Castleman disease is a
lymphoproliferative disorder characterized by atypical lymph node
hyperplasia and systemic symptoms; it can also affect the skin and blood counts. The condition is categorized by the extent of involvement (unicentric or multicentric) and the observed lymph node pathology (hyaline-vascular, plasma cell or mixed cellularity). Pathogenesis also has a role in the classification and treatment of multicentric
Castleman disease; this variant can either be related to the presence of human herpesvirus-8 (HHV-8) infection or associated with POEMS (
polyneuropathy, organomegaly, endocrinopathy, monoclonal
proteins and skin changes) syndrome, or idiopathic. The principal
cytokine responsible for causing idiopathic multicentric
Castleman disease (IMCD) is
interleukin-6 (IL-6). Therefore, treatment with agents that bind to
IL-6 (such as
siltuximab) or block the
IL-6 receptor (such as
tocilizumab) has been used. We report a woman with IMCD who was successfully being treated with
siltuximab; her cutaneous manifestations and systemic
disease (lung and lymph nodes) improved within three months. However, nine months after starting
siltuximab, she developed a worsening
cough and new infiltrates in the right lung on positron emission tomography/computed tomography (PET/CT) scan; there were no other constitutional symptoms such as
fever, night sweats or
fatigue. Differential diagnosis included
Castleman disease recurrence,
lung neoplasm and
infection. Her pulmonary symptoms and infiltrates on scan resolved
after treatment with systemic
levofloxacin, indicating that she had an
antibiotic-sensitive afebrile
pneumonia. We postulate that her
siltuximab therapy blocked the IL-6-associated
fever and constitutional symptoms that normally are a hallmark of
pneumonia. Therefore, patients who are receiving medications such as
siltuximab and
tocilizumab that block the
IL-6 pathway and impair the acute phase inflammatory response may fail to manifest constitutional symptoms such as
fever when infected.