A Case Report of Isotretinoin: Acute Eosinophilic Pneumonia, A Rare Adverse Reaction

Abstract

This is a case of acute eosinophilic pneumonia (AEP) in a 21-year-old woman with acne vulgaris who was treated with isotretinoin. During treatment, her blood tests showed normal results until the third month, when there was a slight increase in eosinophil count. In the fifth month of treatment, the patient presented to the pulmonology outpatient clinic with complaints of shortness of breath. Lung CT imaging revealed infiltration in both lungs characterized by ground glass opacities. AEP was diagnosed based on blood and imaging results. Isotretinoin therapy was terminated, and oral steroids were initiated, resulting in the improvement of the patient’s symptoms. The patient had no additional risk factors except for smoking, but she had not started or resumed smoking after quitting. This case report highlights the possibility of hypersensitivity pneumonitis following isotretinoin administration.

Introduction

This is a case of isotretinoin-induced acute eosinophilic pneumonia (AEP). Four case reports in the literature have described this rare adverse event. Drug-induced eosinophilic pneumonia is a medical condition whose causes are not yet fully understood. Isotretinoin is a drug linked to AEP.

Case History

A 21-year-old woman with grade 3 acne vulgaris visited the outpatient clinic. Isotretinoin was administered, with her consent, ranging from 0.5 to 1 mg/kg/day based on the patient’s weight, which was 55 kg, starting at 20 mg/day for a conservative approach. Blood tests (liver enzymes, lipid profile and complete blood count (CBC)) performed at the start of therapy were normal. The blood tests remained normal after the first month, and the dosage was increased to 30 mg/day to shorten the treatment duration. After the second month, the patient’s liver enzymes and lipid profile remained normal, but CBC revealed a slight increase in eosinophil count to 0.63 * 10⁹/L. As it was not noticed, the dosage was increased to a maximum dose of 40 mg per day. However, in the fifth month, the patient presented with shortness of breath to the pulmonology outpatient clinic. Lung CT imaging for this presenting condition revealed infiltration in both lungs characterized by ground glass opacities [Figure 1]. A look back at the patient’s blood work during treatment showed a gradual rise in eosinophil count, starting at 0.63 * 10⁹/L in the first month and elevating to 1.08 * 10⁹/L, 1.62 * 10⁹/L and 2.68 * 10⁹/L in the subsequent months, respectively. The patient had no skin manifestations or other abnormal blood test results, indicating DRESS. No involvement of other organs was observed. No evidence of drug abuse, polypharmacy, viral, parasitic, or fungal infections was found. The patient did not report any exposure to toxic gases. There was no indication of allergic respiratory illness, atopy, family history of atopy, or autoimmune disease. The patient had no medical history of the disease. Based on these findings, AEP was diagnosed using eosinophilia and chest CT. The pulmonologist did not perform bronchoalveolar lavage because of its invasiveness. Isotretinoin therapy was terminated, and oral steroids were initiated. The patient’s symptoms improved with the treatment in two weeks, and eosinophilia and infiltration in the chest X-ray resolved within two months. Apart from drug use, smoking was the only identified risk factor. The patient began smoking before treatment. A re-challenge test was not performed because it was unethical. The Naranjo Adverse Drug Reaction (ADR) Probability Scale score was 5. In the post-treatment period, the patient had no further complaints during the four-year follow-up.

Figure 1.

(a and b) Chest CT showing bilateral ground glass opacities

Discussion

AEP is characterized by alveolar epithelial damage and eosinophilic infiltration into lung tissue, mediated by IL-4, IL-5, eotaxin secreted by Th2 lymphocytes and VEGF, IL-33 secreted due to endothelial injury. Despite ongoing research, the precise pathogenesis of AEP remains unclear. The aetiology of this condition encompasses idiopathic origins, as well as associations with infectious agents, toxic substances, smoking and specific pharmaceuticals. Clinical manifestations include fever, dyspnea and cough while imaging via tomography reveals diagnostic but non-specific features, such as a ground-glass appearance, pleural effusion and reticular infiltrates. The standard therapeutic approach involves the administration of oral steroids. Hospitalization with mechanical ventilation and intensive care are necessary in severe cases. The prognosis is excellent and rapid with treatment. Relapse, sequelae and death are unlikely.[1,2] In the idiopathic variant of AEP, diagnosis necessitates a comprehensive evaluation of clinical, radiological and laboratory parameters complemented by an elevated eosinophil count observed in bronchoalveolar lavage or lung biopsy specimens. Although peripheral blood eosinophil levels may be elevated, their diagnostic significance is unclear, as the disease can develop even at normal levels. Drug-induced eosinophilic pneumonia manifests after pharmaceutical use, exhibiting symptom amelioration upon drug cessation and recurrence upon reinstatement. In contrast to the comparatively less emphasized role of blood eosinophils in the smoking-related subtype, the drug-related subtype is distinguished by a more pronounced elevation in the peripheral blood eosinophil count.[2,3]

The first finding in this case was elevated blood eosinophil levels. Subsequently, the patient developed pneumonia with an increase in eosinophil count. After discontinuing the drug and receiving steroid treatment, the patient’s symptoms improved, and there were no additional complaints during the four-year follow-up period. The patient had no additional risk factors except for smoking, but she had not started or resumed smoking after quitting. Smoking-related eosinophilic pneumonia was more likely to occur in individuals who had recently started or quit smoking, with a stronger association observed within the last month.[4]

There were two cases of eosinophilic pneumonia, and two reported cases of eosinophilic pleural effusion that occurred during the use of isotretinoin.[5,6,7,8] There is also a case of eosinophilic esophagitis and gastroenteritis during isotretinoin treatment.[9] Based on the criteria for eosinophilic pneumonia defined in the literature, it can be concluded that isotretinoin use was the initiating factor, whereas smoking did not play a significant role. However, the dose relationship (cumulative or daily dose) remains unclear. This case report highlights the possibility of hypersensitivity pneumonitis following isotretinoin administration.

Key Messages

Isotretinoin may cause drug-related acute eosinophilic pneumonia.

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.