The patient is a 25-year-old male with a past medical history of asthma and childhood chickenpox who initially presented with a maculopapular rash involving the right leg and was clinically diagnosed with shingles. This was complicated by continued uncontrolled pain for which the patient was started on gabapentin and prednisone for suspected post-herpetic neuralgia. After a few weeks, the patient presented again with blistering rashes progressing to the arms, legs, and face (Fig. 1). The rash was sudden in onset followed by small nodular lesions approximately 24 hours later. He also reported a 3-day history of diaphoresis, dizziness, loose stools, and loss of taste sensation. In the ED, he tested positive for COVID-19. Due to high-risk sexual history, he was also tested for HIV with a 4th gen HIV antigen/antibody test, which returned positive. With the new diagnosis of HIV, COVID-19, and the rash, he was admitted to the hospitalist service, and infectious disease was consulted.
Of note, the patient reported that his last sexual contact was approximately 6 months prior. He stated that he prefers male partners and usually participates in anal insertive intercourse. He also mentioned that he previously participated in anal receptive intercourse. He mentioned that he does not use condoms consistently. He did not get any vaccines against COVID-19.
In the hospital, HIV RNA was detected at 999,908 viral copies/mL and the CD4 count of zero. On further examination, it was also noted that the patient had vesicular lesions in different stages of development affecting his eyelid and it was difficult to fully open his eye due to the swelling (Fig. 1. e). Disseminated Varicella Zoster with zoster ophthalmicus was suspected. A punch biopsy of the skin lesion was obtained and Tzanck smeared to confirm the lesions were herpetic in nature. Tzanck smear showed intracorneal necrosis and debris with viral cytopathic effect. Intravenous acyclovir 10mg/kg every 8 hours was started for disseminated Varicella-Zoster and ophthalmology was consulted. Eye examination revealed ocular involvement with a hazy cornea (keratitis), elevated intraocular pressure (HZO glaucoma), and intraocular inflammation (uveitis). The ophthalmologist started polysporin brimonidine, cyclopentolate, and latanoprost eye drops for zoster ophthalmicus.
The patient had ongoing oxygen requirements on the floor. A chest X-Ray showed infiltrates concerning for COVID-19 pneumonia. He was started on dexamethasone and baricitinib. Infectious disease recommended postponing the initiation of anti-retroviral therapy (ART) at that stage and treating acute COVID-19 first. He was started on Mycobacterium avium and PJP prophylaxis with azithromycin 1200mg weekly and trimethoprim-sulfamethoxazole, respectively.
Unfortunately, the patient had an unwitnessed fall and was found down on the floor by the side of his bed by a nurse. The patient was found to be awake but confused. A CT head demonstrated left-sided subdural hematoma measuring up to 3 mm in thickness with mild mass effect in the left cerebral hemisphere and a remote left parietal infarction. Neurosurgery was consulted and recommended withholding surgical intervention at that time. The patient had progressive worsening hypoxia and had a sudden increase in O2 supplementation, with his O2 requirement going from nasal cannula to a non-rebreather and Optiflow in a few minutes. He was intubated and transferred to the intensive care unit (ICU) where he required mechanical ventilation and vasopressor support. Echocardiography demonstrated a hyperdynamic left ventricle with an ejection fraction of 70% and an elevated right ventricular systolic pressure at 65–70 mm Hg. A CT angiogram chest showed multifocal pulmonary emboli with a significant embolic burden with evidence of right heart strain. The CTA chest also reported patchy and nodular parenchymal opacities along with focal parenchymal nodularity with possible infectious and/or inflammatory sequela. Initially, anticoagulation was held due to the presence of subdural hematomas. However, following further discussion with neurosurgery intravenous heparin was cautiously started. Given the patients massive pulmonary embolism, the benefits outweighed the risks. The patient's subdural hematoma was monitored with serial CT head while he was on intravenous heparin, and it remained stable. In the ICU, the patient became febrile and tachycardic. A pan culture was obtained, and the patient was empirically started on vancomycin and piperacillin-tazobactum. A lumbar puncture was considered but was not done at this time due to low platelets. At this time, he was started on highly active antiretroviral therapy (HAART) with Biktarvy (bictegravir / emtricitabine/tenofovir alafenamide) by infectious disease. Antibiotics were discontinued after 2 days as cultures did not show any bacterial growth. He self-extubated during a coughing episode after 10 days of intubation.
He was later transferred to the intermediate unit as his respiratory status remained stable on oxygen via nasal cannula. Two days later, the patient was noted to have worsening encephalopathy with fever, tachycardia, and tachypnea. There was a concern for IRIS (immune reconstitution inflammatory syndrome. Repeat cultures were sent and the patient was started on vancomycin and piperacillin-tazobactum. Procalcitonin was low at 0.08 and the chest x-ray was clear making IRIS less likely.
A repeat CT head was suggestive of an interval increase in his SDH with increased midline shift. Neurosurgery was consulted and recommendations were made to take the patient to the OR for burr hole and SDH evacuation. CSF fluid was obtained during the burr hole procedure. CSF showed pleocytosis with encephalitis panel (AFB, fungal, bacterial, and cryptococcal antigen, viral) positive for both CMV (cytomegalovirus) and VZV. Blood was also positive for both CMV and VZV. Given that the patient had received a prolonged course of acyclovir, treatment was switched to intravenous ganciclovir (5 mg/kg IV every 12 hours), which covers both CMV and VZV. A follow-up CTA head showed multifocal irregularity and narrowing of bilateral MCA, ACA, and PCA branches including the distal right M1 and distal right A1 segments (Fig. 2), consistent with vasculitis which can be seen in both VZV and CMV. Intravenous methyl prednisone was started at 1 gram daily for 5 days to treat the CNS vasculitis. For CMV CNS disease there are no clear guidelines on the optimal length of therapy, but infectious disease recommended 2 weeks of intravenous ganciclovir. Repeat LP after 2 weeks showed a drastic drop in CMV.
During the hospitalization, the patient remained paraplegic. Differential diagnoses included critical illness myopathy, VZV/CMV induced myelitis, and HIV myelopathy. Thoracic spine MRI showed multifocal patchy and discontinuous signal abnormalities within the thoracic cord (Fig. 3). Similar findings are seen in HIV vacuolar myelopathy and nonspecific demyelination. The patient was transferred to inpatient rehabilitation and he continued to gradually recover his motor activities. His mobility remained impaired and he required assistance with activities of daily living. Three months after initiating HAART, his HIV viral count decreased from 596,000 copies per mL to 124 copies per mL and his CD4 count increased from 0 to 10 cells per cubic mm.