficult to dif-ferentiate between CCS and intestinal tuberculosis(ITB) or inflammatory bowel disease including ulcer-ative colitis (UC) and Crohn’s disease. Here we reporta case of CCS that was initially misdiagnosed as UCand ITB.

CASE REPORT

A 61-year-old man was admitted to our hospital com-plaining of abdominal pain and mucous, bloody diar-rhea more than 10 times/day for 6 months, togetherwith alopecia, cutaneous hyperpigmentation, ony-chodystrophy, hypogeusia, palpitation, edema and aweight loss of more than 10 kg.

Two months before this admission, colonoscopyexamination from another hospital showed numerous

red edematous polyps with erosion and superficialulcers throughout the colon and rectum. Histologicalexamination revealed the infiltration of lymphocytesin the lamina propria with adenomatous polyps in therectum and colon. UC was suspected and the patientwas treated with mesalazine (3 g/day for 2 months)without any improvement.

Physical examination showed alopecia of thescalp and eyebrows and diffuse hyperpigmentationon his face, both palms and limbs, soles and back(Fig. 1a–d), dystrophic changes of all the nails(Fig. 1e,f) and edema in the lower extremities. Bio-chemical analysis showed increased levels of lactatedehydrogenase and hydroxybutyrate dehydrogenase of236 U/L and 196 U/L, respectively (normal range 110–220 U/L and 72–182 U/L), decreased hemoglobin(108 g/L), total protein (33.6 g/L) and albumin(16.1 g/L). Electrolyte analysis showed potassium2.41 mmol/L, calcium 1.60 mmol/L, magnesium0.48 mmol/L and inorganic phosphorus 0.73 mmol/L.The patient had positive serum anti-tuberculosis anti-body but negative tuberculin purified protein derivative(PPD) skin test. Immunity test showed immunoglobu-lin M (IgM) 332.0 mg/L (normal 700–2200 mg/L),complement component 3 (C3) 0.534 g/L (normal0.785–1.52 g/L) and complement component 4 (C4)0.135 g/L (normal 0.145–0.36 g/L), whereas anti-nuclear antibody was probable positive (�). Thepatient also suffered from paroxysmal atrial fibrillationand bradycardia.

A repeated colonoscopy (Fig. 2) showed numerous,irregularly sized, reddish and edematous sessilepolyps accompanied by diffuse erosions and superfi-cial ulcers throughout the colon and rectum, whichwere more severe in the ascending colon and ileocecalarea. Histological analysis revealed the combinative

Correspondence to: Qin OUYANG, Department of Gastroenterology,West China Hospital, Sichuan University, 37 Guoxue Alley, Chengdu610041, Sichuan Province, China. Email: qin.ouyang@163.com

1Current address: Department of Gastroenterology, The First Hospitalof Putian City, Fujian Medical University, Putian, Fujian Province,China.

© 2012 The AuthorsJournal of Digestive Diseases © 2012 Chinese Medical AssociationShanghai Branch, Chinese Society of Gastroenterology, RenjiHospital Affiliated to Shanghai Jiaotong University School ofMedicine and Wiley Publishing Asia Pty Ltd.

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Journal of Digestive Diseases 2013; 14; 203–206 doi: 10.1111/1751-2980.12016

203

changes of lymphocyte infiltration in the laminapropria, together with inflammatory and hyperplasticpolyps, adenomatous hyperplasia and canalicularadenoma. Computed tomography (CT) showedsmall nodules with a fiber shadow strip in the apex

and middle lobe of the right lung (Fig. 3), suggestingtuberculosis.

The patient was then diagnosed as ITB and was treatedwith isoniazid, rifapentine, ethambutol and pyrazina-mide. Two weeks later he suffered more severe bloodydiarrhea, but serum cortisol and thyroid hormonewere normal. A repeated sputum culture and acid-faststaining were negative for tuberculosis. The derma-tologist excluded fungal infection, which could causesimilar changes of the nails. Based on the ineffective-ness of anti-tuberculosis therapy and all the symptomsand signs observed, a diagnosis of CCS was estab-lished. Esophagogastroduodenoscopy was then per-formed, showing red, edematous and filiform polypswith giant folds mainly in the gastric antrum (Fig. 4a),without Helicobacter pylori (H. pylori) infection. Histo-logical analysis showed edema and infiltration of lym-phocytes in the lamina propria of the gastricspecimen. Barium enema examination of the smallintestine showed intestinal segmental dilatationmainly in the ileum, and rounded filling defects. Cor-ticosteroid therapy was then started with i.v. hydrocor-tisone at 200 mg/day for 10 days and changed to oralprednisone at 40 mg/day combined with levofloxacininfusion (0.5 g/day) for 10 days. All the symptomsimproved one month later and his serum albuminincreased steadily up to 29.1 g/L. The morbid changesof the lung disappeared according to a repeated CTwhen he discharged. Oral prednisone was maintainedfor 5 months with 5 mg tapering at 2-week intervals,after which the drug was withdrawn; the symptomsand signs of the patient were dramatically relieved,

(a)

(e)

(c) (d)

(f)

(b)

Figure 1. Cutaneous hyperpigmentation of (a) palms, (b)limbs, (c) soles and (d) back, and dystrophic changes of(e, f) all the nails.

Figure 2. Colonosopic appearance of the patient showsnumerous, irregularly sized, reddish and edematous sessilepolyps with diffuse erosion and superficial ulcers.

Figure 3. Computed tomography shows lesser nodule withfiber strip shadow in the right lung.

Journal of Digestive Diseases 2013; 14; 203–206204 LY Xue et al.

