ADIS Assignment #1

Jimmy Nguyen
Roseman University
South Jordan Campus
Pharm D | Class of 2017

A patient who has Crohns disease status post colectomy with chronic colostomy, stage IV CKD,
CAD, & type 2 diabetes mellitus comes into the ER with complaints of recent bilateral foot pain.
The patients ESR was elevated but the physician has ruled out gout and cellulitis. The physician
is concerned about a possible drug-induced arthritis with the patients current medications.
The patients home medications include aspirin, gabapentin and Tradjenta. The aspirin is to help
with his CAD and the gabapentin is most likely being used to help with diabetic neuropathy.
These two medications are not the probable cause of the patients drug-induced joint pain. The
patient was recently started on Tradjenta 5 mg daily to help with glucose control. Tradjenta can
potentially cause an increase in ESR levels which explains the patients elevated ESR levels. 1
Tradjenta can also raise the levels of uric acid within the body which could potentially cause
gout, although the diagnosis has been ruled out. There is a potential that drug-induced arthritis
can develop upon starting Tradjenta.
After a few weeks of being placed on the medication, the patient began experiencing a fairly
acute onset of pain in the plantar aspects of his feet bilaterally. There have been reported cases
of DPP4 inhibitors, like Tradjenta, causing drug-induced arthritis a few weeks after initial
treatment of the medication.2 The reported cases state that patients began taking a DPP4 inhibitor
and developed drug-induced arthritis within a short period of initial treatment. Some of the
reported cases were diagnosed as remitting seronegative symmetrical synovitis with pitting
edema (RS3PE) which is distinguished by possible tenderness, swelling or limited motion of the
joints.3 The theory of the induced pain in the joints may be from the inhibition of serine protease
DPP4 which is constitutively expressed in many cell types including cells that mediate

ADIS Assignment #1
Jimmy Nguyen
Roseman University
South Jordan Campus
Pharm D | Class of 2017

inflammatory responses. These may include T-lymphocytes, fibroblasts and macrophages. The
inhibition of serine protease DPP4 may disturb inflammatory balances and could cause problems
in the bone and joints.4
The symptoms of acute pain in the patients feet will likely be resolved upon discontinuation of
the medication within a few days up to a month. 5 Patients who develop medication induced
arthritis may experience a relapse in symptoms if switched to another DPP4 inhibitor suggesting
that the medication class is the reason to the pain development. 2 Tradjenta would have been the
only DPP4 inhibitor acceptable in patients with stage IV CKD because there is not a need to be
dose adjusted in kidney disease.6 This patient should not be switched to any other DPP4
inhibitors due to his stage IV CKD and the potential risk of redeveloping the foot pain.
Based upon the literature and case studies, the patient will benefit from being switched off of the
Tradjenta to another glucose maintenance medication that is not in the DPP4 inhibitor class. The
DPP4 inhibitors have shown evidence to cause medication-induced arthritis which can be
resolved within a few weeks upon discontinuation. If the patient is taken off of the medication,
the symptoms will resolve.

ADIS Assignment #1
Jimmy Nguyen
Roseman University
South Jordan Campus
Pharm D | Class of 2017

Works Cited
1. Salam A, Henry R, Sheeran T. Acute onset polyarthritis in older people: Is it RS3PE
syndrome?. Cases J. 2008;1(1):132. doi:10.1186/1757-1626-1-132
2. Crickx E, Marroun I, Veyrie C, et al. DPP4 inhibitor-induced polyarthritis: a report of
three cases. Rheumatol Int. 2014;34(2):291-292. doi: 10.1007/s00296-013-2710-7.
3. Yamauchi K, Sato Y, Yamashita K, et al. RS3PE in association with dipeptidyl peptidase4 inhibitor: report of two cases. Diabetes Care. 2012;35(2):e7. doi: 10.2337/dc11-1995
4. Ospelt C, Mertens JC, Jngel A, et al. Inhibition of fibroblast activation protein and
dipeptidylpeptidase 4 increases cartilage invasion by rheumatoid arthritis synovial
fibroblasts. Arthritis Rheum. 2010;62(5):1224-1235. doi: 10.1002/art.27395.
5. Yokota K, Igaki N. Sitagliptin (DPP-4 Inhibitor)-induced Rheumatoid Arthritis in Type 2
Diabetes Mellitus: A Case Report. Intern Med 51. 2012;2041-2044. doi:
10.2169/internalmedicine.51.7592
6. Richard KR, Shelburne JS, Kirk JK. Tolerability of dipeptidyl peptidase-4 inhibitors: a
review. Clin Ther. 2011;33(11):1609-1629. doi:10.1016/j.clinthera.2011.09.028