Safely subtracting sulfa allergy: It's time.

To investigate whether a self-reported history of allergy to sulfa-based drugs is a predictor for subsequent adverse reactions to topical carbonic anhydrase inhibitors (CAIs). A retrospective case-controlled cohort study via chart review was performed on 1,287 patients with a diagnosis of glaucoma. The outcome measure was the development of an adverse reaction (either ocular, systemic, or both) within at least 30 days after receipt of 1 of 4 classes of topical glaucoma medications: CAIs (dorzolamide and brinzolamide), prostaglandin analogues, beta-adrenergic blockers, and alpha2-adrenergic agonists. Patients with a self-reported history of sulfa allergy had significantly more ocular adverse reactions after the initiation of any of the topical antiglaucoma medications when compared to those patients with no reported allergies. Patients with a self-reported sulfa allergy and patients who self-reported other, nonsulfa-related allergies had similar rates of adverse reactions to most of the topical medications. The patients reporting a sulfa allergy who used topical CAIs did not have more adverse reactions compared with patients who reported having other, nonsulfa-related allergies who used topical CAIs. Self-reported sulfa-allergic patients had similar rates of adverse reactions to topical CAIs compared with topical prostaglandin analogues. It may be safe to use a topical CAI in patients who report a history of a sulfa allergy. Patients with medication allergies of any kind may be more likely to develop allergic reactions to other, unrelated drug classes.

IMMUNE RECONSTITUTION INFLAMMATORY SYNDROME AFTER USE OF ANTI-RETROVIRAL THERAPY IN COVID-19

The introduction of imatinib has substantially changed the approaches to the therapy of chronic myeloid leukemia. However, this drug can cause hepatic failure and death in rare cases. This report describes a clinical case of acute, toxic imatinib-induced hepatitis in a 56-year-old woman with chronic myeloid leukemia and concomitant sulfa allergy and rheumatoid arthritis. The patient developed acute imatinib-induced hepatitis after three months of treatment with imatinib and three days after increasing the imatinib dosage from 400 mg per day to 600 mg per day, resolving within three months after imatinib discontinuation and prednisolone administration. This confirms the necessity of great caution during imatinib therapy and the monitoring of liver tests. Approximately 25 reports about clinical cases of imatinib-induced hepatitis have been published up to the present.

The Efficacy and Safety of Amoxicillin, Trimethoprim-Sulfamethoxazole, and Spironolactone for Treatment-Resistant Acne Vulgaris

Much attention has been given to the development of osteonecrosis of the jaws, concomitant with a history of bisphosphonate usage, particularly regarding inciting dental procedures. This report describes a case of bisphosphonate-related osteonecrosis of the hard palate after the harvesting of a subepithelial connective tissue (CT) graft for treatment of gingival recession (GR) in the mandible. A 60-year-old female sought periodontal therapy for GR. Her medical history revealed the use of alendronate for osteopenia, hypothyroidism, sulfa allergy, and >18 regimens of steroid formulations (oral, inhaled, and topical) for various upper respiratory and dermatologic disorders. The hard palate was selected as the donor site for the subepithelial CT graft. At a 4-month postoperative evaluation, osteonecrosis was evident in the palatal site. Successful clinical outcome was achieved after conservative debridement, antibiotics, and use of chlorhexidine gluconate. It is advised that a patient's medical history include current and past intake of bisphosphonates and comorbidities that could predispose to the development of osteonecrosis of the jaws. Attempts should be instituted to achieve primary wound closure of the donor site in patients who have taken bisphosphonates. Postoperative follow-up of the donor site of CT grafts should continue for at least 6 months for surveillance of bisphosphonate-related osteonecrosis.

