Escitalopram-Induced Skin Rash: Dermatitis Medicamentosa.

Selective serotonin reuptake inhibitors (SSRI) are the most prescribed antidepressant medications for the treatment of depression and other psychiatric disorders due to their efficacy, tolerability, and safety profile. The dermatological side-effects or cutaneous reactions due to SSRI class of antidepressants is rare. Though there were few case reports of SSRI-induced rash due to fluoxetine, paroxetine, and sertraline, the evidence associated with escitalopram, the highly prescribed antidepressant is comparatively less. The identification and reporting of the drug-related side-effects/adverse drug reactions either serious or non-serious is very important as it will be helpful in understanding, reviewing, and educating the drug-related information before starting medication to the patient. Copyright:

Introduction

The drug-induced cutaneous reactions or drug eruptions can be classified as simple/mild or complex/severe based on risk of morbidity and mortality.[1] Simple drug reactions include exanthem, which usually appear in the 7–10 days after starting of treatment. Drug exanthem is the most common skin reaction to medications that can appear as morbilliform, maculopapular reaction on the skin. Rashes are the most common adverse reaction to medications.[1] Selective serotonin reuptake inhibitors (SSRI) are the most prescribed antidepressant medications for the treatment of depression and other psychiatric disorders due to their efficacy, tolerability, and safety profile.[2] Among the antidepressants, escitalopram is the most prescribed antidepressant followed by sertraline.[3] The most common side-effects of SSRIs include gastrointestinal effects, anxiety, headache, insomnia, movement disorders, and sexual dysfunction. The reported incidence of drug-induced skin reactions due to psychotropic drugs was 0.1% with cutaneous reactions, of which 29% is attributed by antidepressants.[4] The rate of rash/pruritus was the highest with bupropion and the lowest with fluoxetine, paroxetine, sertraline, and venlafaxine—3.7% and <1%, respectively.[4] The skin reactions associated with escitalopram were relatively less reported. Hence, we are reporting a case of drug-induced exanthem secondary to escitalopram in a middle-aged woman.

Case Presentation

A 40-year-old woman was presented to psychiatry outpatient department for complaints of apprehension, decreased interaction, suspiciousness, and forgetfulness of 3 months' duration with no obvious precipitating factor. The above complaints were associated with sleep disturbances and reduced appetite. Her mental status examination revealed poor eye contact with decreased psychomotor activity, laconic speech with increased reaction time, delusion of reference, and blunt affect. She was diagnosed with schizophrenia and started on olanzapine 5 mg daily, which was titrated up to 15 mg per day in the next 4–6 weeks. There was a significant improvement in the above symptoms in the next 2 months, but she started complaining of easy fatigue, low mood, and lack of interest in any previously pleasurable activities, which could be either the negative symptoms or depressive sequelae of schizophrenia. She was started on fluoxetine 20 mg morning dose for the above complaints in the follow-up visit. As she developed side-effects of headache, restlessness that persisted almost every day, she was not willing to take fluoxetine after 2 months, and so was discontinued abruptly. In order to avoid drug interactions, she had been started on Escitalopram 10 mg after 1 month due to persisting depressive symptoms as well as taking into consideration the patient preference. She had no history of any allergies, drug reactions, or any medical illness. She reported that within 1 week of starting the medication, a rash appeared on her face. The patient continued taking escitalopram and observed worsening of the rash on her face in the next 3 days with extension to neck and associated itching. So, she discontinued the medication and observed a mild reduction in itching with no further worsening of rash and came for review. On examination, there was an exanthematous rash with papules and mild localized erythema as shown in Figures 1 and 2. The other areas of skin, oral, and conjunctival mucosa were not affected. There was no associated fever or swelling of the joints or any other tissue involvement. There was mild local raise of temperature with stable vitals and other systematic examination was within normal limits. She had been referred to dermatology department for opinion and treatment of rash. She was diagnosed with drug-induced exanthem and was kept on local steroid ointment and antihistamine medication. The laboratory investigations like complete blood count and liver and renal function tests were performed to find them within normal limits except raised ESR to rule out any organ involvement and severity. There was no history of any recent use of cosmetic products or any local application of creams/lotions on face or food changes or any other medication. The patient reported resolution of the rash and associated itching in the subsequent 2 weeks after complete discontinuation of escitalopram. She did not report any appearance of the rash when she was on fluoxetine 20 mg. As we did not attempt to re-challenge with escitalopram for any reappearance of the rash and based on Naranjo score of 7 for this patient, we considered and reported the suspected drug reaction as probable.[5] Patient's depressive symptoms were managed by psychotherapeutic interventions in the next follow-ups due to poor tolerability to SSRI medications.

