Cronkhite-canada Syndrome (ccs) - a Rare Case Report

Introduction

Cronkhite-Canada syndrome (CCS) is a sporadic condition which involves tissues arising from the ectodermal germ cell layer. It is characterized by gastrointestinal hamartomatous polyposis, diarrhea, hypoproteinemia and cutaneous manifestations including alopecia, onychodystrophy, hyperpigmentation. Other symptoms such as dysguisea, hypoguisea and xerostomia due to zinc and cobalt deficiency have been reported in some patients. Its incidence is low but mortality is high. Only 500 cases of CCS have been reported around the world, with having approximately 60% overall mortality rate. The main age of presentation is 59 with a slight male predominance in the ratio 3 : 2, however, the majority of cases identified in age older than 50.

The very first case of Cronkhite-Canada syndrome was reported in 1955 by the internist Leonard Wolsey Cronkhite and the radiologist Wilma Jeanne Canada in the New England Journal of Medicine , yet the etiopathogenesis of this disease is not fully understanded, but there are two schools of thought exists: one that supports immunological mechanism , which is more believed and the other that supports infectious mechanism.

The latter was also considered because of histopathological findings of biopsy from gastrointestinal polyps showed inflammatory cells infiltration with mononuclear cells and eosinophils. While the CCS polyps infiltrated with IgG4 plasma cells; elevated antinuclear antibody; decreased manifestation of disease when treated with corticosteroids, and association with other autoimmune disease such hypothyroidism, systemic lupus erythematosus, rheumatoid arthritis and scleroderma strongly supports autoimmune pathophysiology of this disease. The only postulated risk factors for CCS include mental and physical stress.

Case Report

A 44-year-old Indian male residing in Canada for the past 16 years with a history of gout since 7 years presented with complaints of chronic diarrhea, intermittent bloody stools, nausea, abdominal pain, weight loss for 2 months, he would occasionally take alcohol for the past 10 years. He was on proton pump inhibitors for chronic gastritis, Allopurinol for gout, ibuprofen for symptomatic relief of gouty pain and after a week of Ibuprofen he spontaneously developed diarrhea which did not resolve with medication with increasing frequency up to 10 times a day, with his hair greying initially from his pubic advancing to his axillary hair, progressing towards mustache and beard with the scalp being the last affected site. He initially had intermittent abdominal cramps which turned into several bouts of abdominal pain. He began to shed all his hairs including nasal hairs causing continuous nasal discharge and dried nasal mucosa. and developed brittle nails which also started to fall off. During this period he suffered from severe malnutrition and lost almost 4 kg weight in 3 weeks.

On his first hospital, a git pathology was assumed, hence pantoprazole and antibiotics were prescribed after X-ray and blood works. On further investigation, he underwent an Esophagogastroduodenoscopy with biopsy which revealed small sessile polyps in the entire digestive tract except in the esophagus, he was soon started on corticosteroids, with a possible immune response leading to the formation of polyps, kept in mind. In the coming 5 weeks, he further lost 6 kg of weight with a loss of taste sensation. He then underwent video colonoscopy during which biopsy from colonic and gastric polyps was taken for immunohistological findings.

On physical examination, he was fairly built, poorly nourished, weighing 68 kg, presenting without eyebrows, baldness, onychodystrophy with loss of finger and toenail. The gouty swelling was present on the right toe. There were hyperpigmented oval spots measuring 5mm to 15mm in diameter all over his palms and sole. His palms were sweaty with some scattered hyperpigmentation noted on different parts of the body. Physical exam also showed bilateral symmetric edema in lower extremities. No other significant findings were present.

Symptomatic treatment initially included corticosteroids, analgesics, broad-spectrum antibiotics. Nutritional support was provided with multivitamin tablets, calcium and iron. PPIs were stopped. Protein rich diet was recommended. It reduced symptoms but not effectively. Then in India, he stopped all medications and started ayurvedic powder with a diet based treatment. Ayurvedic powder was mixture of dried fruit of Aegle marmelos (Indian bael), Zingiber officinale (Dried ginger), Gymnema sylvestre leaf extract in ratio of 1:1:2 respectively. Daily Diet consisted of turmeric milk, cracked wheat and puffed rice only. Calcium and Iron folic acid tablets were supplemented. This diet was followed for six week. By the end of sixth week there was only 2 episodes of bloody diarrhea, stool frequency decreased to 5-6 times from 10 times per day.

After six week, khichri, an Indian dish made from cracked wheat and lentils was added into his diet. Ayurvedic powder was replaced by ayurvedic tablets consisting of bark extracts from Holarrhena antidysenterica, root extracts from Plumbago zeylanica, root extracts of Piper longum, leaf extracts of Bryophyllum pinnatum and bark extracts of Cinnamomum camphora. Six weeks later he started growing white hair on his eyebrow, mustache and pubic area. Frequency of stool decreased to 3-4 times a day. Hair started blackening, weight increased by 2 kg and lastly new nails started growing. Also CT scan at the end of the 12 weeks from starting diet based treatment evaluatory CT Scan was performed which supported the improvement in pathology. Currently he is off all ayurvedic medication and taking Mesalazine 1200 mg, four times a day.

