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CORRESPONDENCE
Year : 2022  |  Volume : 67  |  Issue : 6  |  Page : 781-783
Isotretinoin induced pancreatitis: A rare idiosyncratic reaction


From the Department of Dermatology and STD, V.M.M.C. and Safdarjung Hospital, Delhi, India

Date of Web Publication23-Feb-2023

Correspondence Address:
Niharika Dhattarwal
From the Department of Dermatology and STD, V.M.M.C. and Safdarjung Hospital, Delhi
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/ijd.ijd_206_22

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How to cite this article:
Dhattarwal N, Khunger N, Lal A. Isotretinoin induced pancreatitis: A rare idiosyncratic reaction. Indian J Dermatol 2022;67:781-3

How to cite this URL:
Dhattarwal N, Khunger N, Lal A. Isotretinoin induced pancreatitis: A rare idiosyncratic reaction. Indian J Dermatol [serial online] 2022 [cited 2023 Mar 31];67:781-3. Available from: https://www.e-ijd.org/text.asp?2022/67/6/781/370280




Sir,

Isotretinoin (also known as 13-cis-retinoic acid) is a medication that is commonly prescribed for treating severe acne. Adverse effects of isotretinoin such as cheilitis and xerosis are common and the teratogenic effect is well known, whereas acute pancreatitis is a rarely documented serious adverse effect. Isotretinoin-induced pancreatitis may either be idiosyncratic or due to elevated triglycerides (usually when >500 mg/dl).[1] The course is usually mild with good prognosis, but it is vital to recognise the signs and symptoms early and stop the offending agent in a timely manner. In this study, we describe this rare but potentially fatal side effect and its management in an 18-year-old woman who was prescribed isotretinoin for acne vulgaris.

An 18-year-old woman weighing 49 kg presented with grade 4 nodulocystic acne and was started on isotretinoin 20 mg following normal baseline investigations including liver function tests and lipid profile [Table 1]. After 2 weeks, the patient developed abdominal pain mainly in the epigastric location, radiating to her back which was severe in intensity and constant in nature. On examination, there was tenderness on palpation, but no guarding or rigidity. The patient was referred to the physician and diagnosed with acute pancreatitis with raised serum amylase levels of 174 U/ml. Ultrasound of the abdomen was inconclusive. Triglycerides showed four times rise from baseline levels but <500 mg/dl whereas liver function tests remained normal [Table 1]. Diagnosis of the drug-induced idiosyncratic pancreatitis was made after ruling out other aetiologies. Isotretinoin was discontinued and the patient was treated with bowel rest, intravenous fluids and analgesics for pain after which both amylase levels and triglycerides returned to normal levels within 2 weeks [Table 1]. Acne lesions were treated with antibiotics, anti-inflammatory agents and intralesional triamcinolone 10 mg/ml and gentamicin 40 mg/ml in 1:4 dilution for cystic lesions. The patient improved [Figure 1], [Figure 2], [Figure 3] and is under regular follow-up.
Table 1: Laboratory parameters during the course of disease

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Figure 1: An 18-year-old woman with nodulocystic acne

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Figure 2: An 18-year-old woman who developed isotretinoin-induced pancreatitis managed with combination of antibiotics, anti-inflammatory and intralesional agents

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Figure 3: An 18-year-old woman who developed isotretinoin-induced pancreatitis after 2 weeks of treatment

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Isotretinoin is associated with wide array of side effects; common being cheilitis, dryness of the skin, photosensitivity, photophobia, paronychia, arthralgia, myalgia, headache, etc., and potentially serious side effects like teratogenicity, reduced night vision, hyperlipidaemia, pancreatitis, hepatic dysfunction, depression, etc. Pancreatitis secondary to isotretinoin could be due to two reasons: hypertriglyceridaemia and idiosyncratic reaction. The exact cause of lipid elevation by isotretinoin is not known. However, it is hypothesised that retinoid–albumin interaction in plasma displaces the triglyceride from albumin, causing its elevation. Other proposed hypothesis is interaction of isotretinoin with some essential proteins or enzymes of lipid metabolism like hydroxymethylglutaryl reductase.[2] This natural history of triglyceride elevation while on isotretinoin is predictable to some extent but not considered at risk for hypertriglyceridaemia-associated pancreatitis unless above >500 mg/dl (fasting).[1] Recent guidelines by the Endocrine Society Clinical Guidelines Subcommittee consider this risk at even higher values of >2000 mg/dl (fasting).[3] In a retrospective trial of patients taking isotretinoin, the incidence of lipid disorders, including hypertriglyceridaemia, was up to 3.11%, however there was no report of acute pancreatitis.[4] Hypertriglyceridaemia-associated pancreatitis is rare with only five cases reported so far.[1],[2],[5] Four out of these five patients whose data were available, had elevated baseline triglyceride levels and had been on treatment for ≥4 weeks. All five patients were aged >35 years. Idiosyncratic pancreatitis as seen in our case is also uncommon with 21 cases reported previously. Unlike hypertriglyceridaemia-associated pancreatitis, there is no predictable pattern such as older age or baseline elevated triglyceride levels. The time that patients were on isotretinoin before developing idiosyncratic pancreatitis ranged from 10 days to 1 year. While triglyceride-induced pancreatitis can be monitored with serial triglyceride levels, idiosyncratic isotretinoin-induced pancreatitis is highly unpredictable or preventable. Therefore, it is important to keep a high index of suspicion for this rare serious complication when any patient reports of abdominal pain while on isotretinoin therapy. Drug-induced pancreatitis runs a relatively mild course with good prognosis and low mortality, but timely stoppage of offending agent is essential.

To conclude, isotretinoin is a highly efficacious drug for acne vulgaris but with many potential side effects. The occurrence of this rare side effect of pancreatitis highlights the importance of dermatologists being vigilant on all drug-related complications, which often begin with simple ailments like abdominal pain but can eventually prove to be life threatening.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
   References Top

1.
Opel D, Kramer ON, Chevalier M, Bigby M, Albrecht J. Not every patient needs a triglyceride check, but all can get pancreatitis: A systematic review and clinical characterization of isotretinoin-associated pancreatitis. Br J Dermatol 2017;177:960-6.  Back to cited text no. 1
    
2.
Atiq MU, Raza A, Ashfaq A. Idiosyncratic reaction causing a rare side effect: Isotretenoin-induced pancreatitis. Cureus 2019;11:e6102.  Back to cited text no. 2
    
3.
Berglund L, Brunzell JD, Goldberg AC, Goldberg IJ, Sacks F, Murad MH. Evaluation and treatment of hypertriglyceridemia: An Endocrine Society clinical practice guideline. J Clin Endocrinol Metab 2012;97:2969-89.  Back to cited text no. 3
    
4.
Brzezinski P, Borowska K, Chiriac A, Smigielski J. Adverse effects of isotretinoin: A large, retrospective review. Dermatol Ther 2017;30:4.  Back to cited text no. 4
    
5.
Ashraf M. Acute pancreatitis caused by isotretinoin. Cureus 2020;12:e8710.  Back to cited text no. 5
    


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