EUHM Report: Acute and subacute shortness of breath in patients with Pneumocystis Jirovecii Pneumonia

HIV-infected patients usually develop a subacute course of disease, while non-HIV infected immunocompromised patients are characterized by a rapid disease progression with higher risk of respiratory failure and higher mortality. The main symptoms usually include exertional dyspnea, dry cough, and subfebrile temperature or fever.

Salzer, Helmut J F, Guido Schäfer, Martin Hoenigl, Gunar Günther, Christian Hoffmann, Barbara Kalsdorf, Alexandre Alanio, and Christoph Lange. “Clinical, Diagnostic, and Treatment Disparities between HIV-Infected and Non-HIV-Infected Immunocompromised Patients with Pneumocystis Jirovecii Pneumonia.” Respiration. 96, no. 1 (2018): 52-65.

The diagnosis of PCP is mostly a presumptive diagnosis in resource-limited settings. Clinical signs and symptoms, particularly dyspnea, fever, dry cough, and hypoxia in absence of an alternative diagnosis in an immunocompromised patient with a CD4+ T lymphocyte count <200 cells/mL and concurrent radiological changes lead to the initiation of PCP treatment

Table 1. Disease characteristics of PCP in HIV-positive patients compared to patients with other reasons of immunosuppression (page 4)




VA Resident Report: What is the management strategy of Kaposi Sarcoma and pneumocystis pneumonia in a HIV positive patient?

The Bottom Line:

The management of pulmonary KS is challenging. There is a risk of precipitating IRIS upon initiating cART. Chemotherapy can also cause further immunosuppression and increase the risk of further infections. In many of these patients, initiation of cART with careful monitoring for IRIS and empiric treatment of suspected infections may be the best therapeutic option. In some patients, there was a hesitancy to start cART if there was a history of poor medication adherence. Many of these patients required prolonged hospitalization, where their adherence could have been carefully monitored and encouraged.

Kasturia, S., Gunthel, C., Zeng, C., & Nguyen, M. (n.d.). Severe Kaposi Sarcoma in an Urban Public Hospital. AIDS Research and Human Retroviruses, 33(6), 583-589.

The majority of patients were highly immunosuppressed when KS was diagnosed (median CD4 count: 11), and 68% had multiple organ involvement with KS. Comorbidities at diagnosis included hepatitis B (26%) and pneumocystis pneumonia (33%). Frequent reasons for admission included skin and soft tissue complaints (28.4%) and respiratory complaints (27.2%). The estimated median survival after KS diagnosis was 3.0 years. Lung involvement, liver involvement, poor performance status, and low CD4 T cell count (<50) were associated with lower survival.

EUHM Resident Report: What is the correlation of HSV encephalitis and intracerebral hemorrhage?

The mechanism of hemorrhagic complication in HSV encephalitis is unclear. The possible mechanisms  include small vessel rupture due to vasculitis and transient hypertension caused by increased intracranial pressure. Gyral pattern of the hemorrhage may suggest that the hemorrhagic complication in HSV encephalitis may be due to associated vasculitis

Takeuchi, S., & Takasato, Y. (n.d.). Herpes simplex virus encephalitis complicated by intracerebral hematoma. Neurology India., 59(4), 594-596.

Herpes simplex virus (HSV) encephalitis is the most common cause of sporadic encephalitis, with a mortality of 70% if untreated. Treatment with acyclovir is associated with reduced mortality. Petechial cortical hemorrhages are common in HSV encephalitis, whereas frank hematoma is extremely rare; only 10 cases have been reported in the literature.


Intracerebral hematoma can complicate HSE even when the evolution is favorable. It should be suspected whenever neurologic deterioration appears and should be distinguished from acyclovir resistance and toxicity, since the management of these entities differs substantially.

Rodríguez-Sainz, A., Escalza-Cortina, I., Guio-Carrión, L., Matute-Nieves, A., Gómez-Beldarrain, M., Carbayo-Lozano, G., & Garcia-Monco, J. (2013). Intracerebral hematoma complicating herpes simplex encephalitis. Clinical Neurology and Neurosurgery, 115(10), 2041-2045.

Intracranial bleeding, although infrequent, can complicate the evolution of herpes simplex encephalitis and should be borne in mind since its presence may require neurosurgery. Although its presentation may overlap the encephalitic features, the lack of improvement or the worsening of initial symptoms, particularly during the second week of admission, should lead to this suspicion and to perform a neuroimaging study.


