Diffuse lymphadenitis due to Toxoplasmosis (primary infection in an otherwise immunocompetent patient).
Brief History of Present Illness
Patient is a 19 year old man with past medical history of childhood asthma who presented to our institution in December 2017 with a one week history of fevers and chills accompanied by extreme fatigue. This was in the context of a four month history of generally “not feeling well”. Since September 2017, he complained of recurrent episodes of upper respiratory tract infections. He sought care in urgent care clinics and his primary care physician’s office several times and had taken several courses of oral antibiotics including azithromycin, clindamycin and penicillin. On presentation, he also reported swollen “glands” involving his axilla, neck and groin. He also reported a fine rash involving his arms, trunk and legs (Figure 1).
Patient was transferred to our hospital from a smaller regional medical center. There, he was found to have one out of two sets of blood cultures positive for methicillin resistant Staphylococcus aureus (MRSA). The patient received IV Vancomycin at the outside hospital before his transfer to our institution.
Past Medical and Surgical History
Attention deficit hyperactivity disorder
Tonsillectomy at age 8
History of placement of myringotomy tubes at age 8
Clindamycin causes rash
Sulfa containing drugs cause hives
Single, enrolled in college, not sexually active, does not smoke or drink, no recent travel outside the state of South Carolina or any foreign travel, no pets. He is an avid red meat eater.
Hypertension in grandparents
Does not take any medications on regular basis
The patient appeared anxious. His temperature was 38.3 degrees C, respiratory rate was 21 breaths/min, oxygen saturation 95% on room air, heart rate was 129 beats/min and blood pressure 119/79 mm Hg. Head, eyes, ears and nose exam was within normal limits. He was noted to have extensive anterior and posterior cervical and axillary lymphadenopathy. His tongue was laterally deviated to the left side. Cardiac exam was noted for tachycardia. Pulmonary exam was noted for decreased breath sounds. Abdominal and musculoskeletal exam was within normal limits. He was noted to have an erythematous, blotted and non- blanchable rash all over his chest, back and arm (Figure 1).
Blood chemistry was within normal limits, however, he was noted to have a creatinine of 2.6 mg/dl. Liver enzymes were within normal limits with aspartate aminotransferase (AST) 25 IU/L (reference range 12-38 IU/L), alkaline phosphatase 89 IU/L (reference range 25-100 IU/L) and alanine aminotransferase 19 IU/L (reference range 10-45 IU/L). His white blood cell count was 23,000 cells/mm3 (reference range 4.8-10.3 K/mm3) with 71% neutrophils, 13% eosinophils, 7% lymphocytes and 1% monocytes. Platelets were 143,000/mm3. As part of his AKI work up, he was noted to have 20 eosinophils/HFP in his urine.
His HIV screen was negative. Hepatitis B surface antigen was negative. EBV serology was negative and Epstein Barr virus PCR in blood was negative. Six additional sets of blood cultures were negative. His CRP was 4.03 mg/dl and sedimentation rate was 56 mm/hr. Peripheral blood smear was noted for leukocytosis, eosinophilia, normocytic anemia and thrombocytopenia. Rapid strep throat test and monospot test were also negative.
In order to investigate extensive cervical lymphadenopathy, he had CT scans of soft tissue of his neck and chest (Figure 2 and 3). He was found to have numerous submandibular, cervical, intraparotid and supraclavicular lymph nodes bilaterally. He was also noted to have frothy mucoid material within the bilateral maxillary, ethmoid, sphenoid and frontal sinuses likely representing acute sinusitis. CT scan of chest without contrast was noted for extensive mediastinal, axillary and periportal lymphadenopathy with splenomegaly. There was an initial concern for a primary lymphoproliferative disorder. MRI brain did not reveal any infiltrative changes.
Clinical Course Prior to Diagnosis
The patient continued to have intermittent fevers while hospitalized and had an extensive work up to address his fevers and lymphadenopathy. He continued to have pruritus associated with the rash and was started on prednisone 80 mg per day following which his appetite and sleep improved. His rash slowly improved as well. He completed 14 days therapy with IV daptomycin for MRSA bloodstream infection. Transesophageal echocardiogram did not reveal any vegetations.The patient underwent a core needle biopsy of his right axillary lymph node which was inconclusive. This was followed by an excisional biopsy of his left inguinal lymph node, which was sent for pathology.
- Disseminated Tuberculosis
Diagnostic Procedure and Tests
Punch biopsy of his rash from his left thigh was noted for spongiotic and interface dermatitis, likely a drug rash. It did not show any evidence of vasculitis. Right axillary lymph node biopsy was noted for reactive lymphoid tissue in an inflamed background with occasional eosinophils. Surgical pathology was negative for lymphoma. Strongyloides serology was negative. Toxocara serology via ELISA test was negative. Toxoplasma IgG was 51 IU/mL (positive > 12 IU/ml). He was also noted to have elevated IgE 1659 IU/L. HIV viral load was undetectable. Stool ova and parasites test was negative as well as a gastrointestinal panel PCR. T and B cell panels were within normal limits.
