Discussion:
The increasing armamentarium of pharmacological agents has resulted in a multifactorial fusillade of effects within the gastrointestinal and cutaneous systems. The small intestine is the most common site of adverse drug reaction due to the delicate balance between the enteric and central nervous system1. Often there is a temporal relationship between the drug ingestion and onset of symptoms, but this can sometimes manifest inconsistently and unpredictably1,2. Very few cases of ARB induced sprue-like enteropathy, other than olmesartan, have been reported. There has only been one reported case with cutaneous manifestations and ARB induced sprue-like enteropathy. There have been several case reports and cohort studies over the last decade which have demonstrated a sprue-like enteropathy presenting with abdominal pain, chronic diarrhea, and weight loss in association with ARB use1,2. In 2016, Hammoudi et al published the first case of olmesartan induced enteropathy with ‘papulo-erythematous lesions and scabs’ with full resolution within a week following cessation of the medication3. The pathophysiology of ARB induced sprue-like enteropathy is currently unknown with even less understood regarding the connection to a cutaneous manifestation. However, the punch biopsy and duodenal samples did demonstrate findings consistent with drug eruption, and after months of symptoms, a few hospitalizations, and several failed therapies, the treatment that ended up improving her condition was discontinuation of the losartan.
Several studies have demonstrated that many of the common pathogenic pathways seen in celiac disease are also present within that of ARB induced sprue-like enteropathy. There is an increased number of CD8+ positive T cells, and granzyme positive B cells resulting in destruction of the lamina propria and epithelial layer2,5,6. Previous studies have demonstrated an increased number of CD8+ positive T cells which express interleukin 15 and 15R resulting in the disruption of tight junction complexes such as in refractory celiac sprue1. Given some of the known histopathology overlap observed in celiac disease and ARB induced sprue-like enteropathy, a cutaneous manifestation is not unexpected, although the cutaneous manifestations may differ. Celiac disease is associated with dermatitis herpetiformis whereas ARB induced sprue enteropathy may cause ulcerative lesions5,6. Our case of losartan induced enteropathy further suggests that sprue-like enteropathy with cutaneous manifestations may be a unique but rare class effect of ARBs and should be considered when evaluating patients with similar clinical findings.