A 37-year-old Chinese man presented to our hospital in April 2020 with red, swollen eyes, acute worsening exophthalmos, and intermittent diplopia sustained for 7 days. A year earlier, he had been diagnosed with HIV-1 and had started ART [lamivudine (3TC) 300 mg daily, tenofovir disoproxil 300 mg daily, and dolutegravir 50 mg daily] regimen. Following the ocular symptoms, the tenofovir disoproxil and dolutegravir were replaced with lopinavir/ritonavir 400 mg/100 mg twice a day and zidovudine (ZDV) 300 mg twice a day at another hospital one week before this visit. His nadir CD4+ T cell count was 242 cells/mul, which increased to 717 cells/mul at the time of examination. His HIV RNA load was less than 20 copies/ml. He was afebrile. An ophthalmologic examination showed proptosis, congested, and edematous conjunctivae, protruding beyond the lid margin, without ptosis. His corneas, fundi, and visual acuity were normal ( Figure 1A ), though his eyeball mobility was limited bilaterally. The patient had no personal or family history of autoimmune disease.
Orbital computed tomography (CT) confirmed that both eyes were slightly protruding. The extraocular muscles, especially the superior and inferior recti, were enlarged bilaterally ( Figures 2A-C ). The optic nerves were normal. Ocular color ultrasound imaging showed mild, bilateral vitreous opacities and widening of the superior ophthalmic veins. Brain magnetic resonance imaging (MRI) showed no parenchymal abnormality. Contrast-enhanced MRI revealed thickening and increased signal intensity of the extraocular muscles, including the tendinous insertions. Both eyelids and lateral soft tissues showed diffuse swelling, without the lacrimal gland and periorbital fat involvement ( Figures 2D-F ). Aztreonam and clindamycin intravenous antibiotics were administered for 3 days; nonetheless, there was no clinical improvement.
Graves' orbitopathy (GO) was initially suspected. However, thyroid function tests involving measurements of triiodothyronine; thyroxine, thyroid stimulating hormone, thyroglobulin, thyroid peroxidase, and thyrotropin receptor antibodies as well as color-flow Doppler sonography scan, were normal. Further blood results included the following: serum immunoglobins [IgA, 4.03 g/L (range 0.7-3.8 g/L), IgG, 12.39 g/L (7-17g/L), IgM, 1.89 g/L (0.6-2.5 g/L)] and antibody tests (1:100-positive antinuclear antibody and negative antineutrophil cytoplasmic antibody). The orbital involvement in immunoglobulin G4-related disease (IgG4-RD) was excluded due to normal serum IgG4 levels, absence of eosinophilia (leukocyte 9.39 x109/L, eosinophilia 0.42 x109/L), and lack of lacrimal gland involvement. Serum antibody tests for herpes simplex virus, varicella-zoster virus, cytomegalovirus, toxoplasma, and syphilis were negative. Serum Epstein-Barr virus-DNA was absent, and the blood T-SPOT. TB assay to detect T cells primed to mycobacterium tuberculosis (TB) infection was negative. Finally, a diagnosis of IRIS-associated orbital myositis (IRIS-OM) was considered. Dexamethasone (5 mg) was administered intravenously for 5 days, followed by oral prednisone (30 mg) daily. The patient's proptosis, diplopia, and limited ocular movements improved considerably ( Figures 1B, C ) with an MRI of the extraocular muscles showing reduced swelling ( Figures 2G-I ).
Three months later, when tapering the prednisone, the patient presented with left ptosis, followed immediately by bilateral ptosis and diplopia ( Figures 1D, E ). He complained of facial muscles' weakness when chewing and weakness of both upper limbs' muscles while driving. Neurological examination showed bilateral ptosis and disconjugate eye movements without detectable facial or upper limb muscles' weakness. His sensation, coordination, and deep tendon reflexes were normal. A neostigmine challenge test was positive. Further blood tests showed a positive result for the ryanodine receptor (RyR). Acetylcholine receptor (AChR), muscle-specific tyrosine kinase (MuSK), and titin receptor antibodies were negative. Creatine kinase levels were within normal limits (105 U/L; normal range 39-308 U/L). A chest CT scan results excluded thymus abnormalities. Routine nerve conduction studies of the right facial nerve, left ulnar nerve, and left median nerve were normal. Low frequency and high frequency repetitive nerve stimulation using the standard approach was used to evaluate the left ulnar nerve and right facial nerve. The left ulnar nerve demonstrated normal responses, whereas the right facial nerve demonstrated 15% decrement in amplitude at low frequencies without enhancement at high frequencies. Single fiber electromyography (EMG) and needle EMG were not performed. Based on the outlined findings, the patient was diagnosed with probable IRIS-associated MG. He was treated with oral pyridostigmine bromide, 60 mg three times per day; tacrolimus, 1 mg twice a day; prednisone, 30 mg once a day for 2 weeks, followed by 20 mg daily for 3 months. One month later, the patient showed considerable improvement ( Figure 1F ); facial and upper limb muscle weakness improved more rapidly than the ptosis. At the time of this report, the serum creatine kinase was 33 U/L (39-308 U/L), the CD4+ T cell count had dropped to 369 cells/mul, and the HIV RNA load was undetectable. He had no complaints with the current pyridostigmine bromide (60 mg daily), prednisone (20 mg daily), and tacrolimus (2 mg daily) treatment regimen, together with ART ( Table 1 ).