Laboratory

His eosinophil count was 7.4% (normal range: 0.0 – 6) with an absolute count of 0.58 x 10^3 / μl (normal range : 0-0.5), his haemoglobin was 12.5 g/dl (normal range 13 – 17), he had a Mean Corpuscular Haemoglobin of 26 pq (normal range 27-32), Mean Corpuscular Haemoconcentration of 26.5 g/dl (normal range 31.5 – 34.5 ) Red Cell distribution Width – Sd of 53.6 fL (normal range 39-46) Red Cell distribution Width – CV of 14.6 % (normal range of 11.6-14) , total 25-OH vitamin D of 6.5 ng/ml, Calcium levels of 8.09 mg/dl (normal 8.8 – 10.6 , uric acids levels of 9.4 (normal range 3.7 – 9.2), Estimate Glomerular filtration rate of 81 (between 60 – 89 indicates a mild decrease

Endoscopy

Esophagogastroduodenoscopy revealed polyps with stomach villous atrophy and a normal esophagus. A few hemorrhagic foci were present on in the inner surface of the stomach. In the duodenum, rugal folds were thickened and had brownish discoloration. Multiple polyps were seen in the body and antrum of the stomach; the first, second and third parts of the duodenum. Colonoscopy revealed multiple polyps and inflammation throughout the colon.

The intensity of inflammation and density of polyps were more in the ascending colon, transverse colon with a reduced number seen in sigmoid colon and rectum while terminal ileum noted normal. Piles were present. On the basis of this abnormal features, the duodenum, entire stomach, and polyps were extensively biopsied for histopathological imaging. Histopathology Duodenal biopsy revealed subtotal to total villous atrophy, moderately expanded oedematous lamina propria, mononuclear inflammatory infiltrate with prominent eosinophils, scattered foci of crypt and glandular dilation , mildly increased intraepithelial lymphocytes not reaching diagnostic threshold for marsh lesion without any dysplasia or malignancy while Antral and Oxyntic gastric mucosa exhibited prominent expansion of lamina propria by edema, mononuclear inflammatory infiltrate with prominent eosinophils, architecture abnormalities including foveolar hyperplasia and dilatation with focal intestinal metaplasia. Foci of epithelial attenuation, denuded surface gastric epithelium without surface erosion were present. Scattered hemosiderin-laden macrophages indicated prior hemorrhage.

The biopsy of polyps showed benign polypoid colonic tissue with a few dilated, abscessed crypts and benign polypoid gastric mucosa having chronic inflammation with intestinal metaplasia without dysplasia. Immunostaining CD34, CD117 and CD68, highlighted prominent vascularity especially on the surfaces, patchy prominent number of mast cells, and large number of macrophages, respectively. Actin and Desmin immunostains demonstrate splaying of smooth muscle fibres in between glands and foveolar pits. Immunostaining with CAM5.2, CK AE1/AE3, and EMA gained negative result for any infiltrating malignant epithelial cell. Also, screening with IgG4 yielded negative result. Computed Tomography 10 weeks post treatment CT showed mild bilateral pelviectasis indicating a distended urinary bladder otherwise showed no other abnormalities.

Discussion

The overall findings suggested Cronkhite-canada syndrome ,which is a rare protein-losing gastroenterocolopathy typically characterized by diffuse gastrointestinal polyposis as well as ectodermal changes such as hair loss of the scalp and body, nail dystrophy (thinning, splitting, separation from the nail bed and shedding), and skin hyperpigmentation, usually of the extremities (in particular the hands), face (including labial and buccal mucosa ) and neck, of interest, the provided clinical notes indicate that the patient has had some weight loss as well as alopecia areata progressing to the universalis variant. While the most common endoscopic appearance in the upper gastrointestinal tract is that of diffuse polyposis, mostly sessile, a second less common scenario is diffusely thickened or atrophic rather than polypoid mucosa , often raising the differential diagnosis an infiltrative neoplastic process ( especially lymphoma or linitis plastica with carcinomatosis).

Differential diagnosis includes rare hamartomatous GI polyposis (e.g. juvenile polyposis, peutz- jeghers syndrome, menetrier, multiple hyperplastic polyposis and eosinophilic gastroduodenitis. The hermartamous GI polyposis are considered unlikely in view of the lack of the polyps in stomach on endoscopy, the diffuse nature of the disease, and the presence of marked villous atrophy in the duodenum.

Menetrier disease is also unlikely as it typically spared the antrum and does not involve the antrum, but they are seldom so numerous as to diffusely involve the entire stomach. Eosinophilic gastroduodenitis is considered due to the prominent number of eosinophils; however , it does not usually exhibit this degree of lamina propria edema as well as the described architectural abnormalities, no peripheral eosinophilia is noted in the patients bloodwork.