Anti-tubercular therapy (ATT) induced exfoliative dermatitis-A case series.

Tuberculosis is a serious contagious disease mainly affecting the lungs and is common in the developing countries. The essential component of all antitubercular regimens include Isoniazid, pyrazinamide as first-line drugs. A serious cutaneous adverse drug reaction namely exfoliative dermatitis (erythroderma) is associated with isoniazid use though uncommon but is common among pyrazinamide users. Here we report 3 cases of tuberculosis patients on antitubercular therapy (ATT) for 8 weeks, came to hospital OP (outpatient) with severe generalized redness and scaling with itching distributed all over the body and trunk. Immediately ATT was discontinued and all the three patients were administered antihistaminic and corticosteroid. The patients recovered within 3 weeks. To confirm ATT induced erythroderma and narrow down the offending agents, sequential rechallenge with ATT was done and again these patients had similar lesions erupt all over the body only with isoniazid and pyrazinamide. Antihistamine, steroids were started and the symptoms resolved and completely recovered within 3 weeks. Prompt withdrawal of the culprit drug along with appropriate medications and supportive measures is necessary for good prognosis. Physicians must be judicious while prescribing ATT especially, isoniazid and pyrazinamide as these can precipitate fatal cutaneous adverse reactions. Strict vigilance may help in early detection of this type ADR and timely management.

The safety and persistence of intravenous iloprost in systemic sclerosis.

INTRODUCTION: Vasculopathy is a crucial feature of systemic sclerosis (SSc). It occurs in almost every patient with SSc, with Raynaud's phenomenon (RP) and digital ulcers (DU) having a great impact on the quality of patients' lives. Intravenous (IV) iloprost, a synthetic analogue of prostacyclin, is broadly used to treat RP and DU secondary to SSc. Currently, there is no standard protocol defined for the iloprost treatment of SSc-associated RP and DU, and, consequently, the management of this treatment is largely based on each centre's experience. OBJECTIVE: The objective of this study is to evaluate the safety profile of a particular scheme of IV iloprost used in our centre as the standard treatment of SSc-related vascular complications. METHODS: We retrospectively evaluated the clinical records of SSc patients, classified according to the 2013 European Alliance of Associations for Rheumatology (EULAR) criteria (31) with SSc-related DU and/or severe RP not responsive to CCB, receiving or who have received IV iloprost infusions from January 1st 2011 to March 31st 2021 Results: Within this time frame, 60 patients (n=44 for DU; n=16 for severe RP) were treated with a monthly 10-hour IV iloprost perfusion with a dosing regimen adapted to individual tolerance. Forty-nine of these 60 patients (81.7%) were on iloprost for more than one year. Within 12 months of therapy, 40 patients have healed the DUs (90.9%), with only 4 patients maintaining active DUs. A significant clinical improvement in RP at 12 months was observed in 87.5% (n=14/16) of SSc patients with severe RP. Eleven AE implying treatment dose/frequency adjustments or suspension were recorded (18.3% of patients): severe headache (n=5), hypotension (n=3), tachycardia (n=1), flushing (n=1) and generalised erythroderma (n=1). In all patients, the perfusion rate was reduced in the following treatment sessions with good tolerance, with the exception of the patient with the generalised erythroderma reaction, who suspended the perfusion and was later switched to bosentan. After a mean follow-up time of 6.9 (+/-) 4.0 years of treatment (range 0.06-22), 24 patients (40%) stopped the therapy, 14 (58.3%) of whom due to clinical improvement. The overall 5-, and 10-year survival rates of IV iloprost were 68.2% and 55.6%, respectively. CONCLUSION: SSc patients who received this flexible IV iloprost regimen achieved clinical improvement, reflected in the high persistence rate of the drug, with a good tolerability profile. In addition, most side effects were mild and easily managed.

Erythrodermic dermatophytosis: an alarming consequence of steroid abuse and misuse. A multicentre prospective study from India.

Erythroderma is usually attributed to some of the commoner causes such as eczematous disorders, psoriasis, malignancies, idiopathic situations and drug-induced scenarios. Rarely, erythroderma has been found to result from dermatophytic infections. Erythrodermic dermatophytosis may be a direct sequel of extensive tinea corporis (with or without a background of topical steroid misuse), paraneoplastic phenomenon, an id reaction or congenital erythrodermic disorders, with subsequent development of dermatophytosis. We present a series of patients who developed erythrodermic dermatophytosis on a background of misuse of steroids.

Erythroderma: An unusual manifestation of imatinib - A rare case report.

Imatinib is a tyrosine kinase inhibitor that selectively inhibits several protein tyrosine kinases which is central to the pathogenesis of human cancer. It forms the first-line treatment for chronic myeloid leukemia (CML) and gastrointestinal stromal tumors. Usually, the drug is well-tolerated with relatively few side effects. Adverse effects most commonly associated with imatinib include mild-to-moderate edema, nausea and vomiting, diarrhea, muscle cramps, and cutaneous reactions. Other side effects such as the elevation of hepatic transaminase and myelosuppression occur less frequently and resolve with interruption of imatinib therapy. Skin rash is one of the most common adverse effects of imatinib incidence of which range from 7% to 88.9%. Exfoliative dermatitis, i.e., erythroderma has been very rarely reported with this drug. We here report a rare case of erythroderma in a patient with CML on imatinib 400 mg/day therapy within 3 months of starting the treatment.

Cutaneous Adverse Events Caused by Sulfonamide-Containing Drugs: Reality or Perception?