Following inconclusive right axillary lymph node biopsy, he then underwent excisional biopsy of a right groin lymph node. On pathology, he was noted to have a benign reactive lymph node that was consistent with toxoplasmosis lymphadenitis (Figure 4 and 5). Bradyzoites were seen on pathology that confirmed the diagnosis. Aerobic, anaerobic, fungal and AFB cultures were negative as was cytology and flow cytometry. Rheumatology evaluation was negative as well.
Treatment and Follow Up
Patient was started on oral azithromycin, pyrimethamine and leucovorin for a six week duration. At the time of his last follow up, his lymphadenopathy and rash had completely resolved. He was referred to immunology and had an extensive immunologic workup performed. He had a normal T helper to suppressor cell ratio and did not have any immunoglobulin deficiencies.
Brief Discussion of Differential and Major Teaching Points of the Case
Toxoplasmosis is caused by infection with the protozoan Toxoplasma gondii, an obligate intracellular parasite. T. gondii has 2 distinct life cycles. The sexual cycle occurs only in cats, the definite host. The asexual cycle occurs in other mammals including humans. It consists of 2 forms: tachyzoites (the rapidly dividing form observed in the acute phase of infection) and bradyzoites (the slowly growing form observed in tissue cysts). T. gondii oocyts, tachyzoites and bradyzoites can cause infection in humans. Infection can occur by ingestion of oocysts following handling of contaminated soil or cat litter or through contaminated food or water sources1. Transmission can also occur via ingestion of tissue cysts (bradyzoites) in undercooked or uncooked meat or through transplantation of an organ that contains tissue cysts1. We suspect that our patient developed infection following ingestion of undercooked pork.
In an immunocompetent host, infection is generally self-limited. It may be asymptomatic or be a mild illness with fever, malaise and painless lymphadenitis. Patients can have single or multiple, generalized lymphadenopathy.2 Recently, “Amazonian Toxoplasmosis” has been described in immunocompetent individuals in French Guinea that resulted in aggressive and disseminated disease2.
Among immunodeficient individuals, toxoplasmosis often occurs in those with defects of T cell mediated immunity. These include patients with hematologic malignancies, bone marrow and solid organ transplants, or AIDS patients. In AIDS patients, T. gondii tissue cysts can reactivate with CD4 counts of less than 200 cells/uL. When counts are less than 100 cell/uL, clinical disease becomes more likely3. Patients with CD4 counts of less than 100 cells/uL with T. gondii IgG antibody positive have a 30% risk of eventually developing reactivation disease4. Reactivation is typically in the CNS although retinochoroiditis can be seen as well. Toxoplasma encephalitis and brain abscess presents as headache. Focal neurologic deficits and seizures are common as well. Cerebral toxoplasmosis is identified on head CT scan as multiple ring enhancing lesions however, solitary lesions can be seen as well. In the immunocompromised host, other conditions that have been identified include toxoplasma pneumonitis, myocarditis and disseminated toxoplasmosis.
Immunocompetent patients have an excellent prognosis. Lymphadenopathy and other symptoms resolve within weeks of infection. On the other hand, in immunodeficient patients, toxoplasmosis often relapses if treatment is stopped. Suppressive therapy and immune reconstitution reduces risk of recurrent infection. Of note, toxoplasma encephalitis can result in permanent neurologic sequelae depending on the location of the lesion.
Primary infection is acute and self-limited and does not warrant therapy in an immunocompetent, non-pregnant patient. One may elect to treat however if there is visceral involvement or symptoms are severe or persistent. In the immunocompromised patient with toxoplasma encephalitis, treatment is empiric with evidence of radiographic and clinical response to therapy in two weeks being supportive of the diagnosis. Preferred therapy is six weeks of oral pyrimethamine along with leucovorin and sulfadiazine5. Trimethoprim/ sulfamethoxazole can be an option in patients not able to take sulfadiazine and pyrimethamine. Azithromycin in combination with pyrimethamine has also been used.
Our patient was treated with a six week course of oral azithromycin along with pyrimethamine due to the severity of his symptoms. At six weeks follow up, lymphadenopathy had resolved and he was back to baseline.
- Opsteegh, M., Kortbeek, T. M., Havelaar, A. H. & van der Giessen, J. W. B. Intervention strategies to reduce human Toxoplasma gondii disease burden. Clin. Infect. Dis. 60, 101–107 (2015).
- Demar, M. et al. Acute toxoplasmoses in immunocompetent patients hospitalized in an intensive care unit in French Guiana. Clin. Microbiol. Infect. 18, E221–31 (2012).
- Luft, B. J. & Remington, J. S. Toxoplasmic encephalitis in AIDS. Clin. Infect. Dis. 15, 211–222 (1992).
- Porter, S. B. & Sande, M. A. Toxoplasmosis of the central nervous system in the acquired immunodeficiency syndrome. N. Engl. J. Med. 327, 1643–1648 (1992).
- Benson, C. A. et al. Guidelines for prevention and treatment opportunistic infections in HIV-infected adults and adolescents; recommendations from CDC, the National Institutes of Health, and the HIV Medicine Association/Infectious Diseases Society of America. (2009).
C. Salgado, None