MILITARY MEDICINE, 178, 12:e1384, 2013
Salmonella Septic Arthritis in a Patient Receiving Etanercept: Case Report and Review of the Literature Karen Sky, MD*; Col Ramon A. Arroyo, MC USAF (Ret.)†; Maj Angelique N. Collamer, MC USAF‡
CASE PRESENTATION A 69-year-old female with a 2-year history of rheumatoid arthritis treated for 1.5 years with etanercept and hydroxychloroquine presented to the emergency department with 24 hours of right groin pain. She was febrile to 102.4 F (39.1 C) and was unable to ambulate due to pain. Past medical history included fibromyalgia, spinal stenosis, hypertension, and a remote history of a cholecystectomy and partial colectomy for diverticulitis. Other outpatient medications were meloxicam, cyclobenzaprine, donnatal, fexofenadine, hydrochlorothiazide, metoprolol, esomeprazole, *Department of Rheumatology, Alaska VA Healthcare System, 1201 North Muldoon Road, Anchorage, AK 99504. †San Antonio Military Medical Center, 3851 Roger Brooke Drive, Fort Sam Houston, TX 78234. ‡Department of Internal Medicine, 633rd Medical Group Hospital, Joint Base Langley-Eustis, 77 Nealy Avenue, Building 255, Langley AFB, VA 23665. This case was presented as a 10-minute oral presentation at the Army/ Air Force ACP chapter meeting in 2009 during the rheumatology subspecialty session. The opinions and assertions contained within this manuscript are those of the authors and do not necessarily reflect official policy of the Veterans Administration, U.S. Army, U.S. Air Force, or the Department of Defense. doi: 10.7205/MILMED-D-13-00284
e1384
and aspirin. The patient was in her usual state of health before admission and had no history of malignancy or recent surgeries. She was a homemaker and had no history of tobacco, alcohol, or intravenous drug use. Review of systems was significant for 3 days of non-bloody loose stool. There was no history of diabetes, recent antibiotic use, or hemoglobinopathies. She had traveled to Mexico on a cruise 6 months earlier; however, she denied buying food from street vendors or eating unpasteurized foods. On examination she exhibited no pain at rest or with axial loading. The iliopsoas sign was negative and hip flexor strength was normal, however, severe pain was elicited with hip movement at 80 flexion, 45 abduction, and 10 internal rotation in both the left and right hips. Tenderness to palpation was present over the pubic symphysis. Laboratory data revealed an erythrocyte sedimentation rate of 101 mm/h and C-reactive protein of 22.4 mg/dL (224 mg/L). White blood cell count was 4.3 10(3)/mm3, hemoglobin and hematocrit were 9.4 g/dL (5.8 mmol/L) and 27.8% (0.278), respectively, and platelets were normal. Liver function tests, creatinine kinase, renal function, and thyroid stimulating hormone were unremarkable. Blood and urine cultures were negative. An anterior/posterior conventional radiograph of the pelvis was unremarkable without evidence of avascular necrosis or other bony pathology. Pelvic ultrasound revealed no pelvic pathology. Computed tomography (CT) of the abdomen and pelvis was also unrevealing. Magnetic resonance imaging (MRI) of the lumbar spine did not show an epidural abscess or other abnormality. An MRI of the pelvis revealed a small amount of fluid in the pubic symphysis and adjacent bony enhancement in the right superior pubic ramus (Fig. 1). Blood cultures, joint aspiration and bone biopsy of the pubic symphysis were performed. Twenty-four hours later Gram-negative rods were isolated from the blood cultures and 3 days later the culture grew Salmonella Group D. Initial Gram stain of joint aspirate was negative, but after 4 days Gram-negative rods were isolated and 7 days later cultures grew Salmonella Group D. Fluid cytology of the aspirate was without malignant
+
INTRODUCTION Antitumor necrosis factor alpha (anti-TNFa) agents are known to increase the risk for severe and atypical infections, including septic arthritis. Numerous atypical organisms causing granulomatous infections have been reported, most commonly Mycobacterium tuberculosis, Histoplasma, atypical mycobacteria, Candida, Aspergillus, Listeria, Cryptococcus, and Coccidioides.1 Salmonella joint sepsis occurring in antiTNF-treated patients has rarely been described, and has never been reported as a single organism in the pubic symphysis. Herein we report the first case of pubic symphysis Salmonella septic arthritis, review the literature and discuss the likely mechanisms of action leading to an anti-TNF associated Salmonella joint sepsis.
MILITARY MEDICINE, Vol. 178, December 2013
Downloaded from https://academic.oup.com/milmed/article-abstract/178/12/e1384/4267478 by guest on 24 September 2018
ABSTRACT Antitumor necrosis factor alpha agents are known to increase the risk for severe and atypical infections. Numerous atypical organisms have been reported previously, however, there is a paucity of reports of Salmonella as a complication of these therapies. We report a case of a 69-year-old female who developed Salmonella septic arthritis of the pubic symphysis while taking etanercept that resolved with cessation of etanercept and antibiotic treatment and we review the literature regarding this complication. Awareness of susceptibility to Gram-negative intracellular organisms and reactivation of dormant infections due to the mechanism of action of antitumor necrosis factor alpha medications is vital.
