Blame the drug: a rare case of doxycycline-induced recurrent pancreatitis

Doxycycline is a broad-spectrum bactericidal antibiotic belonging to the tetracycline class. It’s a comparatively secure drug with reported unwanted side effects equivalent to gastrointestinal signs, discoloration of bones and tooth, sensitivity to mild, and renal toxicity. Acute pancreatitis (AP) is an unusual opposed impact with just a few circumstances reported within the literature. Though tetracycline has been described as a attainable causative agent of drug-induced pancreatitis (DIP), doxycycline has hardly ever been implicated. Right here we current a case of a 65-year-old feminine affected person who developed doxycycline-induced pancreatitis after inadvertently beginning a drug for community-acquired pneumonia. The commonest causes of pancreatitis have been excluded throughout her hospitalization and she or he was subsequently identified as DIP. It was efficiently handled with discontinuation of the offending agent and supportive remedy. It’s essential for clinicians to pay attention to the attainable affiliation between doxycycline and pancreatitis to additional support analysis and immediate remedy of this situation.

an introduction

Acute pancreatitis (AP) is a extreme illness that impacts roughly 45 out of each 100,000 individuals yearly [1]. Gallstones and alcohol are the 2 most typical causes, accounting for 70%-80% of all circumstances [2]. Different much less widespread etiologies embody autoimmune illness, hyperlipidemia, hypercalcemia, endoscopic cholangiopancreatography (ERCP), an infection, trauma, inflammatory bowel illness, ischemia, and tumors. [1-2]. A particularly uncommon reason behind pancreatitis is drug-induced pancreatitis (DIP) with an estimated incidence of solely 0.1%-2% [1-2]. The World Well being Group has reported 525 medicine related to AP and a direct causal relationship in 31 medicine. Though tetracycline has been described as a attainable causative agent of DIP, doxycycline has hardly ever been implicated. [1]. Doxycycline is a drug generally prescribed for a variety of bacterial infections together with tender tissue infections, respiratory infections, sexually transmitted ailments, and Lyme illness. [2]. AP is an unusual opposed impact with just a few circumstances reported within the literature. Given how generally doxycycline is prescribed clinically, it’s important that clinicians are conscious of the intense opposed results related to using doxycycline together with DIP. We hope to construct on current information and strengthen the affiliation between doxycycline use and pancreatitis by offering a uncommon case report of a affected person who developed recurrent pancreatitis after taking doxycycline.

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A 65-year-old girl with a earlier medical historical past of DIP, rheumatoid arthritis (RA) and community-acquired pneumonia (CAP) introduced to the emergency division with a significant criticism of nausea, fatigue, and epigastric ache radiating to her once more inside the previous two days. The ache was rated 8/10 in severity, worse with consuming, and occurred constantly all through the day with none mitigating components. The affected person denied any current modifications aside from the truth that she had began taking doxycycline three days earlier for her remedy. The affected person additionally denied any historical past of smoking, alcohol, insect bites, stings, trauma, or current endoscopic procedures.

Upon arrival, she had a fever of 100.4 levels Fahrenheit and a tachycardia. Bodily examination was important for epigastric tenderness with no proof of stomach guarding or rigidity. Main labs have been notable for leukocytosis 33.9 × 103 μl and lipase 3,431 IU/l with unobserved ranges of serum calcium, lactate, liver enzymes, and lipid plaque as summarized within the desk. 1. Stomach and pelvic computed tomography revealed peripancreatic fluid and fats according to AP (Fig 1). Then an ultrasound was carried out in the suitable higher quadrant and no gallstones or bile duct distention have been seen (Fig. 2). The lipid panel was additionally requested to research the etiology of pancreatitis, nevertheless, it returned inside regular limits. Due to her historical past with RA, her IgG4 stage was requested to exclude sort I autoimmune pancreatitis, which was additionally unremarkable. Blood cultures have been additionally withdrawn throughout admission on account of fever and leukocytosis. Nonetheless, no bacterial development has been reported. Then I began robust intravenous hydration, antiemetics, and ache management. After excluding the commonest etiology of pancreatitis, doxycycline-induced pancreatitis was identified and doxycycline was discontinued. Her lipase improved to 573 IU/L on the second day, and 530 IU/L on the third day as proven within the desk 1. She reported symptom reduction with discontinuation of medicine and supportive care. Upon additional questioning, she said that her final bout of pancreatitis additionally occurred within the setting of utilizing doxycycline to deal with cellulitis two years in the past. She has shunned utilizing doxycycline since that episode, nevertheless, was inadvertently prescribed it and ended up with recurring signs. The affected person was then discharged residence in an improved and secure situation and instructed to keep away from future use of doxycycline.

