Urticaria and Angioedema Secondary to Methylphenidate Exposure in a Young Child

Design

Case presentation

A 6-year-old Hispanic male presented with symptoms consistent with attention deficit/hyperactivity disorder (ADHD) and was prescribed methylphenidate 2.5 mg daily. Five days after initiation of therapy, the child's mother noted swelling and redness in his left eyelid and around the eye, as well as generalized itching all over the child's body. Additionally, the child had developed a rash over this trunk and both arms.

Methylphenidate was immediately discontinued, as the child was determined to be having an allergic hypersensitivity reaction. Following treatment with antihistamines, symptoms fully resided over the following days.

One week later, the patient was initiated on dexmethylphenidate 2.5 mg daily. The child again developed a similar reaction, including swelling and redness around the eye, but within 24 hours of the first dose. The patient was treated with antihistamines, resulting in resolution of symptoms within the following week.

Study Author Conclusions

This patient developed an allergic adverse reaction in close proximity and subsequent to introduction of methylphenidate, and a similar adverse reaction was reproduced after rechallenge with dexmethylphenidate. There was no history of unusual food ingestion or environmental changes. The abovementioned facts make methylphenidate and dexmethylphenidate the most likely cause.

Methylphenidate causes chronic eosinophilic pneumonia

Design

Case presentation

A 38-year-old male with a past medical history of bronchial asthma (controlled with budesonide/formoterol), glucose-6-phosphate dehydrogenase deficiency, and chronic sinusitis presented with worsening shortness of breath on exertion over the last 3 weeks, interfering with his daily activities. He also reported dry cough; there was no fever, night sweats, upper respiratory tract infections, chest pain, orthopnea, or paroxysmal nocturnal dyspnea.

Chest examination revealed no wheezing or crackles, normal heart sounds, normal jugular venous pressure, no lower limb edema, no signs of connective tissue disease, and no skin rash. Pulmonary function tests were normal, as was his complete blood count. However, his erythrocyte sedimentation rate was 120. Stool samples and toxicology screen were negative.

A chest X-ray revealed bilateral peripheral airspace opacities without mediastinal enlargement and with a normal cardiac shadow. The computed tomography (CT)/high-resolution CT scan showed multiple bilateral peripheral ground-glass attenuations with thickening of the intra- and interlobular septa. Bronchoscopy showed no gross abnormalities, while the bronchoalveolar lavage fluid had a white blood cell count with prominent macrophages at 66%, neutrophils at 5%, eosinophils at 15%, and lymphocytes at 13%. 

Bacterial, tuberculosis, and fungal cultures and stains were negative, as were viral PCR tests. Because numerous eosinophils and macrophages, some of which were multinucleated, were observed in the alveolar spaces, eosinophilic pneumonia was strongly suggested.

Due to starting methylphenidate at the same time as symptom presentation, the patient was diagnosed with eosinophilic pneumonia, most likely caused by methylphenidate. After a 14-day course of prednisolone at 40 mg once daily (gradually tapered over 3 weeks) and methylphenidate cessation, the patient improved. 

At a follow-up appointment 4 weeks later, the patient was doing well with no more dyspnea, normal white blood cell counts, and a normal chest X-ray. 

The patient resumed methylphenidate after experiencing a worsening of his ADHD symptoms. Within a few days, he developed a skin rash, itching, and shortness of breath. The patient was evaluated by a psychiatrist, who discontinued methylphenidate and advised him to avoid using it again. The patient was subsequently started on atomoxetine, a selective norepinephrine reuptake inhibitor, which was well-tolerated without any further complications.

Study Author Conclusions

This is the first case report on oral methylphenidate and the development of chronic eosinophilic pneumonia. The patient developed rash and shortness of breath when re-starting the medication.

The etiology of methylphenidate and eosinophilic adverse reactions (especially pulmonary) is unknown.

Diffuse Maculopapular Rash With Increasing Dosage of Methylphenidate

Design

Case presentation

An 11-year-old male patient was diagnosed with social and generalized anxiety disorder and attention deficit disorder 2 years previously. Initially, the patient was started on sertraline 25 mg daily, which was used for 3 months without any concerns. When sertraline was increased to 50 mg daily, the patient presented with itching and mild skin eruptions on arms and upper chest.

When sertraline was discontinued for 1 month, no skin eruptions or itching were reported. However, the effects were thought to be stress-related, and sertraline was restarted at 50 mg daily with addition of methylphenidate 27 mg daily.

After 1 week of treatment, the patient developed nonpruritic maculopapular skin rash on his face and chest, eventually spreading to his entire body within 1 day. When both medications were discontinued and short-term antihistamine and steroid were initiated, the rash resolved within 10 days. No other medication or unusual foods were reported.

