Tumor necrosis factor-α antagonists: Side effects and their management.

As elevated levels of tumor necrosis factor-alpha (TNF-α) are associated with disease severity in psoriasis and psoriatic arthritis, TNF-α antagonists are being used to treat moderate to severe disease in patients who have contraindications, fail to respond or develop side effects to conventional systemic therapies. It is of utmost importance to be well versed with the possible adverse effects and contraindications of TNF-α antagonists so that they can be used effectively and safely. Many of their adverse effects have been well studied in patients of rheumatoid arthritis (RA) and inflammatory bowel disease (IBD) and may not be completely applicable in psoriasis. This is because patients with RA and IBD are on multiple immunosuppressants while those with psoriasis are mostly receiving single systemic therapy and often have comorbidities that distinguish them from those with RA or IBD. Also, some of the side effects are still controversial and debated. Long-term prospective randomized controlled studies are needed to better understand the associated risk in patients of psoriasis. Baseline screening and periodic monitoring during treatment can reduce and help in early identification and appropriate management of the adverse outcomes. This article reviews the side effects known to be associated with TNF-α antagonists, their pathomechanisms and management guidelines. Some of the common side effects include infusion and injection site reactions, infections particularly reactivation of tuberculosis, autoantibody formation and drug induced lupus erythematosus, liver function abnormalities, hematological, and solid organ malignancies.

A systematic review of the drug-induced Stevens-Johnson syndrome and toxic epidermal necrolysis in Indian population.

BACKGROUND: Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are rare severe cutaneous drug reactions. No large scale epidemiological data are available for this disorder in India. AIMS: To carry out a systematic review of the published evidence of the drug-induced SJS and TEN in Indian population. METHODS: Publications from 1995 to 2011 describing SJS and TEN in Indian population were searched in PubMed, MEDLINE, EMBASE and UK PUBMED Central electronic databases. Data were collected for the causative drugs and other clinical characteristics of SJS and TEN from the selected studies. RESULTS: From 225 references, 10 references were included as per selection criteria. The major causative drugs were antimicrobials (37.27%), anti-epileptics (35.73%) and non-steroidal anti-inflammatory drugs (15.93%). Carbamazepine (18.25%), phenytoin (13.37%), fluoroquinolones (8.48%) and paracetamol (6.17%) were most commonly implicated drugs. Regional differences were observed for fluoroquinolones, sulfa drugs and carbamazepine. Total 62.96% of patients showed systemic complications. Most common complications were ocular (40.29%) and septicemia (17.65%). Higher mortality was observed for TEN as compared to SJS (odd ratio-7.19; 95% confidence interval (CI) 1.62-31.92; p = 0.0023). Observed mortality is higher than expected as per SCORTEN score 3. Duration of hospital stay was significantly higher in TEN (20.6 days; 95% CI 14.4-26.8) as compared to SJS (9.7 days; 95% CI 5.8-13.6; p = 0.020). Cost of management was significantly higher in TEN (Rs. 7910; 95% CI 5672-10147; p < 0.0001) as compared to SJS (Rs 2460; 95% CI 1762-3158). No statistical data were described for steroid use in the studies included. CONCLUSION: Carbamazepine, phenytoin, fluoroquinolones and paracetamol were the major causative drugs. TEN is showing higher mortality, morbidity and economic burden than SJS.

An epidemiological and clinical analysis of cutaneous adverse drug reactions seen in a tertiary hospital in Johor, Malaysia.

BACKGROUND: The prevalence, clinical patterns, and causative drugs of cutaneous adverse drug reactions (cADR) vary among the different populations previously studied. AIM: To determine the prevalence, the clinical patterns of drug eruptions, and the common drugs implicated, particularly in severe cADR such as Stevens-Johnson Syndrome/Toxic epidermal necrolysis (SJS/TEN) and drug rash with eosinophilia and systemic symptoms (DRESS) in our population. METHODS: We analyzed the database established for all cADR seen by the department of Dermatology from January 2001 till December 2010. RESULTS: A total of 362 cADR were seen among 42 170 new clinic attendees, yielding an incidence rate of 0.86%. The most common reaction pattern seen was maculopapular eruption (153 cases) followed by SJS/TEN (110 cases) and DRESS (34 cases). Antibiotics was the most commonly implicated drug group (146 cases) followed by anticonvulsants (81 cases) and antigout drugs (50 cases). The most frequently implicated drug was allopurinol (50 cases). Carbamazepine, allopurinol, and cotrimoxazole were the three main causative drugs of SJS/TEN accounting for 21.8%, 20.9%, and 12.7%, respectively, of the 110 cases seen, whereas DRESS was mainly caused by allopurinol (15 cases). Mortality rates for TEN, SJS, and DRESS were 28.6%, 2.2%, and 5.9%, respectively. CONCLUSIONS: The low rate of cADR with a high proportion of severe reactions observed in this study was probably due to referral bias. Otherwise, the reaction patterns and drugs causing cADR in our population were similar to those seen in other countries. Carbamazepine, allopurinol, and cotrimoxazole were the three main causative drugs of SJS/TEN in our population.