To describe the clinical characteristics of patients referred for gold therapy and determine the reason for referral. We conducted a chart review of patients referred for gold at the Mary Pack Arthritis Program, Vancouver, Canada, from July 2007 to July 2009. The sample included 69 female and 12 male patients. Diagnosis was rheumatoid arthritis (RA) in 71/81, psoriatic arthritis in 5, juvenile idiopathic arthritis (JIA) in 2, Sjögren syndrome in 1, undifferentiated polyarthritis in 1, and spondyloarthritis in 1. Twenty of 81 patients had received gold before: 15 were referred for a second course, 4 a third course, and 1 a fourth course. Ten of 81 patients were referred for gold as their first disease-modifying antirheumatic drug (DMARD). Seventy-one had received prior DMARD: 1 prior DMARD in 22 patients, 2 in 24 patients, 3 in 15 patients, and > 3 in 6 patients. Four patients had received prior biologic therapy plus 2 to 4 prior DMARD. Twelve of 71 received gold monotherapy, 56/71 received gold/DMARD combinations, and 3 received gold/biologic/DMARD combinations. Reasons for referral included failure of other DMARD in 54 patients, limited DMARD options in 50 (chronic liver disease in 34, sulfa allergy in 7, high alcohol consumption in 5, and planning pregnancy in 4), physician choice in 12, previous benefit from gold in 10, benefit of clinic support in 10, inappropriate for biologics in 7, patient choice in 4, and failure of biologics in 3. The most common reasons for referral to gold clinic in 2007 to 2009 are failure of other DMARD and limited DMARD options due to underlying liver disease.

e19026 Background: COX-2 is often overexpressed in NSCLC leading to high systemic PGE2 levels that in turn play a role in NSCLC pathogenesis. Changes in urine PGE-M (the major PGE2 metabolite) reflect changes in systemic & intratumoral PGE2 [Csiki et al. Clin Cancer Res 11:6634, 2005]. A ≥70% decline in PGE-M in NSCLC patients (pts) treated with celecoxib (C) (400 mg bid) + docetaxel (D) was associated with an apparent survival benefit [Ibid]. To effect maximum COX-2 inhibition we tested a higher C dose in a subsequent phase II trial. Methods: Eligibility: previously treated NSCLC, PS 0–2, evaluable/measurable disease, adequate marrow, renal & hepatic function, no current NSAID or sulfa allergy. Urine PGE-M measured prior to & 5–10 days after C 600 mg PO bid. Pts with ≥70% decline in PGE-M continued on C + D 75 mg/m2 or pemetrexed 500 mg/m2 q3wk x 4 cycles followed by maintenance C 400 mg PO bid until PD or drug intolerance. Results: 21 pts enrolled; F=7, M=14; 2 ineligible (1 carcinoid; 1 elevated LFT); 2 stopped C early (1 ARF; 1 pruritus). Mean PGE-M levels decreased from 38.9 to 7.8 ng/mg Cr pre- & post-C (mean change = 80%; P=0.002). The mean decline was greater in current & former smokers (81%; P=0.002) compared to never smokers (46%; P=0.19). Males had higher pre- treatment PGE-M (44 vs. 28.8 ng/mg Cr; P=0.21). Males had a significant decrease in mean PGE-M levels after C (78%; P=0.011); a similar albeit not significant change occurred in females (P=0.12). 12 screened pts (57%) had a ≥70% decline in PGE-M & received treatment with C + chemotherapy; 8 pts are evaluable for response; SD = 6; PD = 2. Treatment was well tolerated with no cardiac toxicities noted. Conclusions: These preliminary data indicate C 600 mg bid effectively inhibits intratumoral COX-2 in >50% NSCLC pts, a higher percentage than our previous trial using C 400 mg bid. The effect is greatest in former & current smokers & males compared to never smokers & females. Toxicities are acceptable. Accrual is ongoing. [Funding: VICC Lung Cancer SPORE CA90949]. No significant financial relationships to disclose.

Efficacy of Nitazoxanide for Cyclosporiasis in Patients with Sulfa Allergy

Drug Allergies in Immunodeficiencies: a Single-Center Experience in Southern California

