Introduction

Skin rashes related to drugs are a frequent, undesired side effect.^1,2,3 There are many types of drug eruptions, which range from a clinically mild and unnoticed rash to a severe cutaneous adverse reaction that may be life-threatening. The most common drug eruptions are morbilliform or exanthematous drug eruptions, urticaria and/ or angioedema. Medications can trigger druginduced subacute cutaneous lupus erythematosus.⁴ The quick launch of new medications with no clear comprehension of their pathophysiology can make the diagnosis of drug-induced lupus difficult.⁵ Antipsychotics, previously known as neuroleptics or major tranquilizers, are a class of psychotropic medications that are widely used to manage psychosis in psychiatric patients and have diverse side effects. Many case reports were published regarding skin rashes related to these types of medications, including typical and a typical types.^2,3 Such skin reactions have been reported with typical and a typical antipsychotics, with an estimated prevalence of 5%.⁶ Reports of aripiprazole-induced skin reactions are scant among Gulf Cooperation Council countries, including Kingdom of Bahrain research.⁷ In this report, we present a case of skin rash that developed 10 days after starting Aripiprazole in a male diagnosed with an acute psychotic episode. The significance of this case lies in whether the rash was primarily due to dermatological pathology or due to the side effects of aripiprazole, especially considering that the patient had been placed on several antipsychotics to control his psychosis. The time consumed and the resources required to confirm the main cause of the skin rash are notable, especially as case reports regarding aripiprazole-induced Cutaneous Lupus Erythematosus (CLE) are scarce.⁸

Case presentation

A 38-year-old Bangladeshi male with an unknown history of psychiatric illness and no history of substance abuse was admitted to the acute psychiatry ward with a history of abnormal behavior, talking irrelevantly, believing that he was a secret agent and that there was an electronic chip implanted into his left arm and right buttock with no history of dermatological illness. His complete blood count and urine toxicology screening, thyroid function test, liver function tests, kidney function test, serology/immunology profiles, urea and electrolyte, and a coagulation profile were within normal ranges. The electrocardiogram showed a normal rhythm. A diagnosis of an acute psychotic episode was established. Table 1 presents the medications prescribed from day 0 to 46. He was placed on Risperidone 2 mg at night, and the dose was incremented to 6 mg gradually with no significant improvement. Haloperidol 5 mg was started and increased to 10 mg with a gradual reduction in risperidone doses until discontinuation. He developed extrapyramidal side effects, mainly muscle stiffness, and was placed on Procycledine 15 mg daily with Lorazepam 2 mg. He developed muscle stiffness and had difficulty walking. Haloperidol was discontinued and placed on Aripiprazole (15 mg) and then 30 mg daily. He developed a butterfly rash within 10 days of initiating Aripiprazole treatment and was suspected of having systematic lupus erythematosus (Figures 1 and 2). He was investigated for anti-doublestranded DNA (ds), erythrocyte sedimentation rate (ESR), C-reactive protein, C3, and C4. Anti-nuclear antibodies and all results were within normal ranges (Table 2). A dermatologist was consulted regarding the test results and noted that the patient had a butterfly rash, most likely induced by medication. The dermatologist recommended discontinuing the medication; however, no biopsy was performed. Aripiprazole was discontinued, and the butterfly rash faded gradually until it disappeared after 20 days of discontinuation (Figure 3). He was placed on olanzapine with a total dose of 15 mg daily, and his condition improved with no extrapyramidal side effects. He developed depressive features, and his mood improved with Bupropion 300 mg daily.

Discussion

The case had been a challenge for the medical team due to the slow improvement in his psychosis and the muscle stiffness due to the side effects of medications. Aripiprazole is an antipsychotic medication and a member of the benzisoxazole group.⁹ It is considered an atypical member of antipsychotics, a class of dopaminergic system stabilizers.^3,10 Also, it is considered to be a thirdgeneration antipsychotic. It is a D2 receptor, 5 HT1a partial agonist, and 5 HT2 antagonists that equilibrate dopaminergic and serotonergic systems.^4,10 Many cases of skin pathologies associated with Aripiprazole use have been reported, including both oral and intramuscular formulations.² Medications linked to drug-induced lupus erythematosus have many chemical structures, including aromatic amines and benzisoxazole has aromatic rings.^5,11 The mechanism related to drug-induced lupus erythematosus involves genetic factors, drug biotransformation, and epigenetic dysregulation in the immune system.^5,4 Drug-induced skin rashes are known to occur within 7 to 14 days of starting the drug and fade within the same time frame upon discontinuing the medication. Drug skin reactions occur in hospitalized patients, with incidents ranging from 1 to 3%.¹² Discontinuing the medication is important in identifying the offending agent.^13,4 Skin drug reactions may be defined, excluding other reasons for skin eruptions; improvement after discontinuing the medication and associating skin reactions with medication is known.³ In our case, investigations were done to exclude lupus erythematosus, and it came out negative, and the butterfly rash faded after discontinuing the medications within 2 weeks. Aripiprazole was noted to induce alopecia, photosensitivity, rash, and hyperhidrosis; in our case, butterfly rash was noted.² Compared to published case reports of aripiprazole-induced rashes, the clinical features were strikingly similar to CLE, with the butterfly rash presentation in this patient. This prompted the treating team to investigate the possibility of systemic lupus erythematosus (SLE), but the symptoms subsided after discontinuing the offending drug, aripiprazole.

Conclusion

Aripiprazole, in our case, was the most probable cause for cutaneous lupus skin reaction as ANA was negative, and many case reports were published regarding aripiprazole-induced skin reactions. Other causes of skin reactions should be considered, including medical pathologies and environmental factors. The significance of this study lies in the fact that lupus rash is not listed as a known side effect of Aripiprazole. The team conducted thorough investigations and consultations to confirm that the medication was the cause of the reaction, as discontinuation was not a preferred option. The patient had previously experienced multiple treatment changes, all of which resulted in severe side effects. Additionally, altering the treatment again would further delay the management of his psychosis.

It is crucial to alert the medical community about serious events and the role of observation as evidence like the risks of skin reactions related to Aripiprazole in order to take the best course of action to treat skin condition-related side effects and to place medication-induced lupus as a differential diagnosis in such cases.

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Conflicts of interest

There is no conflict of interest