Drug Reaction With Eosinophilia And Systemic Symptoms Research Articles

Dermatologic Emergencies CME Part III: Drug reactions

This section reviews the triad of life-threatening drug reactions including Stevens-Johnson/toxic epidermal necrolysis (SJS/TEN), drug reaction with eosinophilia and systemic symptoms (DRESS), and acute generalized exanthematous pustulosis (AGEP).

Viral infections and drug hypersensitivity.

Virus infections and T-cell-mediated drug hypersensitivity reactions (DHR) can influence each other. In most instances, systemic virus infections appear first. They may prime the reactivity to drugs in two ways: First, by virus-induced second signals: certain drugs like β-lactam antibiotics are haptens and covalently bind to various soluble and tissue proteins, thereby forming novel antigens. Under homeostatic conditions, these neo-antigens do not induce an immune reaction, probably because co-stimulation is missing. During a virus infection, the hapten-modified peptides are presented in an immune-stimulatory environment with co-stimulation. A drug-specific immune reaction may develop and manifest as exanthema. Second, by increased pharmacological interactions with immune receptors (p-i): drugs tend to bind to proteins and may even bind to immune receptors. Without viral infections, this low affine binding may be insufficient to elicit T-cell activation. During a viral infection, immune receptors are more abundantly expressed and allow more interactions to occur. This increases the overall avidity of p-i reactions and may even be sufficient for T-cell activation and symptoms. There is a situation where the virus-DHR sequence of events is inversed: in drug reaction with eosinophilia and systemic symptoms (DRESS), a severe DHR can precede reactivation and viremia of various herpes viruses. One could explain this phenomenon by the massive p-i mediated immune stimulation during acute DRESS, which coincidentally activates many herpes virus-specific T cells. Through p-i stimulation, they develop a cytotoxic activity by killing herpes peptide-expressing cells and releasing herpes viruses. These concepts could explain the often transient nature of DHR occurring during viral infections and the often asymptomatic herpes-virus viraemia after DRESS.

HLA-A*32:01 ASSOCIATED VANCOMYCIN-INDUCED DRESS SYNDROME AND DESQUAMATION IN AN AFRICAN AMERICAN WOMAN

<h3>Introduction</h3> Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) Syndrome is a severe, life-threatening drug reaction. We present a patient with a desquamating rash ultimately diagnosed as DRESS syndrome due to vancomycin. The three candidates for this drug-induced rash were vancomycin, cefepime, and apixaban <h3>Case Description</h3> A 54 year-old African American woman developed fever and erythematous rash involving her lips, face, arms, and abdomen. She received her first dose of apixaban that day and had completed a 25-day course of cefepime and vancomycin the day previous. The patient was febrile to 102.7 and experienced nausea and vomiting. Her rash progressed from erythematous to desquamative during her hospitalization. Her eosinophil count peaked at 3200, creatinine to 5.1, AST/ALT 554/308 respectively. Biopsy was obtained and consistent with drug eruption. HLA-A*32:01 testing was positive. Her RegiSCAR score was 6 based on her fever, eosinophilia, rash, organ involvement, biopsy, and exclusion of other causes via negative CMV, EBV, HIV and blood cultures. Her eosinophil count promptly dropped to zero after prednisone administration, and her rash slowly healed with aggressive care. She was medically stabilized and discharged to post-acute care on a steroid taper. <h3>Discussion</h3> This patient presentation posed an interesting clinical challenge, requiring differentiation between a type I hypersensitivity reaction to apixaban versus a type IV DRESS reaction. Her HLA positivity and RegiSCAR score ultimately helped clinch the diagnosis of vancomycin-induced DRESS. HLA-A*32:01 is associated with vancomycin-induced DRESS in people of European descent; perhaps the association occurs independently of race and ethnicity.