A 41-year-old woman with hidradenitis suppurativa on adalimumab was admitted with Pneumocystis jirovecii pneumonia (PJP). Concomitant medications included prednisone 20 mg daily, initiated several weeks prior for a new diagnosis of sarcoidosis, based on cervical adenopathy biopsy showing non-necrotizing granulomata and pulmonary and hepatitis nodules on imaging. The patient subsequently developed fevers, chills, shortness of breath, and malaise. Repeat chest imaging showed nodularity and bilateral ground glass opacities. Bronchoscopy confirmed PJP pneumonia. Because of a reported sulfa allergy, she began atovaquone instead of trimethoprim-sulfamethoxazole (TMP-SMX) but developed a fever and a new truncal rash after 10 days. Inpatient admission was prompted by tachycardia and elevated alanine aminotransferase to 191 U/l, aspartate aminotransferase to 79 U/l, and thrombocytopenia with platelets at 51 K/μl. On examination, a pink confluent morbilliform rash covered much of the trunk, bilateral arms, palms, and thighs, with macular purpura on the upper abdomen and inframammary skin (Figure 1). Punch biopsy from the left upper abdomen demonstrated a mild interface dermatitis with vacuolar change of basal layer keratinocytes and a brisk perivascular lymphocytic infiltrate involving the superficial dermis (Figure 2). This constellation of findings was suspicious for drug reaction and eosinophilia with systemic symptoms (DRESS), potentially from atovaquone. Atypical features arguing against DRESS included short duration between drug initiation and rash onset, lack of peripheral eosinophilia or atypical lymphocytes, and clinical worsening despite steroid treatment. Persistent fevers, cytopenias, and worsening respiratory status prompted a transfer to the intensive care unit. Further work-up revealed a positive result for urine Histoplasma antigen, which remained elevated over 10 of 11 tests. Fungal immunodiffusion testing also supported the diagnosis of disseminated histoplasmosis, and intravenous amphotericin treatment was initiated. Despite steroid treatment, the patient had worsening cytopenias, which raised concerns for hemophagocytic lymphohistiocytosis (HLH). This diagnosis was confirmed via six out of nine diagnostic criteria, including significantly elevated ferritin levels (>40,000 ng/ml), recurrent fevers, pancytopenia, bone marrow biopsy indicating hemophagocytosis, and high levels of chemokine ligand 9 (CXCL9) at 16,550, as well as soluble IL-2R at 5,479.1 The patient improved clinically after receiving amphotericin B, dexamethasone, and TMP-SMX. HLH is a severe immune dysregulation characterized by hyperactivated hemophagocytic macrophages.1 Reactive hemophagocytic lymphohistiocytosis (RHLH) is linked to underlying infection, malignancy, and rheumatological diseases.1 Cutaneous manifestations are present in 10–20% of cases of RHLH and most commonly present as a transient maculopapular rash.2, 3 DRESS is a type IV drug hypersensitivity reaction distinguished by its delayed onset, association with human herpesviruses (HHV) 6 and 7, and prolonged clinical symptoms after drug discontinuation.1, 4 There is significant overlap between HLH and DRESS, as both exhibit rash, fever, and multi-organ damage. In a review by Yang et al. of 23 cases with a codiagnosis of HLH and DRESS, an increasing number of reports involved drug-induced HLH and biopsy-proven hemophagocytosis in DRESS, suggesting that these two diseases lie on the same spectrum.2 A key difference is in the pathophysiology, with DRESS showing CD4 T cell elevation and HLH exhibiting macrophage activation.1 This patient presented with a diffuse maculopapular rash and systemic symptoms after starting a new drug, which raised initial concerns for DRESS. HLH work-up was prompted after continued deterioration despite steroid treatment. We suspect that dual immunosuppression with adalimumab and prednisone explains the development of her disseminated histoplasmosis. Despite the absence of a personal or family history of immunodeficiency, further evaluation by immunology was advised, as immunodeficiencies like common variable immunodeficiency (CVID) can also cause granulomatous disease and sarcoidosis. We highlight this unique case to discuss the overlapping features between HLH and DRESS and the distinctions that led to a diagnosis of RHLH in the setting of disseminated histoplasmosis.

