Dr. Terencia, Dr. C Jayakumar, Dr. Praveena, Dr. Bhanu vikramam pillai, Dr. Navya
A 15-year-old male, immunized and developmentally normal, was initially evaluated at AIMS for complaints of abdominal pain, altered bowel habits, and weight loss persisting for 6 months. As routine causes of abdominal pain were negative, upper GI endoscopy was done and revealed mild gastritis and a small sliding hiatal hernia. Colonoscopy showed normal results. However, colonoscopy biopsy reports indicated negative results for MTB panel (smear, culture, and GeneXpert) but positive Quantiferon Gold, with a normal CXR. Despite these findings, anti-tuberculosis treatment (ATT) was not initiated, and the patient was observed at home.
As symptoms persisted, diagnostic laparoscopy was attempted. Due to difficulty entering the peritoneal cavity caused adhesions, laparotomy was performed, and an omental biopsy was taken. The omental biopsy reports revealed CB-NAAT positive results, normal AFB smear, AFB c/s showing Mycobacterium tuberculosis complex grown in culture, and HPE showing granulomatous inflammation.
The child was diagnosed with peritoneal TB and started on ATT drugs – INH, rifampicin, and ethambutol. Pyrazinamide was not added initially due to mild transaminitis (SGOT-53/SGPT-34). However, after a normal repeat LFT done one week after adding HRE, pyrazinamide was started after two weeks. Unfortunately, the next day after adding pyrazinamide, the child experienced vomiting and developed itchy maculopapular rashes over the extremities and trunk, leading to admission to a near hospital for treatment with steroids and supportive care.
As symptoms persisted, the child was referred back to AIMS for further evaluation and management. Ok
Differentials
1)DRESS syndrome
2)drug-induced hypersensitivity,
3)viral infections, 4)exanthematous drug eruptions
5)Stevens-Johnson syndrome/toxic epidermal necrolysis
Physical examination revealed pale skin with diffusely spread itchy maculopapular rashes over the trunk and extremities but sparing the face. Systemic examination showed normal findings.
Laboratory investigations showed TC-10.6k with N-62%, L-16.2%, E-14.6%, TSB-0.32, DSB-0.18, SGOT-169.4, SGPT-225.2, ALP-170, and CRP-10mg/L. LFT showed severe transaminitis. Peripheral smear showed normochromic normocytic anemia with moderate eosinophilia and reactive lymphocytes. ATT was immediately stopped, and the possibility of DRESS syndrome versus drug-induced hypersensitivity was considered.
The child was started on IV hydrocortisone, antihistamines, H2 blockers, and other supportive measures. LFT was serially monitored and showed a decreasing trend. Levofloxacin was added initially, and the rashes significantly reduced. ATT was restarted, with rifampicin added first after LFT normalized, followed INH and ethambutol, serially. Steroids were tapered gradually, and the child tolerated ATT well with normalized LFT. The child improved with the given treatment and was discharged with stable vitals.
Pyrizinamide was not added, anticipating it to be the cause of the DRESS syndrome. The child continued on the HRLE (Isoniazid, Rifampicin, Levofloxacin, and Ethambutol) regimen, and the maintenance phase was extended to 8 months as it was a non-pyrazinamide regimen. The child completed 8 months of ATT in total without further reactions with the HRLE regimen.
DRESS SYNDROME:
Drug reaction with eosinophilia and systemic symptoms (DRESS) is a severe adverse drug reaction characterized an extensive skin rash in association with visceral organ involvement, lymphadenopathy, eosinophilia, and atypical lymphocytosis. A clear drug trigger can be identified in the majority of DRESS cases (approximately 80 percent). However, in the remaining 10 to 20 percent, the strength of drug causality is less clear, and in 2 percent of cases, no drug exposure is present.
High-risk drugs for DRESS syndrome include allopurinol, aromatic antiepileptic agents, sulfonamides, vancomycin, minocycline, nevirapine, and antituberculosis agents like rifampicin, ethambutol, isoniazid, and pyrazinamide.
DRESS is estimated to occur in 0.9 to 2 per 100,000 patients per year. In hospitalized patients, DRESS accounts for 10 to 20 percent of all cutaneous adverse drug reactions. The incidence of DRESS in ATT is estimated to be 1 in 1000 to 1 in 10,000 exposures.
Pathogenesis: DRESS is considered a T cell-mediated hypersensitivity reaction with two main pathogenetic mechanisms: drug-specific immune response and human Herpesviridae reactivation with subsequent antiviral immune response.
The latency phase (from drug initiation to onset of reaction) typically ranges from two to eight weeks, although it may be shorter in some cases.
Cutaneous and mucosal manifestations: The eruption starts as a maculopapular eruption that may progress to coalescing erythema. Lesions are symmetrically distributed on the trunk and extremities, with striking facial edema present in the majority of cases.
Systemic symptoms and laboratory abnormalities — Systemic symptoms associated with DRESS include the following
●Fever ≥101.3°F or ≥38.5°C (75 to 90 percent)
●Lymphadenopathy (54 to 65 percent)
●Hematologic abnormalities:
•Eosinophilia >700/microL (82 to 95 percent)
•Leukocytosis (95 percent)
•Neutrophilia (78 percent)
•Lymphocytosis (25 to 52 percent)
•Monocytosis (69 percent)
•Atypical lymphocytes (35 to 67 percent)
●Symptoms and/or laboratory abnormalities related with any visceral involvement (90 percent)
Organ involvement: Most patients with DRESS experience involvement of one or multiple organs, with liver injury being the most common, occurring in up to 90 percent of cases. Acute interstitial nephritis, interstitial pneumonia, and less commonly, myocarditis can also occur.
Criteria to confirm or exclude the diagnosis of DRESS are those included in the Registry of Severe Cutaneous Adverse Reactions (RegiSCAR) scoring system.
TREATMENT-
Identification and withdrawal of the causative drug and supportive treatment are the mainstays of treatment for patients with DRESS. Regular monitoring for organ involvement is warranted. For patients with mild disease without organ involvement or only modest elevation of liver transaminases (<3 times the upper limit of normal), symptomatic treatment of skin inflammation and pruritus with topical corticosteroids is suggested. For patients with severe disease and involvement of the lungs or kidneys, oral glucocorticoids are recommended as first-line therapy. A moderate to high dose (0.5 to 1 mg/kg per day) of prednisolone or prednisone equivalents is given until clinical improvement and normalization of laboratory parameters are achieved. Systemic glucocorticoids should be tapered slowly over 8 to 12 weeks.
TAKE-HOME MESSAGE:
It’s essential to monitor for cutaneous reactions in patients receiving high-risk drugs causing DRESS syndrome. Immediate treatment is crucial, and DRESS survivors should undergo long-term monitoring for the development of autoimmune sequelae..