Immunosuppression Related to Collagen-Vascular Disease or Its Treatment

Abstract

Collagen-vascular diseases are associated with immune dysregulation and inflammation, leading to tissue destruction or compromise. Immunosuppression is more commonly associated with the drugs used to treat these disorders than with the diseases themselves. The newest agents being used to treat collagen-vascular diseases are the tumor necrosis factor (TNF)-␣ inhibitors. U.S. Food and Drug Administration-approved TNF-␣ inhibitors have differing effects on the immune system, reflecting their potency and mechanisms of action. They are particularly effective in breaking down granulomatous inflammation, which makes them effective treatment for sarcoidosis and Wegener's granulomatosis. This same property makes them likely to break down the host defense mechanism that normally contains pathogens such as mycobacteria and fungi in a dormant state, namely the physical and immunologic barrier formed by granulomas in the lung and elsewhere. The most common infection reported with the TNF-␣ inhibitors has been tuberculosis, which may manifest as pulmonary and/or extrapulmonary disease, with the latter being more common and severe than usual. Histoplasma capsulatum, Aspergillus, Cryptococcus neoformans, and Listeria monocytogenes have also been described in a number of cases, and their frequency is discussed.

Thoracic Manifestations of Connective Tissue Diseases

“…Although intrinsic immunologic abnormalities predispose the patient to nonspecific infections (such as community-acquired pneumonia in SLE and aspiration pneumonia in SSc), severe immunosuppression related to several therapeutic agents (e.g., corticosteroids, methotrexate, and cyclophosphamide) might lead to atypical or more severe pulmonary and systemic infections. 47 As such, patients with SLE under immunosuppressive treatment may present infections to mycobacteria (Fig 18), Pneumocystis jirovecii, cytomegalovirus, Aspergillus species, and Nocardia. 1,23 Likewise, patients with RA, especially those under treatment with TNFα inhibitors, are susceptible to opportunistic microorganisms such as Mycobacterium tuberculosis, Listeria monocytogenes, and P. jirovecii.…”

Listeriosis: a primer

“…Individuals taking tumour necrosis factor inhibitors and transplant recipients taking anti-rejection drugs are now included in this high-risk group. 14 Pregnant women with listeriosis may have only mild symptoms of the infection. However, they are at increased risk of having a spontaneous abortion during the first trimester or of giving birth to a premature infant with acute sepsis if they are exposed later in the pregnancy.…”

Tuberculosis reactivation during immunosuppressive therapy in rheumatic diseases: diagnostic and therapeutic strategies

“…In patients with latent tuberculosis infection (LTBI), inhibition of TNFa by monoclonal antibodies may result in dissolution of well formed granulomas and the release of viable mycobacteria causing reactivation of disease. Clinical studies of TB occurring in patients receiving a monoclonal antibody, infliximab, reported a relatively short median time to onset of TB (12)(13)(14)(15)(16)(17)(18)(19)(20)(21) Purpose of review Biological agents used to treat rheumatologic conditions have made a significant impact on these difficult to treat autoimmune diseases. The tradeoff has been an increase in infections, and particularly tuberculosis with tumor necrosis factor blocker use.…”