Heterotopic ossification (HO) has historically been a common radiographic finding after total hip arthroplasty (THA), with an incidence 10–40%. It is a potentially serious complication, with patients reporting pain and restricted motion. Perioperative protocols have changed over the years and now universally include tranexamic acid (TXA) and non-steroidal anti-inflammatories (NSAIDs). There is evidence that TXA and NSAIDs can help inhibit the development of HO. The primary objective of this study was to determine what the true incidence of HO is in modern THA and whether routine perioperative medications influence this. We secondarily aimed to understand whether there was a difference in HO formation between surgical approaches to the hip (direct anterior, posterior, direct lateral). A retrospective cohort was developed consisting of 315 consecutive patients undergoing total hip arthroplasty during the period of April 2023-June 2024 at a single academic centre. This cohort was then divided by surgical approach with 105 allocated to each group (direct anterior, posterior, lateral). Patients were included if they had an elective primary THA and had radiographs taken at 6 month or 1 year follow-up. A standard perioperative protocol is established at this institution with patients receiving between 1g–1.5g of preoperative and postoperative oral TXA. Patients also receive 14 days of celecoxib if no contraindications to this exist. Radiographs were independently assessed by 2 authors for the presence of HO and were graded according to the Brooker classification. Patient demographics, comorbidities and perioperative medications were collected. Regression was then performed to identify predictors of HO formation. 315 patients (105 direct anterior, 105 direct lateral, 105 posterior) underwent THA during the period of data collection. 5.5% (17/315) developed HO on a postoperative radiograph at 6 months or 1 year follow-up. Only 1.6% (5/315) of patients developed more than Brooker grade 1 HO, with all of these occurring in the direct lateral group. No patients with HO required any further intervention. Patients were significantly more likely to develop HO if they had a direct lateral approach to the hip or did not receive postoperative celecoxib due to a reported sulfa allergy or chronic kidney disease. Patients undergoing THA are unlikely to develop clinically meaningful HO with modern perioperative protocols. The use of celecoxib combined with a more muscle sparing surgical approach appeared to be associated with less development of HO in this series.

BackgroundDespite available prophylaxis, Pneumocystis jirovecii pneumonia (PJP) still occurs in immunocompromised hosts. We set out to determine the overall burden of PJP among cancer patients in the modern era at our cancer center. Furthermore, we sought to describe reasons for failure to use prophylaxis among these patients.MethodsIn this retrospective cohort study, we identified PJP cases among patients admitted between January 2007 and December 2016 at our center. PJP was defined as any positive test (immunofluorescence or PCR) from sputum and/or bronchoalveolar lavage. Patient demographics, underlying malignancy, anti-pneumocystis antibiotics and mortality were assessed through electronic medical records. Current National Comprehensive Cancer Network (NCCN) guidelines were used to determine who should have received prophylaxis. Cases not on prophylaxis at the time of diagnosis were reviewed to determine reasons why prophylaxis was not administered. Incidence of PJP for the last 5 years of the study was estimated based on a Poisson distribution.ResultsA total of 37 patients had confirmed PJP over the 10-year study period. The majority were male (68%) with a median age of 60 years (IQR: 47, 67). The most common underlying malignancy was acute myeloid leukemia (24%); 24/37 (65%) were bone marrow transplant recipients. The 5-year incidence between 2012 and 2016 was 2.28 per 10,000 inpatient days (95% CI, 1.50–3.32). There was no evidence of clustering of PJP diagnoses. Overall, 26/37 (70%) of PJP patients were not on prophylaxis at the time of diagnosis, 12 of whom met NCCN criteria for use. Twenty-three were deceased by the end of the study with 11/23 (48%) deaths occurring within 30 days of diagnosis. The main reason prophylaxis was not administered was neutropenia (19%). A documented sulfa allergy was noted in seven PJP cases (19%); 2/7 (29%) were not administered alternate prophylaxis despite recommendations for use.ConclusionPJP incidence in this large cohort of cancer patients was low, but one-third of patients who developed PJP were not on recommended prophylaxis in accordance with NCCN guidelines. Infection Prevention and Antimicrobial Stewardship teams should enhance efforts to address missed opportunities for PJP prophylaxis in high-risk patients.DisclosuresS. Pergam, Merck: Consultant, Consulting fee. Chimerix: Consultant, Consulting fee.