A NOVEL CASE OF DRUG REACTION WITH EOSINOPHILIA AND SYSTEMIC SYMPTOMS (DRESS) AFTER METOLAZONE USE

<h3>Introduction</h3> Drug reaction with eosinophilia and systemic symptoms (DRESS) is a rare but potentially lethal delayed hypersensitivity reaction often triggered by high-risk drugs such as antiepileptics and antibiotics containing sulfonamides. To our knowledge, there are no reported cases of metolazone, a sulfonamide containing, thiazide diuretic as the causative agent of DRESS. Here we present a case of DRESS after metolazone usage. <h3>Case Description</h3> n.18-year-old male with a history of focal segmental glomerulosclerosis (FSGS) presented with rash, lower extremity edema and fatigue. On exam, the patient demonstrated an extensive hyperpigmented, macular, pruritic rash involving the abdomen, back, arms and legs. Initial labs demonstrated a leukocytosis of 16.5 × 10³/uL; 7.9 × 10³/uL eosinophils; and a worsening AKI with a creatinine of 3.88 mg/dL, which was 1.97 mg/dL 21-days prior. Four weeks before presentation, the patient had been initiated on metolazone for his underlying kidney disease. As a result, DRESS was suspected, and the patient was started on high dose prednisone with future doses of his metolazone held. Over the next several days, the patient's eosinophilia resolved and his rash and creatinine improved. <h3>Discussion</h3> Most cases of DRESS are caused by antibiotics and antiepileptic medications- thiazide diuretics are rarely implicated in the disease. Here we present a unique case of DRESS caused by metolazone. Clinicians should maintain a high index of suspicion for the disease when patient's present with multi-organ dysfunction, rash, and leukocytosis with eosinophilia in the setting of metolazone use.

PARANOID ABOUT RASHES: OLANZAPINE INDUCED DRUG REACTION WITH EOSINOPHILIA AND SYSTEMIC SYMPTOMS

<h3>Introduction</h3> Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) is a severe adverse reaction caused by more than 50 prescription drugs. Although antiepileptics and antibiotics account for most cases, the variety of potential drug classes can make identifying the causative agent challenging. <h3>Case Description</h3> Thirty-year-old male was initially admitted to the medical ICU for treatment of alcoholic hepatitis. Hospital course was complicated by an upper GI bleed, hepatic encephalopathy, respiratory failure, and multiple infections requiring repeated courses of antibiotics. Two months into the hospital stay, he developed a diffuse pruritic maculopapular rash that progressed to cover his trunk, neck and extremities. Workup revealed elevated aminotransferases along with worsening creatinine, leukocytosis, and eosinophilia concerning for DRESS. Medication review revealed the patient received several days of vancomycin in addition to a month-long course of olanzapine for paranoia suffered while inpatient. Patient first received olanzapine 8 weeks prior to symptom onset. HLA-A*32:01 was obtained and negative. Topical steroids were applied, and potential offending medications held. Rash resolved over the next few weeks followed by clinical improvement. Olanzapine was added to the allergy list to avoid future episodes. <h3>Discussion</h3> The diagnosis of DRESS can be challenging as it often occurs in the inpatient setting with patients exposed to varying amounts of multiple drugs, including less common agents such as olanzapine. When multiple culprit drugs have been administered, evaluating factors such as timeline of exposure and genetic predisposition may be helpful in identifying the cause. This can lead to prompt removal of the offending drug minimizing morbidity and mortality.

A CASE SERIES OF HLA-B*58:01 SPECIFIC ALLOPURINOL-INDUCED DRESS/DIHS

<h3>Introduction</h3> Drug reaction with eosinophilia and systemic symptoms (DRESS)/drug-induced hypersensitivity syndrome (DIHS) represents a severe adverse drug reaction with a high mortality rate. Allopurinol-induced DRESS/DIHS can be associated with polymorphisms in human leukocyte antigen (HLA) genes, with higher prevalence of the HLA-B*58:01 allele in Asians (7.4%) and Africans (3.8%) compared to other ethnic populations. <h3>Case Description</h3> We report four cases (two of African and two of Asian descent) of severe allopurinol-induced DRESS/DIHS requiring hospitalization for treatment. All patients presented with a generalized, erythematous dermatitis and peripheral eosinophilia after recently starting allopurinol. RegiSCAR scoring ranged from 7-8. All cases were HLA-B*58:01 positive with skin punch biopsies consistent with DRESS/DIHS. Two patients had mucocutaneous involvement, while three had notable organ involvement and relapse of disease after tapering immunosuppressant therapies. Half of the patients had evidence of viral reactivation. One patient succumbed to infectious pulmonary complications and cyclosporine toxicity. Table 1 summarizes the characteristics, laboratory findings and clinical courses of these cases. <h3>Discussion</h3> Our case series demonstrated two African and two Asian patients with severe allopurinol-induced DRESS/DIHS with positive HLA-B*58:01 genotyping. This allele has been associated with an increased risk of DRESS/DIHS from allopurinol. Detection of HLA*58:01 has higher prevalence in Asians and Africans and may portend worse disease. Recent guidelines recommend screening for the HLA*58:01 allele in Southeast Asian and African patients prior to initiation of allopurinol. Our case series highlights the importance of recognizing populations with high HLA-B*58:01 allele frequency before introduction of allopurinol to prevent DRESS/DIHS.