The term "sulfa allergy", originally coined for the sulfonamide antibiotics, has become associated with any drugs that contain a sulfonamide moiety. This raises a question: should medicinal chemists avoid making sulfonamide-containing compounds in drug discovery programs? The negative perception of sulfonamides is not supported by any systematic study or data analysis. To address this gap, an analysis of postmarketing reports of cutaneous AEs for drugs with and without a sulfonamide group was conducted. The analysis revealed no evidence of association between the presence of a sulfonamide moiety and a high reporting rate of cutaneous AEs and indicated that the risk of such AEs was associated with the presence of certain structural alerts and higher daily doses. These results strongly suggest that sulfonamide-containing compounds are not at a higher risk of presenting with a cutaneous adverse drug reaction compared with non-sulfonamides and that medicinal chemists should not avoid use of the sulfonamide group.

Levofloxacin-induced Desquamation: A Possible and Rare Case Report.

INTRODUCTION: Levofloxacin is a fluoroquinolone active against both gram-negative and gram-positive bacteria with a well-defined margin of safety and efficacy. It has various labeled adverse effects like other fluoroquinolones but its adverse effect like desquamation is rarely reported. METHODS: We present a case report of levofloxacin-induced desquamation in an Indian patient. CASE REPORT: A-38-year old female patient presented to the outpatient department, with chief complaints of peeling off her epidermal skin. Initially, Desquamation started on her greater finger, which slowly spread to her hand, feet, lower limbs as well as upper limb and neck region. She was prescribed Levofloxacin for respiratory tract infection. RESULTS AND DISCUSSION: Considering temporal relationship, upon causality assessment, (Adverse Drug Reaction) ADR was found to be likely, moderate and probable. The drug was withdrawn along with the initiation of supportive therapy and reaction subsided. CONCLUSION: Although adverse drug reactions like desquamation are not fatal, this induces anxiety in the patients and reduces patient's quality of life. This case report will help keep physicians vigilant about the current adverse drug reaction, helping in the early detection and management of ADR.

Lichenoid drug reaction due to anti-tubercular therapy presenting as erythroderma.

First-line anti-tubercular therapy (ATT) is very effective in management of tuberculosis and is usually well tolerated. Varied spectrum of cutaneous adverse drug reactions is associated with ATT, of which lichenoid drug eruption (LDR) constitutes approximately 10% of the cases. However, LDR presenting as erythroderma is very rare. Here, we report a case of exfoliative dermatitis secondary to LDR which developed after 5 months of ATT.

Keratinocytes apoptosis contributes to crizotinib induced-erythroderma.

Crizotinib is a multi-target receptor tyrosine kinase inhibitor which is of great importance for the management of ALK-rearranged non-small cell lung cancer (NSCLC) patients. Serious erythroderma and toxic epidermal necrolysis have been reported associated with crizotinib treatment. The underlying mechanisms have not been examined. In this study, we tested the toxicity of crizotinib on immortal human keratinocytes (HaCaT) and human primary keratinocytes. We found that crizotinib directly cause cytotoxic on these two cells, which could be the explanation of the clinical characteristic of pathology. Apoptosis was observed and Z-VAD-FMK, a pan-caspase inhibitor can almost totally reverse the apoptosis induction effect of crizotinib. However, mitochondrial dysfunction and DNA damage were not involved in crizotinib-induced apoptosis, indicating the intrinsic apoptosis pathway have no connection with this cutaneous toxicity. Further studies showed that crizotinib significantly increased cleaved-caspase-8, a signaling protein of extrinsic apoptosis pathway, in a concentration and time-dependent manner. Moreover, we found the targets of crizotinib were not involved in HaCaT cells apoptosis. Collectively, our findings first report keratinocytes apoptosis is the key cause of crizotinib-induced cutaneous toxicity. We also reveal crizotinib induce apoptosis through the extrinsic apoptosis pathway due to detected up-regulated cleaved-caspase-8. Meanwhile, the apoptosis is independent of mitochondrial dysfunction, DNA damage and related drug targets inhibition.

Iatrogenic pediatric hydroxocobalamin overdose.

INTRODUCTION: Hydroxocobalamin, a precursor molecule to vitamin B12, has emerged as the preferred empiric treatment for patients rescued from enclosed-space fires with concern for inhalational injury and potential concomitant cyanide toxicity. Limited data exist on the effects of hydroxocobalamin toxicity, particularly in pediatric patients. CASE REPORT: We report a case of a healthy three-year old girl who was rescued from an apartment fire and electively intubated by prehospital providers. Due to concern for potential cyanide toxicity, she received 5 g (373 mg/kg) of intravenous hydroxocobalamin, an amount equivalent to one standard adult dose but over five times the appropriate weight-adjusted dose for this 13.4-kilogram child. On hospital arrival, patient was noted to have chromaturia and diffuse erythroderma without cutaneous burns. She was extubated 4 h after prehospital intubation and discharged home the following morning in good condition with persistent erythroderma. Skin color returned to normal within two days. DISCUSSION: We believe this to be the first reported case of iatrogenic pediatric hydroxocobalamin overdose for the treatment of suspected cyanide toxicity. Erythroderma and chromaturia are expected side effects of hydroxocobalamin, even at therapeutic levels. Along with minor airway burns, the only other finding was a transient and hemodynamically neutral bradycardia, which began shortly after prehospital intubation. As this bradycardia occurred prior to hydroxocobalamin administration, more likely culprits include vagal nerve stimulation from direct laryngoscopy, and sinoatrial muscarinic receptor stimulation caused by repeated doses of succinylcholine. In all, we were unable to appreciate any complications due to excess hydroxocobalamin administration.