CCS was first described by Cronkhite and Canada in 1955 [
9]. CCS can develop in all ethnic groups, but the most frequently affected populations were European or Asian descent and most of the cases were reported from Japan [
10]. The onset age was mainly between 50 and 70 years old [
2]. A slight male predominance was noted [
10], the ratio of male to female was about 1.3 ~ 2.3:1 [
2].
The etiology of CCS remains unclear. Patients with CCS accompanied by vitiligo, systemic lupus erythematosus, scleroderma, hypothyroidism and membranous glomerulonephritis have been reported in the literature [
8,
11‐
13], as well as CCS has been seen in association with antinuclear antibodies, which provide evidences to support CCS to be immune-mediated [
11]. Histologic findings of increased autoimmune-related IgG4 antibody in CCS polyps and treatment responses to immunosuppressants are also consistent with an autoimmune mechanism underlying CCS [
8]. Eric ward reported that mast cells were seen on histopathologic analysis of intestinal biopsies and a combination regimen containing H2-receptorantagonists, cromolyn sodium and loratadine was effective, which indicates the possible role of mast cell dysfunction in the pathogenesis of CCS [
3]. Goto et al reported that stresses, such as excessive physical exertion and mental strain, may trigger this syndrome. He also reported a frequency (3%) of concurrent psychiatric disorders in patients with CCS [
14]
. Mental stress may cause local inflammation in the gastrointestinal mucosa [
11]. CCS is characterized by gastrointestinal polyposis and ectodermal abnormalities. The polyps are characteristically distributed throughout the entire gastrointestinal tract except esophagus [
1]. The histopathologic types of the polyps have recently been reported as inflammatory, non-neoplastic, or retention polyps [
15]. However, gastrointestinal malignancies can be as high as 15% [
1]. The neoplasms develop primarily in the colon and less frequently in the stomach [
4]. Whether malignant lesions arise from preexisting polyps or coincidentally are a doubt. A study showed that serrated adenoma of the polypoid lesions was retrospectively found in 10 (40%) out of 25 CCS cases with colon cancer [
15]. Serrated adenoma have potential to be malignant and is often difficult to detect by endoscopy [
16]. Moreover, both serrated adenoma and hyperplastic polyps are of sessile type and possess saw-toothed, elongated, and dilated crypts. However the latter does not show significant nuclearatypia in histopathological examinations, so serrated adenoma may be considered to be hyperplastic polyps by mistake. It suggests that CCS associated with colorectal cancer may frequently have polyps containing serrated adenoma lesions [
15]. Ectodermal changes may be secondary to malabsorption [
11]. In the case we report, ectodermal changes occurred 2 months after the onset of gastrointestinal symptoms. With the improvement of diarrhea, hyperpigmentation relieved. However, there are a few reports in which ectodermal changes preceded the gastrointestinal manifestations.
Medical treatment regimens reported in the literature vary. Corticosteroid, anabolic steroids, various antibiotics, dietary supplementation, ranitidine, and symptomatic treatment have all been used. Patients commonly have only temporary symptomatic improvement [
3]. It is reported that steroid-resistant CCS was successfully treated by cyclosporine and azathioprine [
5], and a case was successfully treated by anti-tumor necrosis factor antibody after poor therapeutic effect of corticosteroids, antiplasmin agents, and azathioprine [
6]. A CCS patient associated with HP infection achieved remission after treatment with anti- Helicobacter pylori
regimen [
7]. SASP was effective in eradication of the inflammatory polyposis [
4]. Surgery may be indicated for the treatment of bowel complications, such as severe protein-losing enteropathy, persistent haematochezia, malignant transformation [
1,
8,
17] and rarely for removing the polyps burden [
8]. The progressive course of CCS makes the mortality up to 55% [
3], frequently due to complications such as anemia, gastrointestinal bleeding, congestive heart failure, and septicemia [
5]. Therefore, it is important to be diagnosed early to provide appropriate treatment and follow up. The treatment outcome in case report is encouraging, but it has been not confirmed by mass of evidence-based medicine.