Appeal type: Experimental/Investigational
Decision: Overturned

Diagnosis: Microscopic Colitis
Treatment: Fecal Calprotectin 
The insurer denied the Fecal Calprotectin 
The denial is overturned.

The patient is a female with auto-immune hepatitis managed with ursodiol, celiac disease managed with strict gluten avoidance, and lymphocytic colitis managed for several years with budesonide 9mg (milligrams) daily. Her additional PMH (past medical history) includes osteopenia, left shoulder surgery, L5-S1 (fifth lumbar spine vertebra - first sacral vertebra) fusion, hysterectomy, Caesarian-section.

Per the last office visit the patient averages two to three stools daily, without blood, but occasionally diarrheal. Dietary noncompliance results in LLQ (left lower quadrant) abdominal pain. Abdominal exam was normal as documented.

In routine evaluation of the patient's occasional diarrhea, her provider ordered stool studies including a pathogen panel and fecal calprotectin analysis. After sample collection, calprotectin results were reported as normal =42 ug/g (micrograms per gram) (range 0-120).  At issue is the calprotectin assay.

Yes, the health plan should cover the Fecal Calprotectin.
Calprotectin (FC), when measured in feces, is generally not investigational/experimental. It is commonly and increasingly used in clinical practice to differentiate between non-organic and inflammatory intestinal disorders, especially to identify inflammatory bowel disease (IBD) and to monitor patients with IBD (inflammatory bowel disease) under treatment and to predict the risk of recurrence of active disease prior to clinical relapse. (1)

In Mosli's comparative meta-analysis of 19 studies, the diagnostic accuracy of C-reactive protein (CRP), fecal calprotectin (FC), or stool lactoferrin (SL) was examined against endoscopy as a gold standard in patients with symptoms/signs consistent with active IBD (inflammatory bowel disease). The pooled sensitivity and specificity estimates for CRP (C-reactive protein), FC (fecal calprotectin), and SL (stool lactoferrin) were 0.49 (95% confidence interval [CI] 0.34-0.64) and 0.92 (95% CI [confidence interval] 0.72-0.96), 0.88 (95% CI [confidence interval] 0.84-0.90) and 0.73 (95% CI [confidence interval] 0.66-0.79), and 0.82 (95% CI [confidence interval] 0.73-0.88) and 0.79 (95% CI [confidence interval] 0.62-0.89), respectively. FC (fecal calprotectin) was found to be more sensitive than CRP (C-reactive protein) for Appellant's indication. (2)  Similar results were reported by Menees' meta-analysis of 140 relevant citations that cross-referenced CRP (C-reactive protein), FC (fecal calprotectin), SL (stool lactoferrin), and erythrocyte sedimentation rate (ESR). (3)

Relative to the patient's specific case, Bjarnason opines: "the fecal calprotectin test is a functional quantitative measure of intestinal inflammation, and it is inflammation- and not disease-specific. It is a test that usually supplements endoscopy clinically and, at times, can even replace the procedure. Fecal calprotectin certainly has the potential to serve as a diagnostic screening test (as opposed to merely a diagnostic test)."

Specific to the patient's indication, Von Arnim et al (6) showed that fecal calprotectin levels (FC) were significantly higher in patients with active microscopic colitis including lymphocytic colitis (MC) (median 48 ug/g [micrograms per gram] [23106]) compared to patients with IBS (irritable bowel syndrome) (median 2 ug/g [micrograms per gram] [1111.83]), P=0.0001 using an ELISA (enzyme-linked immunosorbent assay). FC (fecal calprotectin) level of patients with MC (microscopic colitis) in remission was 22 ug/g (micrograms per gram) (1106.4), which is similar to those identified in patients with IBS [irritable bowel syndrome]."

Others have echoed the sentiment that fecal calprotectin can serve, other than for inflammatory colitis, as a biomarker of disease activity in such conditions as microscopic colitis, acute gastroenteritis, Clostridium difficile infection, colorectal cancer, diverticular disease, celiac disease. (7,8)

Yes, the Fecal Calprotectin is likely to be more beneficial.
Standard testing requires colonoscopic biopsy with its attendant risks. Fecal calprotectin is readily available, and as demonstrated by the citations above, is a reliable noninvasive biomarker of the patient's microscopic (lymphocytic) colitis.