A 50-year-old Latin American man presented with left peripheral facial palsy that resolved with a short oral corticosteroids course. Six days later, he developed progressive numbness in hands and feet and gait instability, followed by a right peripheral facial palsy. He had been diagnosed with HIV infection 7 months before and was receiving antiretroviral therapy, with an undetectable viral load and a CD4 count of 392. No other preceding infections were noted. The first neurological examination three weeks after the onset of symptoms revealed minimal right facial weakness, sensory deficits on vibration and proprioception, predominantly in lower limbs, areflexia, positive Romberg sign and mild gait ataxia. He was only able to walk a few steps with unilateral support (Hughes Score 3). Cerebrospinal fluid (CSF) study revealed a marked albumin-cytologic dissociation (963 mg/dL protein, 0 mononuclear cells) without evidence of malignant cells nor microbiological isolates. The initial suspected diagnosis was bifacial weakness with paraesthesias, a variant of Guillain-Barré Syndrome [9].
At four weeks from onset, his gait ataxia worsened, with inability to walk despite no motor impairment (Hughes Score 4), hence the patient was admitted to the hospital.
He also reported unspecified weight over last few weeks. Upon admission, he developed fever, hypotension, and tachycardia, and the blood tests showed an elevation of C-reactive protein and pancytopenia. The electrophysiological study revealed a sensory-motor axonal symmetric neuropathy with signs of demyelination in cranial segments (prolonged latency of R1 response in Blink reflex) (TABLE 1). Serum antiganglioside antibodies were negative, and brain and spinal MRI were unremarkable. Thrombocytopenia worsened to 25.000 platelets/µL, bone marrow aspiration was concordant with peripheral cytopenia, and abdominal ultrasonography showed splenomegaly. A whole-body PET/CT showed increased metabolic activity of multiple supra- and infra-diaphragmatic lymphadenopathies, the spleen, and bone marrow. A biopsy of an axillary lymphadenopathy revealed a lymph node characterized by small germinal centres, depleted of B-cells with penetrating vessels (lolly-pop pattern). The interfollicular areas showed an increase of plasma cells. Immunostaining showed HHV8-positive cells in the follicles, monotypic for lambda light chain and expressing IgM, whereas the interfollicular plasma cells were polytypic. No clonal population was detected by molecular studies. At the periphery of the lymph node, a vascular proliferation of spindle cells with HHV8+ endothelia was identified (FIGURE 1). POEMS syndrome was ruled out: monoclonal gammopathy was excluded by serum protein electrophoresis, serum and urine immunofixation, he had no endocrine or skin abnormalities, and VEGF levels were normal. The final diagnosis was multicentric Castleman disease with concurrent Kaposi sarcoma.
Chemoimmunotherapy was started, R-CHP without vincristine to avoid worsening the peripheral neuropathy, 8 weeks after symptom onset. Pancytopenia progressively resolved within 3 weeks. CSF study 6 weeks after clinical onset showed normal protein levels and negative cytology. The patient clinically improved over four weeks after starting treatment, and he was discharged with only dysesthesia in both hands without hypoesthesia and abolished patellar tendon reflexes. He was able to walk without support with a near-normal gait (Hughes Score 2). After completing 6 cycles of R-CHP over three months, the patient achieved complete remission of Castleman disease, with resolution of lymphadenopathies and splenomegaly. At the 6-month follow-up visit, he had completely recovered, the neurological exam was normal (Hughes Score 0), and a repeated electrodiagnostic study showed marked improvement of sensory and compound motor action potential (SNAPs and CMAPs) amplitudes, with resolution of the cranial demyelinating features (TABLE 1).