Oral drug provocation test to generate a list of safe drugs: experience with 100 patients.

BACKGROUND: Following a drug eruption, patients and their doctors need to know which drugs can be safely administered for subsequent illnesses. Currently available laboratory tests are unable to answer this question in a clinically meaningful manner. AIMS: To describe our use of oral provocation tests to provide a list of safe drugs to patients. METHODS: We studied the records of 100 patients who underwent oral provocation testing in our department between 2003 and 2009. All patients were admitted to hospital and drugs were administered under supervision, one drug per day. A dermatologist evaluated all symptoms and signs that developed following drug intake. RESULTS: Sixty nine women and 31 men underwent provocation testing. There were 96 reactions in 61 patients, of which 44 reactions in 34 patients were judged to be true reactions. All reactions could be controlled, with treatment or spontaneously. A list of safe drugs was provided to the patient along with written instructions to avoid any drug(s) that had produced a reaction. CONCLUSIONS: Oral provocation tests are safe and effective in providing patients with a list of drugs they can take safely. These tests should preferably be undertaken after admitting the patient to hospital.

Patient-reported multiple drug reactions: clinical profile and results of challenge testing.

BACKGROUND: Some patients report hypersensitivity reactions to many drugs making it difficult to prescribe medications when they fall ill. AIM: To describe the clinical profile of multiple drug hypersensitivity and the results of challenge testing in a large teaching hospital. METHODS: We performed a five-year retrospective review of the records of patients who complained of reactions to two or more unrelated drugs and avoided medication because of a fear of developing reactions. Oral challenge testing was carried out in hospital with drugs suspected by the patient to cause reactions and/or commonly prescribed medications. A positive reaction was diagnosed when symptoms and signs resembled previously experienced episodes and there was no such reaction with placebo. RESULTS: Twenty three patients (aged 14-65 years; 19 females) underwent challenge testing. Their complaints had been present for 1-30 years, with 2-40 drug reaction episodes reported. Antibiotics and non-steroidal anti-inflammatory drugs (NSAIDs) were most commonly implicated, and urticaria/angioedema were the most often reported manifestations. The patients underwent 3-27 challenges with 1-24 drugs. Three had positive challenge reactions with various NSAIDs, 13 developed symptoms and signs that were judged not to be true reactions, and 7 had no reactions. None of our patients qualified for a diagnosis of true multiple drug hypersensitivity. CONCLUSION: Patients who believe they are allergic to multiple, pharmacologically unrelated drugs are usually mistaken. Challenge testing is a reliable way of demonstrating this and providing patients with a list of safe drugs.

Use of clofazimine in dermatology.

Clofazimine is the riminophenazine dye that, due to its antibacterial and anti-inflammatory properties, has been used for several diseases. This article reviews all major characteristics and uses relating to clofazimine, from its pharmacology to its indications in several skin diseases, over and above its classical and well established use in the treatment of leprosy. Due to its anti-inflammatory and antimicrobial properties, clofazimine has a wide spectrum for application in dermatology. The indications include neutrophilic, granulomatous and infectious diseases. Although it is not the first-choice medication in most of the cases, clofazimine should always be considered among the therapeutic options in refractory cases.

Clinical study of cutaneous drug eruptions in 200 patients.

BACKGROUND: Cutaneous drug reactions are the most common adverse reactions attributed to drugs. Any skin disorder can be imitated, induced or aggravated by drugs. AIMS: The present study was carried out to determine the age, sex incidence and clinical pattern of drug eruptions, to recognize offending drugs (self medication or prescribed), to evaluate mortality and morbidity associated with drugs, to educate the patients, and to avoid self-administration of drugs and re-administration of the offending drugs. METHODS: The diagnosis of cutaneous drug reactions is mainly based on detailed history and correlation between drug intake and the onset of rash. Two hundred patients (112 males and 88 females) presenting with cutaneous drug reactions were studied. RESULTS: Fixed drug eruption was seen in 61 patients; others being urticaria and angioedema, morbilliform rash in 37, pruritus in 25, Stevens Johnson (SJ) syndrome in six, purpura in six, exfoliative dermatitis in five, photosensitivity in five, Toxic Epidermal Necrolysis in two, acneiform eruption in three, and erythema multiforme in two patients. The most frequently affected age group was 41-50 years, followed by the 21-30 and 31-40 years age groups. The youngest patient was one year old and the oldest was 80 years old. The period of development of lesions after the intake of drug(s) varies from 01-45 days. Cotrimoxazole was the offending drug in 26 cases, followed by Ibuprofen in 20 cases. CONCLUSIONS: Fixed drug eruption was the most common drug eruption seen. Cotrimoxazole was the most common cause of drug eruptions.

