|Year : 2015 | Volume
| Issue : 1 | Page : 34-36
Chlorpromazine-induced severe exfoliative photoallergic reaction
Saranya Dhanasekaran1, Sujita Kumar Kar2, Suresh Yadav3
1 Department of Psychiatry, National Institute of Mental Health and Allied Sciences, Bangalore, Karnataka, India
2 Department of Psychiatry, King George's Medical University, Lucknow, Uttar Pradesh, India
3 Department of Psychiatry, Lady Hardinge Medical College, New Delhi, India
|Date of Submission||23-Aug-2014|
|Date of Acceptance||20-Sep-2015|
|Date of Web Publication||27-Jan-2015|
Sujita Kumar Kar
Department of Psychiatry, King George's Medical University, Lucknow, Uttar Pradesh
Source of Support: None, Conflict of Interest: None
| Abstract|| |
Despite the availability of newer antipsychotic drugs, chlorpromazine is still widely used due to its cost-utility and effectiveness in many parts of India, particularly for patients in whom marked psychomotor excitement and sleep disturbances are present. The side effects of chlorpromazine include photo-induced skin reactions. Chlorpromazine causes both phototoxic as well as photoallergic cutaneous reactions. We present the case report of an adult male who developed severe photoallergic skin reactions to chlorpromazine. The skin lesions largely resolved on stopping the drug, but reappeared in a more severe form when the drug was inadvertently restarted by the patient. This highlights the need for awareness and education of patients about the skin effects of psychotropics such as chlorpromazine.
Keywords: Chlorpromazine, photoallergic cutaneous reaction, phototoxic reaction
|How to cite this article:|
Dhanasekaran S, Kar SK, Yadav S. Chlorpromazine-induced severe exfoliative photoallergic reaction. Int J Nutr Pharmacol Neurol Dis 2015;5:34-6
|How to cite this URL:|
Dhanasekaran S, Kar SK, Yadav S. Chlorpromazine-induced severe exfoliative photoallergic reaction. Int J Nutr Pharmacol Neurol Dis [serial online] 2015 [cited 2020 Jun 6];5:34-6. Available from: http://www.ijnpnd.com/text.asp?2015/5/1/34/150074
| Introduction|| |
Chlorpromazine was introduced in the mid-1950s as the first antipsychotic. Since then, the first-generation antipsychotics have been largely replaced by atypical second-generation antipsychotics. However, chlorpromazine is still used in clinical practice due to its cost-utility and effectiveness. The side effects of chlorpromazine are many and include photo-induced skin reactions.  Acute phototoxic dermatitis on sun exposure is a well-known side-effect of chlorpromazine administration.  In contrast, little information has been published about the photoallergic skin reactions caused by chlorpromazine. Most of the literature related to the phototoxic/photoallergic reactions of chlorpromazine date between the 1950s and 1980s. ,,,,,
After breakdown, chlorpromazine results in the formation of phenothiazine cation radicals, oxygen-centered radicals, carbon-centered radicals, and sulfur-centered peroxy radicals that are responsible for the photosensitization of the dermis, causing phototoxicity.  In 1981, Kochever reported that chlorpromazine-induced phototoxicity results in damage to the DNA as well as cell membrane  and that superoxides cause the DNA damage.  The photoallergic effect of chlorpromazine is probably due to covalent modification of proteins, which in turn act like antigens, producing an immunological response.  The allergic response induced by chlorpromazine is a form of delayed hypersensitivity reaction, usually developing 24-72 h following exposure to the drug and sunlight, often subsiding after stopping the offending drug, and reappearing after re-exposure to the drug. , In 1967, Satanove and McIntosh reported that phototoxic reactions develop with the 600 mg/day critical dose of chlorpromazine.  However, photoallergic reaction being an immunological response can develop at a lower dose. In a recent study, the incidence of drug-induced cutaneous reaction ranged from 0.1 to 2% in hospitalized patients.  Among the antipsychotics, phenothiazines commonly cause photosensitivity reactions and the incidence of photosensitivity reaction with chlorpromazine is 2-3%. , Photoallergic reactions are relatively rarer entities than phototoxic reactions, though the exact incidence of the same has not been reported. 
