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.