The absence of typical pneumonia symptoms in a patient with rheumatoid arthritis during tocilizumab and steroid treatment

Abstract

A 78-year-old woman with rheumatoid arthritis while being treated with tocilizumab and steroid treatment presented with pharyngeal pain and general malaise. She felt chills and vomited while waiting in the waiting room, in addition to urinary incontinence. An immediate evaluation of her condition indicated that she was in shock and a physical examination revealed moist rales in the right lung field. Her white cell count and C reactive protein level were within normal limits; however, a radiological study indicated pneumonia. Antibiotic treatment resulted in improvement of her condition. Blood culture later revealed bacteraemia due to Streptococcus pneumoniae. The anti-inflammatory effect of tocilizumab and steroid treatment may mask the typical symptoms and signs of infection, so physicians must be aware of the potential for hidden infection when such patients present with an unidentified complaint.

Background

The anti-inflammatory effect of tocilizumab and steroid treatment may mask the typical symptoms and signs of infection, so physicians must be aware of the potential for hidden infection when such patients present with an unidentified complaint.

Case presentation

A 78-year-old woman noticed pharyngeal pain 3 days before arrival at a medical facility. Her previous history included rheumatoid arthritis for 38 years and hypertension for 10 years. She had been treated with 1 mg of methylprednisolone and 80 mg/4 weeks of tocilizumab for rheumatoid arthritis. She gargled with an iodine based disinfectant; however, the pain did not improve and she felt general malaise. She returned to the medical facility and waited in the waiting room with no cough, dyspnoea or fever. Thereafter, she felt chills and vomited, accompanied by urinary incontinence. An immediate evaluation of her condition indicated that she was in shock and a physical examination revealed moist rales in the right lung field.

Investigations

Electrocardiogram did not indicate ischaemic change. Cardiac sonography revealed hyperkinetic wall motion. Whole body CT showed a high density area in the right lung field compatible with pneumonia (figure 1). The results of blood biochemical analyses were: white blood cell count, 9100/μl (3500–9100/μl is within the normal limit in this institute); C reactive protein (CRP), <0.3 mg/dl. She was diagnosed with acute respiratory distress syndrome and septic shock induced by pneumonia.

Figure 1.

Chest CT on arrival. Chest CT demonstrates a high density area in right lung field, suggesting pneumonia.

Treatment

She received onxygen, antibiotics, methylprednisolone and γ-globlin.

Outcome and follow-up

Her respiratory function thereafter improved on the second hospital day. The results of her blood biochemical analyses were: white blood cell count, 22700 μ/l and CRP 5.8 mg/dl. A subsequent blood culture was positive for Streptococcus pneumoniae. Her pneumonia was cured and discharged on the 34 hospital day.

Discussion

Interleukin 6 (IL-6) is a cytokine that plays an important role in immune responses and is implicated in the pathogenesis of many diseases, such as autoimmune diseasess. The discovery that several proinflammatory cytokines such as IL-6 act as endogenous pyrogens provides a link between the immune and the central nervous systems.¹ The level of IL-6 is correlated with the signs of fever, chills and minor fatigue in patients with refractory advanced malignancies.² Tocilizumab binds soluble as well as membrane bound IL-6 receptors, hindering IL-6 from exerting its pro-inflammatory effects. Tocilizumab was approved in Japan for Castleman’s disease in 2005 and for rheumatoid arthritis in 2008 because IL-6 plays a significant pathological role in these diseases. We present here a case of absence of typical pneumonia symptoms in a patient with rheumatoid arthritis during tocilizumab and steroid treatment.

Fujiwara et al reported two cases of patients who developed severe pneumonia during tocilizumab and steroid treatments for rheumatoid arthritis.³ Both patients had severe bacterial pneumonia and later developed septic shock, on the first day they initially presented with only minimal clinical symptoms and modest elevations in serum CRP. Such symptoms as fever, chills, cough and minor fatigue induced by bacterial infection may be masked by treatment with tocilizumab through an anti-IL-6 effect. Accordingly, tocilizumab might suppress the early inflammatory symptoms of pneumonia. IL-6 plays a role in the production of CRP when the patient has an infection so that tocilizumab may suppress elevation of CRP when an infection occurs.⁴ CRP has a protective effect against fatal S pneumoniae infection in transgenic mice so that either a delay or the suppression of the production of CRP may induce an immediate deterioration of a bacterial infection.⁵ In addition, the combination treatments of tocilizumab and steroid for rheumatoid arthritis increase occurrence of infection including pneumonia;⁶ therefore physicians should be aware of the potential for hidden severe infection and rapid deterioration when patients are treated with such drugs.

Learning points.

• The typical symptoms and sign of infection may be masked by the anti-inflammatory effect of tocilizumab and steroid treatment; therefore physicians should be aware of the potential for hidden severe infection and rapid deterioration when patients are treated with such drugs.