Labs day 1 the second day day 3 reference group
White cell depend (103 µL) 33.9 23.9 10.3 4.0-10.5
Hemoglobin (g/dL) 12.2 13.3 11.3 13.7-17.5
Hematocrit (%) 40.9 37.4 40.2 40.1-51
platelets (103 µL) 254 199 306 150-400
MCV (fL) 98.1 97.4 95 79.0-92.2
Sodium (mmol/L) 140 138 138 136-145
Potassium (mmol/L) 3.7 3.5 4.4 3.5-5.1
Chloride (mmol/L) 109 110 105 98-107
Carbon dioxide (mEq/L) 27 23 27 21-32
Glucose (mg/dL) 74 68 124 74-106
BUN (mg/dL) fifteenth 9 18 7-18
Creatinine (mg/dL) 0.64 0.43 0.58 0.6-1.30
GFR (ml/min) 112 178 121 0-120
Calcium (mg/dL) 8.7 8.2 8.5 8.5-10.1
Lipase (unit/liter) 3283 573 530 73-393
Complete Bilirubin (mg/dL) 0.4 0.2 0.3 0.2-1.0
AST (unit/liter) fifteenth 12 7 15-37
ALT (items/liter) 12 19 fifteenth 13-56
Alkaline phosphatase (unit/liter) 63 73 57 46-116
Magnesium (mg/dL) 2.1 2.4 2.1 1.8-2.4
Lactic acid (mmol/L) 0.7 0.4-2.0
Triglycerides (mg/dL) 69 0-149
Complete ldl cholesterol (mg/dL) 138 <200
Computed tomography of the abdomen and pelvis without contrast reveals evidence of pancreatic edema with braiding of fluid around the pancreas and fat.  -

Ultrasound - right upper quadrant - reveals - shows - unnoticeable - gallbladder - without evidence - gallstones - or wall thickening.  -

Talk about

Drug-induced pancreatitis is a uncommon phenomenon with an estimated whole incidence of lower than 2% of all AP . circumstances [1]. Up to now, 31 totally different medicine have been recognized as particular causes of DIP with the commonest being mesalazine, azathioprine, and simvastatin. [2]. Most of our understanding of this illness course of is predicated on case reviews that set up a causal relationship between pancreatitis and a attainable offending agent within the absence of different widespread etiologies. The dearth of scientific options of DIP makes it troublesome to diagnose and additional complicates it. Tetracyclines have been implicated as a selected trigger [3] of pancreatitis and is classed beneath class 1 B of the Badaloff classification of DIP [4]. Nonetheless, doxycycline stays an unusual reason behind DIP. To our information, solely six circumstances of doxycycline-induced pancreatitis have been reported within the literature with it being one of many first reported circumstances of recurrent pancreatitis. [5].

The commonest causes of AP are alcohol use and gallstones make up 70%-80% of all circumstances adopted by hypertriglyceridemia and procedures equivalent to endoscopic cholangiopancreatography (ERCP) [6]. Different, much less widespread causes are often patient-specific and embody autoimmune causes, infections, and trauma. As seen within the case presentation above, the commonest etiology of pancreatitis was initially excluded as she had no historical past of serious alcohol abuse or current endoscopic procedures equivalent to ERCP. Proper higher quadrant ultrasound was damaging for gallstones and serological assessments confirmed regular lipid ranges. Moreover, she denied any ticks, insect bites, journey or trauma. Autoimmune pancreatitis was additionally thought of as a possible differential given her historical past with RA, nevertheless, she examined damaging for IgG4 antibodies. Thus, we have been capable of remove the above as causes for its AP. Nonetheless, her current use of doxycycline to deal with her vascular scars simply three days earlier than her signs started raised DIP’s suspicion.

Our affected person developed pancreatitis inside three days of publicity to doxycycline and his signs resolved instantly upon discontinuation of the drug. DIP is identified after the widespread etiology of pancreatitis has been excluded, adopted by scientific enchancment after discontinuation of the offending agent as described within the above case. Nonetheless, along with discontinuing doxycycline, she was additionally concurrently handled supportively for AP with bowel relaxation, intravenous fluids, antiemetics, and ache management elevating the query as as to whether the etiology of pancreatitis was truly drug-induced or idiopathic. .

Our affected person’s historical past of the same episode of AP 2 years in the past in setting using doxycycline extra favors the analysis of DIP because the almost certainly etiology. It additionally scored eight on the Naranjo Adversarial Drug Interplay Scale, revealing a attainable opposed response to doxycycline including to our suspicion of DIP. This case is especially distinctive as there are not any documented circumstances of recurrent pancreatitis on account of doxycycline use to our information.

Varied theories have been proposed to clarify DIP as every class of drug is believed to have a singular mechanism [4]. It’s assumed that tetracyclines may cause DIP both via a poisonous impact mediated by an unknown metabolite or a direct poisonous impact on the pancreas because of the supra-therapeutic bile focus of tetracyclines. [7]. Pharmacological trials with tetracycline confirmed that the focus of bile minocycline was 10 occasions greater than that of the serum, and comparable outcomes have been noticed with tigecycline. [7]. These findings may assist clarify doxycycline-mediated pancreatitis on condition that minocycline and doxycycline are each group 2 tetracyclines and have comparable pharmacokinetic profiles. [8]. Nonetheless, extra analysis is required to clarify the precise pathophysiology of doxycycline-induced pancreatitis.

Conclusions

Doxycycline is a generally prescribed antibiotic and in uncommon circumstances, it will probably trigger DIP as described within the above case. Clinicians ought to concentrate on this potential opposed impact and will keep a excessive diploma of suspiciousness in sufferers who’ve just lately acquired doxycycline and show options suggestive of pancreatitis. DIP is a analysis of alcohol exclusion, gallstones, hypertriglyceridemia, and underlying electrophysiological abnormalities which are first dominated out as attainable causes of pancreatitis within the affected person. Administration constitutes early identification and cessation of the offending agent leading to decision of signs.

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