Figure 1

Showing erythematous rash over the cheeks and forehead

Figure 2

Showing erythematous maculopapular rash over forehead on day 7

Discussion

The patients' drug history in the past 1 month has to be taken to identify the temporal relationship between drug use and onset of rash. The physical examination along with assessment of type of skin lesions and body surface area involvement helps in reaching the diagnosis of type of drug reactions as well as severity of the drug reaction. The probable drug reaction as per the Naranjo algorithm should be considered if the score is between 5 and 8. The reaction should also be a recognized response to the suspected drug with temporal relation with the drug's use as well as should be confirmed by withdrawal of the drug and could not be explained by the patient's other clinical conditions.[5] The patient's rash was considered drug induced, secondary to escitalopram due to the temporal relation between starting of the drug and occurrence of rash. There were few case reports of SSRI-induced rash with much evidence for sertraline, fluoxetine, and paroxetine, though evidence for escitalopram was less. In one case report, escitalopram was found to cause drug-induced rash and DRESS (drug reaction with eosinophilia and systemic reaction), an adverse drug reaction in other.[6] The mechanisms underlying cutaneous drug reactions can be either immunological or non–immunological mediated or sometimes unknown. The release of mediators of inflammation from mast cells either directly or through IgE-specific antibodies or production and accumulation of toxic metabolites of drugs result in drug reactions.[7] Serotonin is an important mediator of interactions between the neuroendocrine system and the skin. The major source of serotonin in the skin are platelets, which release serotonin upon activation. The released serotonin interacts with the membrane-bound serotonin (5 HT) and serotonin transporter receptors that are present in our skin cells. This interaction of serotonin determines the nature, magnitude, and duration of the cutaneous serotonergic response, that is, either effect or side-effect.[8] One mechanism for SSRI-induced pruritis is found to be mediated through 5-hydroxytryptamine (HT) receptor 7 and TRPA 1 (Transient receptor potential ankyrin 1) ion channel, which was found in animal studies.[9]

Further, the patient had not experienced any adverse skin reaction initially when she was on fluoxetine suggesting that her skin reaction was not SSRI class-dependent. Also, this implies that the escitalopram-specific skin reaction had been possibly due to individual variability.[6] Another probability could be a combination of other drug with propensity to cause skin lesion-like, olanzapine.[10] The class-dependent effect was found with some SSRIs in literature indicating a switch over to non-SSRI drug when a patient had experienced drug reaction. Thus, reporting of the suspected side-effects or adverse drug reactions by the healthcare professionals to the Drug Pharmacopoeia commission and addition of this data to the existing information of the drug is equally important for better understanding of the drug and for providing patient education before prescribing medication.

Conclusions

SSRIs are the most prescribed antidepressant medications due to their efficacy, tolerability, and safety profile. The dermatological side-effects or cutaneous reactions due to SSRI class of antidepressants are rare and there were few case reports of SSRI-induced rash due to fluoxetine, paroxetine, and sertraline in the literature. However, the evidence associated with escitalopram, the highly prescribed antidepressant is comparatively less. The identification and reporting of the drug-related side-effects/adverse drug reactions either serious or non-serious is very important as it will be helpful in understanding, reviewing, and educating the drug-related information.

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.