HSV enters the brain through the direct neuronal transmission from the peripheral site to the brain through the trigeminal or olfactory nerve. The usual manifestation of HSE is fever, headache, seizures, and change in mental status evolving over several days. Atypical manifestation includes intracerebral hemorrhage which has been reported mainly in infants and young children. Intracerebral hematoma in HSE in adults is rare. There are some reports of the occurrence of hematoma in HSE in the adults. The exact mechanism of hemorrhage in HSE is unclear. Vasculitis causing small vessel rupture and transient hypertension due to raised intracranial pressure has been proposed for hemorrhage in HSE.

Mahale, R., Mehta, A., Shankar, A., Miryala, A., Acharya, P., & Srinivasa, R. (2016). Bilateral Cerebral Hemorrhage in Herpes Simplex Encephalitis: Rare Occurrence. Journal of Neurosciences in Rural Practice., 7(Suppl 1), S128-S130.

The most frequent cause of sporadic encephalitis is herpes simplex encephalitis (HSE). It carries a mortality of 70% if left untreated. With the usage of acyclovir in the management of HSE and early diagnosis, the mortality rate has been reduced to 19%. Herpes simplex virus (HSV) causes hemorrhagic necrotizing encephalitis involving the frontal and medial temporal lobes. Petechial cortical hemorrhages have been reported in HSE; however, frank hematoma is rare.

EUHM Resident Report: How is hypokalemia associated with HIV?

The Bottom Line: Adverse events in HIV patients taking tenofovir are relatively rare, postmarketing reports of nephrotoxicity have alerted physicians to other potentially serious outcomes. This study presents a series of 40 patients who developed hypokalemia associated with tenofovir. Identified risk factors included concomitant ritonavir or didanosine use, a lower weight and longer duration of tenofovir use.

References: Cirino, C., & Kan, V. (n.d.). Hypokalemia in HIV patients on tenofovirAIDS.,20(12), 1671-1673.

Summary: Table 1. Summary of demographic and clinical data from our patient and 39 individual safety reports for hypokalemia on tenofovir.

The overall incidence of toxicity with tenofovir is low. Risk factors of developing renal insufficiency or failure while on tenofovir include those with low body weight, baseline renal insufficiency, or regimens containing ritonavir and didanosine.

VA Resident Report: How does acute retroviral syndrome result in rhabdomyolysis?

The Bottom Line: More recent studies highlight an increased incidence of HIV associated thrombotic microangiopathies and rhabdomyolysis, the latter from the use of statins in combination with highly active anti-retroviral therapy (HAART)

References: Prabahar, M., Jain, M., Chandrasekaran, V., Indhumathi, E., & Soundararajan, P. (n.d.). Primary HIV infection presenting as non-traumatic rhabdomyolysis with acute renal failureSaudi Journal of Kidney Diseases and Transplantation : An Official Publication of the Saudi Center for Organ Transplantation, Saudi Arabia., 19(4), 636-642.

Summary: The term rhabdomyolysis refers to disintegration of striated muscle, which results in the release of muscular cell constituents into the extra cellular fluid and the circulation. One of the key compounds released is myoglobin, an 18,800-Dalton oxygen carrier. Normally, myoglobin is loosely bound to plasma globulins and only small amounts reach the urine. When massive amounts of myoglobin are released, the binding capacity of the plasma protein is exceeded. Myoglobin is then filtered by the glomeruli and reaches the tubules, where it may cause obstruction and renal dysfunction

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VA Resident Report: Is there an increased risk for patients with Terminal Complement Deficiency and HIV?

The Bottom Line: The Advisory Committee on Immunization Practices has previously recommended routine vaccination of persons aged ≥2 months who have certain medical conditions that increase risk for meningococcal disease, including persons who have persistent deficiencies in the complement pathway (e.g., C3, properdin, Factor D, Factor H, or C5–C9); persons receiving eculizumab (Soliris, Alexion Pharmaceuticals) for treatment of atypical hemolytic uremic syndrome or paroxysmal nocturnal hemoglobinuria (because the drug binds C5 and inhibits the terminal complement pathway)

MacNeil, J., Rubin, L., Patton, M., Ortega-Sanchez, I., & Martin, S. (2016). Recommendations for Use of Meningococcal Conjugate Vaccines in HIV-Infected Persons – Advisory Committee on Immunization Practices, 2016. Morbidity and Mortality Weekly Report MMWR /, 65(43), 1189-1194.

In addition, ACIP recommends routine vaccination with serogroup B meningococcal (MenB) vaccine for persons who have persistent complement component deficiencies; persons who have anatomic or functional asplenia; microbiologists who routinely are exposed to isolates of N. meningitidis; and persons identified to be at increased risk because of a serogroup B meningococcal disease outbreak.