© 2012 The AuthorsJournal of Digestive Diseases © 2012 Chinese Medical Association Shanghai Branch, Chinese Society of Gastroenterology, Renji Hospital Affiliated to

Shanghai Jiaotong University School of Medicine and Wiley Publishing Asia Pty Ltd.

and endoscopic findings were significantly improved(Fig. 4b,c). The patient had no relapse within the1-year follow-up.

DISCUSSION

CCS is a rare acquired non-familial syndrome, theetiology of which is still unknown. Immune abnor-mality, infection, mental stress, concomitant neo-plasm and physical fatigue are regarded as the mostfrequent precipitating factors for CCS1–5 and in arecently published article it was found to be related toH. pylori infection.6 From its initial description in1955 to 2002, 387 cases have been reported, withJapanese patients contributing over 75%.2,7,8 In Chinathe number of cases reported is also increasing.9 Themean age of onset is usually in the fifth to sixthdecade, with a slight male predominance in a ratio of3:2.8,10

The diagnosis of CCS is based on clinical and endo-scopic findings, including characteristic gastrointesti-nal polyps as well as ectodermal changes of alopecia,dystrophic nail changes and hyperpigmentation of theskin. Histopathological examination of the intestinalmucosae reveals edema of the lamina propria, cysticdilation of glands and inflammatory cell infiltration;the polyps are most frequently described as theinflammatory, hamartomatous, adenomatous andhyperplastic type.1,9,11 However, ectodermal changesare not an exclusive property of the disease, as similarchanges can be seen in hypoparathyroidism andkwashiorkor. The cutaneous features of CCS have beenattributed to malnutrition; however, these findingssometimes precede the gastrointestinal symptoms. Inthis case, the patient also suffered from paroxysmalatrial fibrillation and bradycardia. There has beenanother reported case of CCS combined with atrialfibrillation,12 but whether atrial fibrillation is relatedto CCS needs further research.

The differential diagnosis focuses on Peutz–Jegherssyndrome (PJS), juvenile polyposis syndrome (JPS),Gardner syndrome, Turcot syndrome and Ménétrierdisease. It was suggested that CCS might be related toPJS and JPS.8

Therapies for CCS have focused on nutrition supportand steroid therapy, sulfasalazine and mesalazine havealso been reported to be effective.13–15 The prognosis ofCCS is very poor with a reported mortality of 55% inone study.2 The cancerization rate of the polyps hasreached 13%.7 Patients usually die due to gastrointes-tinal bleeding, malnutrition and infection.1

(a)

(b)

(c)

Figure 4. (a) Esophagogastroduodenoscopy shows red,edematous and filiform polyps with giant folds, mainly inthe gastric antrum. (b) Colonoscopic and (c) esophagogas-troduodenoscopic appearances after treatment.

Journal of Digestive Diseases 2013; 14; 203–206 A case of Cronkhite–Canada syndrome 205

© 2012 The AuthorsJournal of Digestive Diseases © 2012 Chinese Medical Association Shanghai Branch, Chinese Society of Gastroenterology, Renji Hospital Affiliated toShanghai Jiaotong University School of Medicine and Wiley Publishing Asia Pty Ltd.

There are two reported cases of CCS that were firsttreated as UC,16,17 just like our patient. UC is charac-terized by recurrent episodes of diarrhea, which isoften bloody, with abdominal pain, malaise andweight loss.18 In active UC, erosion and ulcer ofvarious sizes as well as petechial hemorrhages can befound by colonoscopy. Following healing of mucosalulcers, elevated sessile reddish nodules (pseudopol-yps) appear. The polyps are inflammatory or hyper-plastic and, although rarely, sometimes may present asadenomatous polyps.19 However, UC primarily affectsthe colon, especially the left colon, without ectoder-mal changes. Diarrhea usually occurs first in CCS, fol-lowed by ectodermal changes a few months later.9,11 Atthe beginning there might be just inflammatorychanges without polyps in the gastrointestinal tract.Therefore, at the early stage of CCS, it may be difficultto differentiate it from UC.

ITB is difficult to diagnose due to its lack of specificsymptoms and variable manifestations dependingupon the anatomical localization of the disease. Allregions from the esophagus to the rectum may beinvolved, but ileocecal TB is predominant. Endoscopycan reveal ulcers, stenosis and irregular polyps in ITB.Neither clinical presentations nor endoscopic findingsare specific. The criteria for diagnosing ITB are thehistological evidence of caseating granuloma withacid-fast bacilli stained by Ziehl–Neelsen and cultureand/or polymerase chain reaction positivity. Tubercu-losis of other organs would help with the diagnosis,and diagnostic anti-tuberculosis therapy used to behelpful. Sometimes tuberculosis may coexist withCCS.

In conclusion, we reported a case of CCS complicatedby paroxysmal atrial fibrillation and bradycardia,which was initially misdiagnosed as UC and ITB.Steroid therapy was effective as both gastrointestinalpolyps and ectodermal changes were relieved. CCS israre and with nonspecific early manifestations, andclinicians need to pay more attention to the disease.

ACKNOWLEDGMENT

We would like to thank Professor Bin HU for his excel-lent work on the endoscopy.

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Journal of Digestive Diseases 2013; 14; 203–206206 LY Xue et al.

© 2012 The AuthorsJournal of Digestive Diseases © 2012 Chinese Medical Association Shanghai Branch, Chinese Society of Gastroenterology, Renji Hospital Affiliated to

Shanghai Jiaotong University School of Medicine and Wiley Publishing Asia Pty Ltd.