ERYTHRODERMA AND EOSINOPHILIA WITH MULTI-SYSTEM INVOLVEMENT, A CASE OF VRESS

<h3>Introduction</h3> Resembling Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS), Virus Reactivation with Eosinophilia and Systemic Symptoms (VRESS) occurs triggered by members of Herpesviridae family viruses. <h3>Case Description</h3> A 12-year-old male was hospitalized with a 5-day history of fever, pruritic erythematous rash on the trunk and extremities, and facial edema. The patient was exposed to a cousin diagnosed with Multisystem Inflammatory Syndrome in Children (MIS-C) 10 days prior. No history of traveling, unusual food intake, URI, drug ingestion during the prior 3 months. Patient was treated with clindamycin x 10 days for possible Staphylococcal Scalded Skin Syndrome. Patient was noted to have eosinophilia of >2000 that persisted through the hospital course and thereafter, transaminitis with direct bilirubinemia, transient microscopic hematuria, elevated CRP and C3, normal EKG and chest radiograph, normal T/B/NKC counts, normal levels of immunoglobulins and elevated IgE (2163>1579IU/mL). IgG and IgM were negative for: CMV, adenovirus, strongyloidces, HAV, HBV, and HIV. IgG positive to: EBV, HHV-6, mycoplasma, HHV-6, HSV1, and parvovirus. Negative cultures for MRSA and group A Streptococcus. Negative PCRs for COVID -19. At 8 week follow up, skin erythema evolved into desquamation in the fingers and eosinophilia persisted. <h3>Discussion</h3> VRESS should be on the differential for patients presenting with a DRESS-like symptoms in the absence of drug exposures. VRESS is often triggered by members of the Herpesviridae family of viruses including EBV and HHV-6, to both of which this patient was exposed to in the past. While diagnosis is one of exclusion, early identification can guide appropriate management.

(131) Lamotrigine-induced Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) Exacerbated by COVID-19 Infection

(131) Lamotrigine-induced Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) Exacerbated by COVID-19 Infection

PSUN62 A Rare Case of Atorvastatin Induced Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) Syndrome - A Case Report.