| Case report|| |
A 37-year-old male patient diagnosed as a case of undifferentiated schizophrenia presented to the adult psychiatry OPD with scaling eczematous lesions following intake of psychotropic medications. The review of treatment records revealed that the patient had been maintained on 15 mg of olanzapine and 4 mg of risperidone for 2 years when he had an exacerbation of symptoms following missing his medications for 2 weeks. The patient's sleep was impaired, he had auditory hallucinations, and there was marked psychomotor excitement. Following this, he was restarted on olanzapine at a dose of 20 mg/day. However, his psychomotor excitement, sleep disturbance, and irritability continued, for which chlorpromazine was added at a dose of 400 mg/day. After starting the drug treatment (1 day following the initiation of chlorpromazine), he developed erythema and vesiculation over the forehead, cheeks, chin, rim of ears, hands, and feet following sun exposure. These later resulted in desquamation of the skin over his hands, feet, and face. His family members had stopped all medications immediately and sought treatment from a general physician. He was prescribed some local emollients and tablet chlorpheniramine for his itching. His skin lesions resolved in a week's time, without any pigmentation or scarring. However, his psychotic symptoms further worsened. The family sought the advice of a local practitioner who restarted his psychotropic medications. In 3 days, his skin lesions reappeared in the same pattern and he presented at our adult psychiatry OPD. There was no past history of any other significant medical illness. General physical examination had revealed pruritic eczematous lesions over photosensitive areas of his forearms and hands, feet, nape of neck, cheeks, forehead, and pinnae [Figure 1]a-d. The skin over his arms, upper part of legs and thighs, trunk, and shadow regions like philtrum, under surface of chin, and neck were spared. A diagnosis of severe photoallergic reaction to chlorpromazine was made in light of the history and examination findings. Chlorpromazine was stopped immediately and he was prescribed olanzapine at a dose of 20 mg/day along with benzodiazepines for sleep. Avoidance of sun exposure and local ointments with a paraffin base were advised. A skin biopsy could not be done as hospitalization for further evaluation was refused by his family. His lesions resolved in a week's time on stopping chlorpromazine, thus confirming the diagnosis. In the follow-up, the patient remained symptomatic and risperidone at a dose of 4 mg/day was added, to which his psychotic symptoms responded well. His cutaneous lesions resolved completely.
|Figure 1: (a) Severe exfoliative lesion on the palm of both hands. Forearm and the skin over wrist showing scaly lesions. (b) Scaly lesion visible over the dorsum of both hands and forearm, as well as on both feet and legs. (c) Scaly lesion on the right external ear. (d) Scaly lesions over scalp|
Click here to view
| Discussion|| |
Photo-induced drug reactions can occur with chlorpromazine. Photo-induced drug eruptions are cutaneous adverse events caused due to exposure to a drug and either ultraviolet or visible radiation.  Drugs that contain chlorine substituents in their chemical structure, such as chlorpromazine, exhibit photochemical activity leading to free radical reactions with lipids, proteins, and DNA.  These reactions are mostly phototoxic, occur immediately on sun exposure, when reactive oxygen molecules that induce tissue damage are formed. Skin changes resemble sunburn and develop within hours. In contrast, photoallergic reactions are type IV hypersensitivity reactions and are delayed by around 24-72 h after exposure to the offending drug and light. Drug-induced Steven Johnson syndrome/toxic epidermal necrolysis (TEN) is an important differential diagnosis. Steven Johnson syndrome/TEN is a life-threatening cutaneous reaction caused by drugs such as sulphonamides, antibiotics, nonsteroidal anti-inflammatory drugs (NSAIDs), antimalarials, anticonvulsants, allopurinol, antifungals, and antivirals (Nevirapine). , It is a rare cutaneous reaction commonly involving the face, neck, trunk, as well as the mucus membranes and conjunctiva, causing exfoliation of the skin and mucus membrane.  Stopping the offending drug and conservative management to restore the vitals and general condition is the focus of treatment in both skin conditions discussed above. 
One should be cautious enough during initiation of drugs with potential photoallergic properties. The treatment can be started at a lower dose and may be built up later, if the patient tolerates the doses. Starting at a higher dose may be a potential risk factor. In our patient, the starting of chlorpromazine at a higher dose (400 mg/day) may have been one of the factors contributing to the development of a serious photoallergic reaction.
