PMC7493652_01
Diagnostic work-up and treatment regimes in an alemtuzumab-treated patient with relapsing-remitting multiple sclerosis developing AOSD. (A) Varicella-zoster virus-induced left ophthalmic zoster. (B) Sagittal fluid-attenuated inversion recovery of the brain demonstrating multiple non-enhancing T2 hyperintense lesions. One new, non-enhancing lesion is indicated by an arrow. (C) Evanescent maculopapular, salmon-pink skin rash on the right arm. Charts show the course of white blood cell counts and neutrophils (D), CRP (E), platelets (F), ferritin (G), and amyloid (H). Time points and length of different treatment regimens are outlined : single administration of IVMPS; : three doses of IVMPS on three consecutive days; : three doses of intravenous immunoglobulins on three consecutive days; arrows indicate the duration of therapies with anakinra (A) and rituximab (R). (I) FDG-PET/CT showing significant hypermetabolism in bone marrow and spleen. Hematoxylin and eosin staining of skin biopsy displaying periadnexal and perivascular infiltrates of inflammatory cells, surrounding superficial blood vessels, hair follicles, and the interstitium (in between the vessels and adnexal structures). Original magnification at 200 mum (J). Hematoxylin and eosin stain showing perivascular inflammatory infiltration of lymphocytes, neutrophils, and eosinophils. Original magnification at 50 mum (K). Generalized drug eruption on the back, chest area, arms, and legs due to therapy with anakinra (L).
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In February 2017, the patient suffered from varicella-zoster virus-induced left ophthalmic zoster (Figure 1A), which was treated with intravenous aciclovir. Disease activity stabilized clinically over time, but cranial magnetic resonance imaging from April and October 2017 showed three new, non-enhancing T2 hyperintense lesions in the left operculum and periventricular (Figure 1B). 2 months after the second course of alemtuzumab, the patient presented to her local ear, nose, and throat (ENT) clinic with a sore throat and swallowing difficulties. The patient further suffered from high spiking quotidian fever of up to 40 degrees occurring in the evenings, and a generalized itching, evanescent maculopapular, salmon-pink skin rash (Figure 1C) that accompanied the fever. Under single dose of intravenous methylprednisolone (IVMPS, Figures 1D,E) and antihistamines, the rash improved only temporarily. She developed anemia, neutrophilic leukocytosis, and thrombocytosis, and showed elevated acute-phase reactants (Figures 1D-F) including amyloid, interleukin-2 (1654 U/ml; reference value < 623 U/ml), and interleukin-6 levels (61.8 pg/ml; reference value < 7 pg/ml). Following a probatory IVMPS therapy (three doses; Figures 1D,E) and subsequent oral prednisolone with slow dose tapering, symptoms improved, and inflammatory blood parameters decreased. When trying to reduce oral prednisolone, the symptoms came back, and inflammatory blood parameters and platelets immediately increased (Figures 1D-G). Therapy with the anti-IL-1 agent (anakinra), initiated in April 2018, led to a significant improvement of symptoms and blood parameters (Figures 1D-H). However, anakinra had to be discontinued after 4 weeks due to generalized itching and follicular drug eruption (Figure 1L). Whole-body 18F-FDG-PET/CT demonstrated significant hypermetabolism in bone marrow and spleen (Figure 1I). Therapy termination led to a massive deterioration of symptoms and anemia, and an increase of acute-phase reactants, leukocytes, neutrophils, ferritin and amyloid (Figures 1D-H). Repeated IVMPS and oral prednisolone with slow dose tapering, intravenous immunoglobulins (Figures 1D-H,), and initiation of rituximab therapy (Figures 1D-H) induced ongoing remission.