Abstract Clinical Case A 77 year-old female presented to emergency department with progressively worsening rash that started one week ago. On physical examination blanching erythema was noted in lower back, buttocks and extremities. There was no desquamation or involvement of oral mucosa. No lymphadenopathy or hepatosplenomegaly was noted. Laboratory investigations showed white blood cell count of 21.2×10^3/uL, with 33.1% eosinophils. Creatinine was elevated at 2.8mg/dL from baseline of 0.8mg/dL. Further lab work revealed alkaline phosphate 2314 IU/L, aspartate transaminase 587 IU/L, and alanine transaminase 620 U/L, total bilirubin 7.3mg/dL with direct bilirubin of 5.1mg/dL, Immunoglobulin E level of 2000 IU/ml and normal Tryptase levels. Serology for viral hepatitis, Epstein-Barr virus, Cytomegalovirus and Human immunodeficiency virus was negative. Autoimmune workup including antinuclear Antibody (ANA), anti-neutrophil cytoplasmic antibody (ANCA), mitochondrial antibody, smooth muscle antibody, double stranded DNA, anti-histone antibody, rheumatoid factor, Sjogren's antibody and centromere antibody were negative. Urinalysis, urine protein electrophoresis and serum protein electrophoresis were also normal. Computed tomography (CT) scan of chest showed mild supraclavicular and mediastinal lymphadenopathy. Review of medical records revealed that patient was recently discharged from hospital with a prescription of Atorvastatin following admission for transient ischemic attack 6 weeks ago. Skin biopsy showed superficial perivascular dermatitis with extravasation of red blood cells with no diagnostic evidence of vasculitis, granuloma or malignancy. Based on biopsy findings, recent drug administration followed by appearance of rash, hematological abnormality, lymphadenopathy and multi-system involvement and after exclusion of other possible causes, diagnosis of DRESS syndrome was made. Atorvastatin was held and patient was given Methylprednisolone for three days followed by Prednisone 1mg/kg with taper. Rash as well as kidney and liver functions improved drastically within two days. Discussion Our patient presented with one week of rash associated with deteriorating kidney and liver functions. Atorvastatin was initiated five weeks prior to development of rash. All the possible infectious etiologies and malignancy was ruled out based on the laboratory work mentioned above. Work up for vasculitis was also negative. DRESS syndrome is a late onset drug induced hypersensitivity reaction which usually manifests 3 weeks to months after the offending drug is started. It is very rare with an incidence of 0.9-2 per 100,000 patients per year and accounts for 10-20% of all cutaneous adverse drug reactions. DRESS syndrome if untreated carries significant risk of mortality, between 10-20%. RegiSCAR (European Registry of Severe Cutaneous Adverse Reaction) scoring system can be used to help diagnose DRESS syndrome. It takes into account multiple factors including fever, lymphadenopathy, eosinophilia, rash, number of organs involved, disease duration, skin biopsy findings and negative results of investigations to rule out alternate causes of patient's symptoms. Patient responded well to systemic steroids followed by oral steroids with taper. Presentation: Sunday, June 12, 2022 12:30 p.m. - 2:30 p.m.

Female Patient with Ceftriaxone-Induced Drug Eruption with Eosinophilia and Systemic Symptoms in Second Level Care. Case Report

Drug reaction with eosinophilia and systemic symptoms (DRESS) is a hypersensitivity reaction. Therefore, the case of a 51-year-old woman with no history of drug allergies is presented. In empirical treatment with Ceftriaxone, presenting 15 days later pruritic maculopapular rash on the chest, abdomen and extremities accompanied by temperature rises of up to 39°C. Laboratories with leukocytes of 47.38/uL, with eosinophils of 27.07/uL, and skin biopsy report with inflammatory infiltrate in the dermis at the expense of eosinophils. regiSCAR and J-SCAR with results of 8 and 6 points respectively. Administering methylprednisolone 250 mg every 24 hours for 3 days, continuing with prednisone 50 mg per day. Improvement of skin lesions and laboratory abnormalities at 72 hours. DRESS induced by this antibiotic is rare. Appropriate assessment of the indications and diagnostic assumption of side effects is important because the manifestations are potentially reversible.of rash, fever, facial edema, lymphadenopathy, hematologic abnormalities, and visceral involvement.

LTT and HLA testing as diagnostic tools in Spanish vancomycin-induced DRESS cases: A case-control study.

Drug reaction with eosinophilia and systemic symptoms (DRESS) is a severe T-cell-mediated off-target adverse reaction. DRESS cases caused by vancomycin have often been reported. The HLA-A*32:01 allele has been associated with genetic susceptibility to vancomycin-induced DRESS in US citizens of European descent. We have analyzed the association of the HLA-A*32:01 allele in 14 Spanish DRESS cases in which vancomycin was suspected as the culprit drug, and the lymphocyte transformation test (LTT) as an in vitro assay to evaluate vancomycin sensitization. The results were compared to vancomycin-tolerant control donors. LTT was performed in 12 DRESS cases with PBMCs from resolution samples available and in a group of 12 tolerant donors. ROC curves determined that LTT is a suitable tool to identify patients sensitized to vancomycin (AUC = 0.9646; p < 0.0001). When a stimulation index >3 was regarded as a positive result, contingency tables determined 91% sensitivity, 91.67% specificity, 91% positive predictive value, and 91.67% negative predictive value (p = 0.0001, Fisher's exact test). The HLA A*32:01 allele was determined by an allele-specific PCR assay in 14 cases and 25 tolerant controls. Among the DRESS cases, five carriers were identified (35.7%), while it was detected in only one (4%) of the tolerant donors, [odds ratio (OR) = 13.33; 95% CI: 1.364-130.3; p = 0.016]. The strength of the association increased when only cases with positive LTT to vancomycin were considered (OR = 24.0; 95% CI: 2.28-252.6; p = 4.0 × 10-3). Our results confirm the association of the risk allele HLA-A*32:01 with vancomycin-induced DRESS in Spanish cases, and support LTT as a reliable tool to determine vancomycin sensitization.