All patients should be psychoeducated about the common and uncommon skin effects of chlorpromazine. Patients should be instructed to avoid direct sunlight or to use sunscreens, especially in the first few weeks following initiation of treatment. , Since most drug-induced photosensitivity reactions are caused by wavelengths within the UV-A range, sunscreens that strongly absorb UV-A should be prescribed. The main goal of treatment of photo-induced drug reactions is to identify the photosensitising agent and to avoid it. In cases where medication cannot be discontinued, patients should be advised to follow sun protection strategies, including wearing sun-protective clothing and using sunscreen.  In most patients, the prognosis is good. Although mortality is rare, drug-induced photosensitivity can cause significant morbidity.
Despite the availability of newer antipsychotic drugs, chlorpromazine is still widely used in many parts of India, particularly for patients in whom marked psychomotor excitement and sleep disturbance are present. Thus, clinicians need to be aware of the adverse effects of chlorpromazine.
| References|| |
Eberlein-König B, Bindl A, Przybilla B. Phototoxic properties of neuroleptic drugs. Dermatology 1997;194:131-5.
Chignell CF, Motten AG, Buettner GR. Photoinduced free radicals from chlorpromazine and related phenothiazines: Relationship to phenothiazine-induced photosensitization. Environ Health Perspect 1985;64:103-10.
Cahn MM, Levy EJ. Ultraviolet light factor in chlorpromazine dermatitis. AMA Arch Derm 1957;75:38-40.
Satanove A, McIntosh JS. Phototoxic reactions induced by high doses of chlorpromazine and thioridazine. JAMA 1967;200:209-12.
Epstein JH, Brunsting LA, Petersen MC, Schwarz BE. A study of photosensitivity occurring with chlorpromazine therapy. J Invest Dermatol 1957;28:329-38.
Blackley RJ. Disappearance of chlorpromazine-induced photosensitivity on substitution of promazine; report on eight cases. Am Pract Dig Treat 1957;8:46-7.
Kochevar IE. Phototoxicity mechanisms: Chlorpromazine photosensitized damage to DNA and cell membranes. J Invest Dermatol 1981;77:59-64.
Harber LC, Baer RL. Classification and characteristics of photoallergy. In: Urbach F, editor. Biologic Effects of Ultraviolet Radiation. Oxford: Pergamon Press; 1969. p. 519-527.
Naldi L, Crotti S. Epidemiology of cutaneous drug-induced reactions. G Ital Dermatol Venereol 2014;149:207-18.
Shields KM. Drug-induced photosensitivity. Pharmacist's letter/prescriber's letter. Available form: http://www.wellnesspharmacy.net/photosensitivity.pdf. [Last accessed on 2014 Sep 16].
Warnock JK, Morris DW. Adverse cutaneous reactions to antipsychotics. Am J Clin Dermatol 2002;3:629-36.
Lee A, Thomson J. Drug-induced skin reactions. In: Lee A, editor. Adverse Drug Reactions. 2 nd
ed. London, UK: Pharmaceutical Press; 2006. p. 125-56.
Drucker AM, Rosen CF. Drug-induced photosensitivity: Culprit drugs, management and prevention. Drug Saf 2011;34:821-37.
Moore DE. Drug-induced cutaneous photosensitivity: Incidence, mechanism, prevention and management. Drug Saf 2002;25:345-72.
Fritsch PO, Sidoroff A. Drug-induced Stevens-Johnson syndrome/toxic epidermal necrolysis. Am J Clin Dermatol 2000;1:349-60.
van Kammen DP, Hurford I, Marder SR. First-Generation Antipsychotics. In: Sadock BJ, Sadock VA, Ruiz P, Kaplan HI, editors. Kaplan and Sadock's Comprehensive Textbook of Psychiatry. 9 th
ed. Vol. 2. Baltimore: Lippincott Williams & Wilkins; 2009. p. 3121.
Marder SR, van Kammen DP. Dopamine receptor antagonists (typical antipsychotics). In: Sadock BJ, Sadock VA, editors. Kaplan and Sadock's Comprehensive Textbook of Psychiatry. 8 th
ed. Vol. 2. Baltimore: Lippincott Williams & Wilkins; 2005. p. 2817.