Stevens Johnson syndrome, toxic epidermal necrolysis and SJS-TEN overlap: a retrospective study of causative drugs and clinical outcome.

BACKGROUND AND AIMS: Stevens Johnson syndrome (SJS), toxic epidermal necrolysis (TEN) and SJS-TEN overlap are serious adverse cutaneous drug reactions. Drugs are often implicated in these reactions. METHODS: A retrospective analysis of inpatients' data with these dermatological diagnoses were carried out for three years, to study the causative drugs, clinical outcome, and mortality in these conditions. RESULTS: Thirty patients (15 TEN, nine SJS-TEN overlap, and six SJS) were admitted. In 21 cases, multiple drugs were implicated whereas single drugs were responsible in nine. Anticonvulsants (35.08%) were the most commonly implicated drugs followed by antibiotics (33.33%) and NSAIDS (24.56%). Twenty-five patients recovered whereas five died (four TEN, one SJS-TEN overlap). CONCLUSION: Anticonvulsants, antibiotics and NSAIDs were the most frequently implicated drugs. TEN causes higher mortality than both SJS and SJS-TEN overlap.

Clinical study of cutaneous drug eruptions in 200 patients.

Two hundred patients (112 males and 88 females) with cutaneous drug eruption were studied. The aim was to recognize the offending drug, to evaluate mortality and morbidity, educate the patient and avoid self-administration and readministration of drugs. Fixed drug eruption was the commonest reaction, seen in 61 patients; other reactions being urticaria and angioedema,morbilliform rash in 37, pruritus in 25, Stevens Johnson Syndrome (SJS) in 6, purpura in 6, exfoliative dermatitis in 5,photosensitivity in 5, toxic epidermal necrolysis in 2, acneiform eruption in 3, erythema multiforme in 2. Maximum patients belonged to the age group 41-50, followed by 21-30 and 31-40 years. The youngest was 1 year old and the oldest was 80 years old. Period of development of lesion after intake of drug varied from 1 day to 45 days. Cotrimoxazole was the commonest drug, in 26 cases; followed by Ibuprofen in 20 cases.

Severe dapsone hypersensitivity syndrome.

Dapsone, a potent antiparasitic and anti-inflammatory compound, is mainly used in the treatment of leprosy and a variety of blistering skin diseases. It may cause a severe adverse drug reaction with multiorgan involvement known as dapsone hypersensitivity syndrome. We report the case of a 21-year-old female patient with dapsone hypersensitivity syndrome. The clinical presentation mimicked a viral exanthema.

Carbamazepine--the commonest cause of toxic epidermal necrolysis and Stevens-Johnson syndrome: a study of 7 years.

BACKGROUND: Toxic epidermal necrolysis (TEN) and Stevens-Johnson syndrome (SJS) are a group of severe life threatening drug reactions. The drugs commonly implicated as the cause of these drug reactions vary depending on host factors and the prescription pattern of drugs in that particular area. AIM: The aim of the study was to find the drugs implicated as the cause of SJS/TEN in the patients admitted in the dermatology ward at the Medical College, Thrissur and to find the clinical outcome. METHODS: It was a retrospective study of 7 years from 1997 to 2004. The case records of all patients with a clinical diagnosis of TEN or SJS were studied in detail regarding the drugs implicated as the cause, the management and the clinical outcome. RESULTS: During the study period, 41 patients in the age group ranging from 12 to 72 years were treated as inpatients, of which 20 were males and 21 were females. The commonest drug implicated as the cause of SJS/TEN was carbamazepine (44%). The indication for carbamazepine was control of pain in more than 50% of the cases. Presence of a major systemic disease before the onset of SJS/TEN was associated with a bad prognosis. CONCLUSION: The increased use of carbamazepine, especially for control of pain, may be the reason for the increased incidence of SJS/TEN due to the same drug. Awareness about the drugs implicated in life threatening drug reactions will help physicians in preventing them by judicious use of the drugs.