Predicting DRESS Syndrome Recurrence—The ReDRESS Score

This cross-sectional study of DRESS syndrome cases creates a model capable of predicting recurrence to identify patients most at risk.

Tools to improve the diagnosis and management of T-cell mediated adverse drug reactions.

Delayed drug T-cell immune-mediated hypersensitivity reactions have a large clinical heterogeneity varying from mild maculopapular exanthema (MPE) to severe cutaneous adverse reactions (SCARs) such as acute generalized exanthematous pustulosis (AGEP), drug reaction with eosinophilia and systemic symptoms (DRESS) and severe skin necrosis and blistering as seen in Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN). Given the knowledge gaps related to the immunopathogenesis of these conditions, the absence of validated diagnostic tools and the significant associated morbidity and mortality, patients with SCARs often have limited drug choices. We performed a comprehensive review aiming to evaluate in vivo diagnostic tools such as delayed intradermal skin and patch testing and ex vivo/in vitro research assays such as the lymphocyte transformation test (LTT) and the enzyme-linked ImmunoSpot (ELISpot) assay. We searched through PubMed using the terms “drug allergy,” “in vivo” and “ex vivo” for original papers in the last 10 years. A detailed meticulous approach adapted to the various clinical phenotypes is recommended for the diagnostic and management of delayed drug hypersensitivity reactions. This review highlights the current diagnostic tools for the delayed drug hypersensitivity phenotypes.

Erratum for the article “DRESS syndrome on the background of adding meropenem to carbamazepine therapy: a clinical case”

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A Shorter Time to Drug Reaction With Eosinophilia and Systemic Symptoms (DRESS): Redefining Beta-Lactam-Associated DRESS.

To the editor—Drug reaction with eosinophilia and systemic symptoms (DRESS) is a severe cutaneous adverse reaction (SCAR) that can occur with medication exposure, including antibiotics [1]. DRESS is characterized by diffuse rash, eosinophilia, and organ dysfunction. However, clinical presentation can be heterogenous [2], making standardized diagnostic criteria proposed by the RegiSCAR group critical to identification of DRESS [3]. Presentation is typically delayed with traditional teaching, suggesting symptom onset occurs 2–6 weeks following medication exposure [4]. Recent studies suggest a potentially shorter drug latency with antibiotic-associated DRESS [5]. However, the latency of confirmed beta-lactam DRESS in direct comparison with other antibiotic groups remains unknown. Using 2 previously published prospective multicenter cohorts of antibiotic hypersensitivity–tested patients from Melbourne, Australia, we identified patients with antibiotic-associated DRESS between April 2015 and June 2022 and compared patients with beta-lactam DRESS and vancomycin DRESS [6–8]. Adult (aged ≥18 years) patients who reported beta-lactam or vancomycin-associated DRESS, had a RegiSCAR score [3] of >2 (possible, probable, or definite DRESS), and had positive testing to the implicated antibiotic via a previously published ex vivo T-cell assay (enzyme-linked immunosorbent spot) or skin testing (ST; intradermal or patch test using previously deployed nonirritant concentrations of antibiotic) [7] were included. Patients with vancomycin DRESS also underwent human leukocyte antigen (HLA) typing for HLA-A*32:01, a known pharmacogenomic association [9]. DRESS patients positive to both vancomycin and a beta-lactam on any testing were excluded. Drug latency was defined as time from drug commencement until onset of DRESS. One sample Wilcoxon signed rank test was used to compare latency of beta-lactam DRESS with reported latency of 14 days, while linear regression was used for comparison with vancomycin latency.

TOO HOT TO GET DRESSED?

TOO HOT TO GET DRESSED?