Study Author Conclusions

Because methylphenidateis increasingly used in pediatric populations, clinicians should be familiar with the possibility and nature of methylphenidate-related skin rash. Although present reports are not of life-threatening severity, skin rash may be frightening for the patient and family and impairs treatment compliance.

Desensitization to methylphenidate – The relevance of continued drug intake for a successful outcome

Design

Case presentation

A 7-year-old boy with ADHD and psoriasis developed generalized erythema, pruritus, and fever 5 hours after the first administration of methylphenidate 20 mg. After 2 days, treatment was discontinued with complete resolution of symptoms. No anti-allergy treatment was used.

Four weeks later, methylphenidate was re-challenged; the same clinical symptoms recurred. This was thought to be a non-immediate hypersensitivity. Patch testing (performed by a 20 mg/mL solution) was negative.

Due to lack of suitable alternatives for ADHD (in Portugal), desensitization was proposed. Methylphenidate was administered in increasing doses, 30 minutes apart, over a 6-day period, beginning with a 2-mcg dose of a 0.002 mg/mL solution, until the therapeutic dose of 20 mg/day was reached.

After the therapeutic dose was achieved, the mother interrupted drug intake for 2 days due to misunderstanding the instructions; a mild rash occurred and subsided when another pill was administered.

The desensitization protocol was repeated, and the child remained stable on methylphenidate 20 mg daily 6 months later.

Study Author Conclusions

Successful desensitization of methylphenidate-induced rash

Design

Case presentation

An 8-year-old girl had been suffering from attention-deficit/hyperactivity disorder (ADHD) for 3-4 years prior to visiting being started on methylphenidate 10 mg daily. After 1 week, she developed a pruritic maculopapular rash over the back of her hands, face, chest, abdomen, and legs.

The patient was initiated on an antihistamine, and methylphenidate was discontinued. The rash resolved within a week.

One week later, the drug was rechallenged at a dose of 5 mg daily. Two days later, a similar rash appeared on the patient's face and chest. Again, with discontinuation of the drug, the rash disappeared in 2 days.

Due to poor performance in school without methylphenidate, the patient was initiated on a desensitization protocol, which was successful over a 10-day escalation period.

Study Author Conclusions

This report describes a girl who experienced non-life-threatening cutaneous adverse reactions to methylphenidate.

Desensitization will probably not be helpful in a situation, such as fixed drug eruption and is strongly contraindicated in patients with life-threatening situations, such as erythema multiforme or exfoliative dermatitis. However, the suggested desensitization protocol may enable patients, who had experienced milder cutaneous adverse reactions, to continue taking methylphenidate without developing recurrent reactions.

Fixed drug eruption of the scrotum due to methylphenidate

Design

Case 1

An 8-year-old boy with attention deficit disorder (ADD) presented to the emergency department with two days of severe swelling and redness of the scrotum. The physical examination was unremarkable.

The patient started methylphenidate 10 mg/day 5 days prior. There was no history of allergy or immunologic reaction, and no other drugs had been taken in the past 2 years.

The skin eruption resolved spontaneously 4 days after methylphenidate was discontinued. However, after a re-challenge 2 weeks later, the same skin eruption of the scrotum was documented. Discontinuation of methylphenidate was followed by a complete resolution of the rash in four days.

Macrophage migration-inhibition factor (MIF) assay with methylphenidate was positive.

Case 2

A 10-year-old boy with ADD, treated with methylphenidate 10 mg/day for 7 days, presented to the pediatric emergency department after severe swelling and redness of the scrotum lasting for six hours. The physical examination was unremarkable, and the patient had no history of allergy or immunologic reaction. No other drugs were taken in the past year.

Methylphenidate was discontinued, followed by complete resolution of the rash in three days. Rechallenge with methylphenidate two months later was followed by the same skin eruption of the scrotum within two days. Complete resolution was seen after drug withdrawal.

MIF assay with methylphenidate was positive.

Study Author Conclusions

This paper describes two cases of fixed drug rash induced by methylphenidate. This is suggested to be a rare, but possible, phenomenon. 

The pathogenesis of the fixed drug eruption is unclear, but it is proposed that the drug in the circulatory system may act as a hapten and bind to protein components or receptor cells of the lower dermis. This drug-protein complex is then presented to the lymphocytes by the Langerhans cells in a fashion similar to that occurring in allergic contact dermatitis. The lymphocytes are subsequently stimulated, producing lymphokines that could eventually cause inflammation and damage to cells in the basal cell layer.

MIF, a lymphokine released from sensitized T-lymphocytes by the appropriate antigen, is considered to be a correlate of cell-mediated immunity. Both patients had positive MIF assays, implying a state of immune sensitization toward the offending drug.