Case Report
FIGURE 1. MRI of the pelvis post-gadolinium contrast showing abnormal fluid in the pubic symphysis and adjacent right sided bony enhancement (arrows).
cells and the bone biopsy was Gram stain negative and grew no organisms. METHODS Literature search for reports of Salmonella septic arthritis of the pubic symphysis was performed using PubMed MeSH terms “Salmonella” and “pubic symphysis,” which resulted in no matches. “Salmonella” and “infliximab” resulted in 15 articles, revealing 3 cases of Salmonella infection of a joint, none of which were in the pubic symphysis. “Salmonella” and “adalimumab” resulted in 2 articles, one of relevance. “Salmonella” and “etanercept” resulted in 6 matches, 1 case of Salmonella infection of a joint. A Google Scholar search was performed using the terms “Salmonella” and “pubic symphysis”, and “Salmonella” and “anti-TNF,” which resulted in 4 relevant articles. The references from the obtained articles were reviewed for other relevant literature. LITERATURE REVIEW Anti-TNFa medications are commonly used to treat systemic inflammatory joint diseases and the increased risk of tuberculosis and atypical infections with their use is now widely accepted.2 Seven other cases of septic arthritis attributed to Salmonella infections in patients receiving anti-TNF medications have been described in the literature (Table I).3–8 MILITARY MEDICINE, Vol. 178, December 2013
DISCUSSION Septic arthritis is a clinical emergency and most often occurs as a result of occult bacteremia. The synovium is particularly vulnerable because it is highly vascular and lacks a protective basement membrane.11 Major risk factors for septic arthritis include preexisting damage in the affected joint, immunosuppression, non-intact skin and intravenous drug abuse.11 Gram staining identifies only 40 to 50% of cases of Gram-negative septic arthritis, making the diagnosis challenging.11 Salmonella is a Gram-negative intracellular organism that can present in 5 major forms: gastroenteritis, enteric fever, bacteremia, focal disease, and a carrier state.12 The carrier state is of particular importance as 0.2 to 0.6% of patients previously infected with nontyphoidal Salmonella can be chronic asymptomatic carriers.12 Only half of patients who have septic arthritis due to Salmonella recall a history of a diarrheal illness.5 However, the bacteria can lie dormant in the reticuloendothelial system, only reactivating when the host is immunosuppressed.13 Salmonella is a rare cause of bone and joint infection, accounting for
Salmonella Septic Arthritis in a Patient Receiving Etanercept: Case Report and Review of the Literature Karen Sky, MD*; Col Ramon A. Arroyo, MC USAF (Ret.)†; Maj Angelique N. Collamer, MC USAF‡
CASE PRESENTATION A 69-year-old female with a 2-year history of rheumatoid arthritis treated for 1.5 years with etanercept and hydroxychloroquine presented to the emergency department with 24 hours of right groin pain. She was febrile to 102.4 F (39.1 C) and was unable to ambulate due to pain. Past medical history included fibromyalgia, spinal stenosis, hypertension, and a remote history of a cholecystectomy and partial colectomy for diverticulitis. Other outpatient medications were meloxicam, cyclobenzaprine, donnatal, fexofenadine, hydrochlorothiazide, metoprolol, esomeprazole, *Department of Rheumatology, Alaska VA Healthcare System, 1201 North Muldoon Road, Anchorage, AK 99504. †San Antonio Military Medical Center, 3851 Roger Brooke Drive, Fort Sam Houston, TX 78234. ‡Department of Internal Medicine, 633rd Medical Group Hospital, Joint Base Langley-Eustis, 77 Nealy Avenue, Building 255, Langley AFB, VA 23665. This case was presented as a 10-minute oral presentation at the Army/ Air Force ACP chapter meeting in 2009 during the rheumatology subspecialty session. The opinions and assertions contained within this manuscript are those of the authors and do not necessarily reflect official policy of the Veterans Administration, U.S. Army, U.S. Air Force, or the Department of Defense. doi: 10.7205/MILMED-D-13-00284
e1384
and aspirin. The patient was in her usual state of health before admission and had no history of malignancy or recent surgeries. She was a homemaker and had no history of tobacco, alcohol, or intravenous drug use. Review of systems was significant for 3 days of non-bloody loose stool. There was no history of diabetes, recent antibiotic use, or hemoglobinopathies. She had traveled to Mexico on a cruise 6 months earlier; however, she denied buying food from street vendors or eating unpasteurized foods. On examination she exhibited no pain at rest or with axial loading. The iliopsoas sign was negative and hip flexor strength was normal, however, severe pain was elicited with hip movement at 80 flexion, 45 abduction, and 10 internal rotation in both the left and right hips. Tenderness to palpation was present over the pubic symphysis. Laboratory data revealed an erythrocyte sedimentation rate of 101 mm/h and C-reactive protein of 22.4 mg/dL (224 mg/L). White blood cell count was 4.3 10(3)/mm3, hemoglobin and hematocrit were 9.4 g/dL (5.8 mmol/L) and 27.8% (0.278), respectively, and platelets were normal. Liver function tests, creatinine