S3281 A Rare Case of Drug-Induced Liver Injury (DILI) Due to Valproate Hepatocellular Injury

Introduction: Valproate is a widely-used antiepileptic drug which works by increasing gamma-aminobutyric acid (GABA) levels in the brain. We present a unique form of drug-induced liver injury (DILI) in a patient prescribed valproate for trigeminal neuralgia pain. Case Description/Methods: A 45-year old African American female with a history of hypertension and trigeminal neuralgia was prescribed divalproex for trigeminal neuralgia pain after trials of duloxetine, gabapentin, baclofen, oxcarbazepine, carbamazepine, topiramate, amitriptyline, and tizanidine failed to provide relief. Six weeks later she presented with a two week history of worsening nausea, diarrhea, fever, facial rash, production of dark phlegm, and grade 1 encephalopathy. Lab results showed acute liver failure (ALF) with total bilirubin 15.6 mg/dL, ALP 180 U/L, AST 937 U/L, ALT 943 U/L, and INR 2.8. Exam findings included scleral icterus, hepatomegaly, small volume ascites, and some small liver cysts. A diagnosis of DILI was made, with likely drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome. Divalproex was discontinued and the patient was admitted for two weeks of stabilizing treatment including N-acetylcysteine, lactulose, rifaximin, Vitamin K, and L-carnitine transfusion (Figure 1). The patient was evaluated for liver transplant, but it was ultimately not indicated given her subsequent improvement in liver function. An acute kidney injury developed but was resolved before patient discharge. Two weeks later the patient presented with signs of acute kidney injury. Upon readmission, complications including hepatic encephalopathy, macrocytic anemia, spontaneous bacterial peritonitis, and acute respiratory failure developed over the course of several weeks. All stabilizing treatment efforts were made but the patient ultimately developed septic shock and died. Discussion: DILI is the most common cause of ALF in the United States. Valproate-induced hepatotoxicity as a result of mitochondrial injury from impaired beta-oxidation and decreased tissue carnitine levels is one rare effect of use. Such hepatocellular injury typically shows very elevated AST and ALT levels with a smaller elevation in ALP. Early diagnosis of DILI is crucial to promptly discontinue use of the causative agent and begin optimal treatment. In the case of valproate, it is recommended that patients receive intravenous (IV) carnitine until symptoms improve. Liver transplant evaluation is crucial for ALF patients given the high morality risk.Figure 1.: 1A. Patient’s AST and ALT values over the course of her hospital admission. Figure 1B. Patient’s INR values over the course of her hospital admission.

In-hospital mortality in a dermatology department

Background: Far from popular belief making dermatological conditions benign and harmless, we know that some dermatoses may be life-threatening. The aim of our study was to evaluate the overall mortality resulting from dermatological disorders in our department because of the rarity of similar studies. Materials and Methods: We conducted a retrospective, observational study on all patients who died in the Ibn Sina Hospital of Rabat between January 2017 and December 2021 (a period of five years), after they were initially admitted to the dermatology department. Results: Among 1731 patients hospitalized during this period, 45 died, corresponding to an average of 2.6%. The male-to-female ratio was 1.9 and the mean age at death was 63.2 years. The mean number of comorbidities per patient was 1.2, dominated by diabetes. The reasons for hospitalization were as follows: twenty-three cases of extensive bullous dermatoses (60.5% of the cases), four cases of severe toxidermia (10.5%), three cases of erythroderma (7.8%), one case of acro-lentiginous melanoma, one case of squamous cell carcinoma, and one case of pyoderma gangrenosum. In twenty patients (52.6%), the cause of death was directly related to the dermatosis. In sixteen, the cause of death was septic shock of cutaneous origin. Sixteen patients (42.1%) died of causes unrelated to dermatosis. Conclusion: This study showed that life-threatening dermatoses are not uncommon. Among these conditions, autoimmune bullous dermatoses and severe toxidermia, such as TEN and DRESS syndrome, were found to be the most lethal. An advanced age, a surface area of skin involvement, mucosal involvement, associated comorbidities, and the development of sepsis may be considered poor prognostic factors.

S2968 DRESS Syndrome and Drug-Induced Liver Injury: A Product of Antibiotic Cocktail

S2968 DRESS Syndrome and Drug-Induced Liver Injury: A Product of Antibiotic Cocktail

CYCLIC FEVERS AND PLEURAL EFFUSIONS IN SUSPECTED PULMONARY HISTOPLASMOSIS

CYCLIC FEVERS AND PLEURAL EFFUSIONS IN SUSPECTED PULMONARY HISTOPLASMOSIS