Our case raises awareness for the risk of vaccine-induced ELS, especially in patients with a history of recurrent pneumococcal disease and thus partial immunity

Our case raises awareness for the risk of vaccine-induced ELS, especially in patients with a history of recurrent pneumococcal disease and thus partial immunity. Introduction Invasive pneumococcal infection has a high morbidity and mortality,1 often preventable by a single vaccination with the pneumococcal conjugate vaccine (PCV).2 The Capita trial indicating vaccine-conferred protection from community-acquired pneumonia (CAP) in immunocompetent elderly extended the use of PCV beyond patients with chronic disease.2,3 The 13-valent conjugate pneumococcal vaccine (PCV13) contains the capsular polysaccharides (PS) of 13 serotypes at 25?g each. subdermal infiltration dominated by CD4+ T cells and macrophages. In a multiplexed serotype-specific measurement of the anti-pneumococcal IgG response, the patient showed very broad and strong vaccine responses. Pre-vaccination titers were low for the vaccine serotypes. We did not find in vivo nor in vitro evidence of an excessive T cell response to the diphtheria-derived PCV carrier protein. However, we could demonstrate a high antibody titer to a non-vaccine serotype, indicating in vivo pre-exposure to pneumococcus bacteria. Thus, traces of pneumococcal proteins included in PCV13 may have boosted pre-existing pneumococcus-specific T helper cells, which subsequently orchestrated ELS. Our case raises awareness for the risk of vaccine-induced ELS, especially in patients with a history of recurrent pneumococcal disease and thus partial immunity. Introduction Invasive pneumococcal contamination has a high morbidity and mortality,1 often preventable by a single vaccination with the pneumococcal conjugate vaccine (PCV).2 The Capita trial indicating vaccine-conferred protection from community-acquired pneumonia (CAP) SAR125844 in immunocompetent elderly extended the use of PCV beyond patients with chronic disease.2,3 The 13-valent conjugate pneumococcal vaccine SAR125844 (PCV13) contains the capsular polysaccharides (PS) of 13 serotypes at 25?g each. These are covalently bound (conjugated) to a diphtheria toxoid carrier protein CRM197. This carrier protein is processed by dendritic cells and PS-specific B cell and presented to CD4+ T helper cells.4 Upon activation these provide activation signals to the PS-specific B cells thereby enhancing antibody class switch and memory formation. Extensive inflammatory skin reactions at the vaccination site, also known as extensive limb swelling (ELS),5 have been described following PCV6 and pneumococcal polysaccharide vaccine (PPV).7C10 However, since pre-existing immunity at the time of vaccination is usually unknown, there are no immune system correlates known to predispose to such reactions. In addition, it is not clear whether such reactions and/or the anti-inflammatory treatment they require are associated with strong or impaired humoral vaccine responses. Results Here we report an extensive inflammatory skin reaction that occurred at the site of vaccination in a 67-year-old Caucasian woman following a single dose of PCV13 (Fig. ?(Fig.1).1). Prior to PCV vaccination she underwent a detailed immunological work-up at our immunodeficiency clinic because of recurrent lower respiratory tract infections. Over the past 6 years, she experienced three CAP, once with sepsis. Bacterial blood cultures and search of urinary pneumococcal and legionella antigens were performed after initiation of antibiotic therapy. No causative agent could be isolated for any of the three episodes. Patient history was remarkable for two episodes of diverticulitis, recurrent herpes labialis (cold sore; reactivation rate 1/year11 and not for several months preceding PCV administration), obesity (BMI 39?kg/m2), and non-insulin-dependent diabetes mellitus. No opportunistic infections were documented. She was not taking any immunosuppressive drugs. She had been vaccinated according to the Swiss vaccination guidelines.12 The last tetanus/diphtheria booster dose had been administered 17 years ago. She had never received any pneumococcal vaccine. The physical examination and CT scan imaging were normal, with no evidence for chronic pulmonary disease or lympho proliferation. Body pletysmography was DP1 normal, excluding asthma or chronic obstructive lung disease. Immunologic analysis in the clinical routine showed normal total serum IgG, IgM, IgA, and IgG1C4 subclass levels. Lymphocyte (T vs. B vs. SAR125844 NK cell) and B cell subset distribution (naive vs. memory vs. marginal zone-like B cells) were normal (Table ?(Table1).1). Functional complement screening revealed normal classical and alternative pathways (Table ?(Table1).1). In summary, there was no evidence of an underlying immunodeficiency that would have predisposed to the SAR125844 recurrent infections. Diabetes and obesity were potential risk factors. Open in a separate window Fig. 1 Strong local injection site reaction 4 days following PCV13 vaccination. a Circle indicates biopsy site, asterisk indicates the vaccine injection was done. b Skin biopsy shows infiltration of mononuclear cells, mostly consisting of CD4+ T cells and CD68+ macrophages, while B cells were virtually absent. Scale bar indicates 100?m. c Serotype-specific IgG responses pre-vaccination (open bars) and 4 weeks post-vaccination (black bars) toward vaccine and non-vaccine strains. Values below lower detection limit ( 0.3?mg/L) were set to 0.3?mg/L. d Pre-PCV vaccination titers against tetanus and diphtheria were low/undetectable. Post-PCV vaccination diphtheria titers (i.e., anti-carrier protein) were high Table 1 Basic immunological work-up.