kinase, renal function, and thyroid stimulating hormone were unremarkable. Blood and urine cultures were negative. An anterior/posterior conventional radiograph of the pelvis was unremarkable without evidence of avascular necrosis or other bony pathology. Pelvic ultrasound revealed no pelvic pathology. Computed tomography (CT) of the abdomen and pelvis was also unrevealing. Magnetic resonance imaging (MRI) of the lumbar spine did not show an epidural abscess or other abnormality. An MRI of the pelvis revealed a small amount of fluid in the pubic symphysis and adjacent bony enhancement in the right superior pubic ramus (Fig. 1). Blood cultures, joint aspiration and bone biopsy of the pubic symphysis were performed. Twenty-four hours later Gram-negative rods were isolated from the blood cultures and 3 days later the culture grew Salmonella Group D. Initial Gram stain of joint aspirate was negative, but after 4 days Gram-negative rods were isolated and 7 days later cultures grew Salmonella Group D. Fluid cytology of the aspirate was without malignant
+
INTRODUCTION Antitumor necrosis factor alpha (anti-TNFa) agents are known to increase the risk for severe and atypical infections, including septic arthritis. Numerous atypical organisms causing granulomatous infections have been reported, most commonly Mycobacterium tuberculosis, Histoplasma, atypical mycobacteria, Candida, Aspergillus, Listeria, Cryptococcus, and Coccidioides.1 Salmonella joint sepsis occurring in antiTNF-treated patients has rarely been described, and has never been reported as a single organism in the pubic symphysis. Herein we report the first case of pubic symphysis Salmonella septic arthritis, review the literature and discuss the likely mechanisms of action leading to an anti-TNF associated Salmonella joint sepsis.
MILITARY MEDICINE, Vol. 178, December 2013
Downloaded from https://academic.oup.com/milmed/article-abstract/178/12/e1384/4267478 by guest on 24 September 2018
ABSTRACT Antitumor necrosis factor alpha agents are known to increase the risk for severe and atypical infections. Numerous atypical organisms have been reported previously, however, there is a paucity of reports of Salmonella as a complication of these therapies. We report a case of a 69-year-old female who developed Salmonella septic arthritis of the pubic symphysis while taking etanercept that resolved with cessation of etanercept and antibiotic treatment and we review the literature regarding this complication. Awareness of susceptibility to Gram-negative intracellular organisms and reactivation of dormant infections due to the mechanism of action of antitumor necrosis factor alpha medications is vital.
Case Report
FIGURE 1. MRI of the pelvis post-gadolinium contrast showing abnormal fluid in the pubic symphysis and adjacent right sided bony enhancement (arrows).
cells and the bone biopsy was Gram stain negative and grew no organisms. METHODS Literature search for reports of Salmonella septic arthritis of the pubic symphysis was performed using PubMed MeSH terms “Salmonella” and “pubic symphysis,” which resulted in no matches. “Salmonella” and “infliximab” resulted in 15 articles, revealing 3 cases of Salmonella infection of a joint, none of which were in the pubic symphysis. “Salmonella” and “adalimumab” resulted in 2 articles, one of relevance. “Salmonella” and “etanercept” resulted in 6 matches, 1 case of Salmonella infection of a joint. A Google Scholar search was performed using the terms “Salmonella” and “pubic symphysis”, and “Salmonella” and “anti-TNF,” which resulted in 4 relevant articles. The references from the obtained articles were reviewed for other relevant literature. LITERATURE REVIEW Anti-TNFa medications are commonly used to treat systemic inflammatory joint diseases and the increased risk of tuberculosis and atypical infections with their use is now widely accepted.2 Seven other cases of septic arthritis attributed to Salmonella infections in patients receiving anti-TNF medications have been described in the literature (Table I).3–8 MILITARY MEDICINE, Vol. 178, December 2013
DISCUSSION Septic arthritis is a clinical emergency and most often occurs as a result of occult bacteremia. The synovium is particularly vulnerable because it is highly vascular and lacks a protective basement membrane.11 Major risk factors for septic arthritis include preexisting damage in the affected joint, immunosuppression, non-intact skin and intravenous drug abuse.11 Gram staining identifies only 40 to 50% of cases of Gram-negative septic arthritis, making the diagnosis challenging.11 Salmonella is a Gram-negative intracellular organism that can present in 5 major forms: gastroenteritis, enteric fever, bacteremia, focal disease, and a carrier state.12 The carrier state is of particular importance as 0.2 to 0.6% of patients previously infected with nontyphoidal Salmonella can be chronic asymptomatic carriers.12 Only half of patients who have septic arthritis due to Salmonella recall a history of a diarrheal illness.5 However, the bacteria can lie dormant in the reticuloendothelial system, only reactivating when the host is immunosuppressed.13 Salmonella is a rare cause of bone and joint infection, accounting for