BackgroundDespite antiretroviral therapy (ART), some patients do not achieve IR. Moreover, GI bacterial translocation may lead to a decrease in CD4 counts with an increase in IL-6 in blood. However, the effect of OI prophylaxis on the GIM, bacterial translocation and IR has not been studied in HIV+ veterans. Here we studied the gut microbiome and bacterial translocation in VA patients with (i) stable HIV on ART (controls), (ii) newly diagnosed HIV starting on ART (new dx) and OI prophylaxis, and (iii) resuming ART (resumers).MethodsBlood and stool specimens from 16 controls, 4 new dx and 3 resumers were obtained at 3 visits, as well as clinical and virological data. PCR electrospray ionization mass spectrometry (ESI-MS) was performed on blood samples to detect bacteria. Quantitative cultures and gut microbiome (deep sequencing bacterial 16S rRNA) was done on stool.ResultsThere was no relation between CD4 count, log CFU TMP-SMX-resistant Gram-negative bacteria (GNRs) or total anaerobes. Except for 2 control patients with a decrease in CD4 count <200, none took TMP-SMX. One of these control patients started TMP-SMX, while the other took atovaquone. Neither had TMP-SMX R GNRs in stool, despite low CD4 /TMP-SMX. Major stool phyla in controls were Bacteroidetes (37 ± 19%), Firmicutes (37 ± 14%), Proteobacteria (15 ± 14%); while resumers had 54 ± 15% Bacteroidetes, 33 ± 12% Firmicutes and 7 ± 1% Proteobacteria. Only one new dx individual had CD4 count <200 at dx and took doxycycline initially for hidradenitis supparativa. Dapsone was initiated due to sulfa allergy. He was also diagnosed with lung cancer, treated with resection/XRT and received cefazolin. His VL became undetectable but CD4 <200. He had persistence of TMP-SMX-resistant GNRs despite dapsone and a shift in his GIM was observed over the first 6 months of care, i.e., Bacteroidetes decreased from 61.5% to 29.5% and Firmicutes increased from 30.6% to 53.3%.ConclusionOI prophylaxis does not affect the GIM of stable HIV VA patients on ART. TMP-SMX-resistant GNRs in stool are unrelated to TMP-SMX exposure or CD4 count. Other antibiotics such as doxycycline can alter GI microbiota and may affect immune reconstitution.Disclosures All authors: No reported disclosures.

5-aminosalicylates (5-ASA) remain an important strategy in the induction and maintenance of remission of inflammatory bowel diseases especially in ulcerative colitis. The prototypical drug of this class, sulfasalazine is generally well tolerated with severe hypersensitivity reactions and hepatotoxicity also described within the literature. When approaching a patient with an adverse reaction to 5-ASA, it can be difficult to differentiate clinically between a sulfa allergy versus a 5-ASA allergy versus a malignancy. We report on a case with initial signs and symptoms suggestive of a sulfa/5-ASA allergy that was subsequently found to be malignant in nature.

Introduction/Objective Post-transplant immunosuppression predisposes patients to severe complications from opportunistic infections, including Toxoplasma gondii. Typically asymptomatic and self-limited in immunocompetent individuals, Toxoplasma gondii can cause life-threatening disseminated disease in immunocompromised patients like solid organ transplant recipients. The challenge in diagnosing Toxoplasmosis is further exacerbated in patients receiving prophylactic therapy with agents such as Atovaquone, which may mask clinical suspicion. This case report describes a fatal presentation of disseminated Toxoplasmosis in a kidney transplant recipient. Methods/Case Report A 44-year-old male with a history of deceased donor kidney transplant presented to the emergency department two months post-transplant with symptoms of malaise, shortness of breath, hypoxemia, and hypotension. Despite medical interventions, the patient deteriorated rapidly, developing acute hypoxemic respiratory failure and septic shock requiring intubation. Subsequently, he succumbed to multisystem organ failure five days after admission. The autopsy revealed disseminated Toxoplasma gondii infection, with tachyzoites/bradyzoites identified in multiple organs, including the brain, bone marrow, and lymph nodes. Positive Toxoplasma immunohistochemical staining and PCR confirmed the diagnosis. Results (if a Case Study enter NA) NA Conclusion Toxoplasma infection in post-transplant patients can manifest as a severe and potentially fatal complication. Dissemination can arise from the reactivation of latent infection, donor transmission, or new acquisition. In this case, the infection likely resulted from the reactivation of latent infection in the donor, compounded by immunosuppression in the recipient. Notably, the patient received Atovaquone prophylaxis due to a sulfa allergy. Nonetheless, the case highlights the potential for delayed diagnosis due to atypical presentations in immunocompromised patients. Clinicians should maintain a high index of suspicion for Toxoplasma infection in post- transplant patients, particularly in those with unexplained clinical deterioration. This case emphasizes the importance of maintaining a high index of suspicion for T. gondii infection in post-transplant patients, even in those receiving prophylaxis.