INFECTIONS IN SYSTEMIC LUPUS ERYTHEMATOSUS AND RHEUMATOID ARTHRITIS

https://doi.org/10.1016/S0891-5520(05)70149-5Get rights and content

Section snippets

INFECTIONS IN SYSTEMIC LUPUS ERYTHEMATOSUS

Patients with systemic lupus erythematosus (SLE) have a higher infection rate than the general population. It is estimated that at least 50% of them will suffer a severe infectious episode during the course of the disease. Its prevention and treatment is particularly relevant now that improvements in the control of the disease activity and of some complications, such as renal failure, have increased significantly the life expectancy of these patients.208

Infections may be related to the

PREDISPOSING FACTORS

Predisposing factors for infection in patients with SLE are diverse (Table 1). Defects in phagocytic cell function are particularly common in periods of disease activity and in untreated patients.6, 30, 111, 140, 146, 196, 282, 283, 286 Patients with SLE have cellular immunity impairments with lymphopenia, CD4 lymphocytopenia, decrease in the production of some cytokines,23, 258 and reduction in the production of immunoglobulins and in the complement levels.60, 138, 162, 179

The elimination of

SYNDROMIC APPROACH

Patients with SLE may have local or systemic infections. The former are usually related to the decrease in the local defense mechanisms caused by the disease, renal failure, or invasive diagnostic or therapeutic procedures. Disseminated infections reflect the immunologic deficiency caused by therapy, particularly by corticosteroids.

Considering the characteristics of these patients, most common infections involve the skin, the lower respiratory tract, the urinary tract, the central nervous

VIRAL INFECTIONS IN SYSTEMIC LUPUS ERYTHEMATOSUS

For most viral infections it can be said that there is no unquestionable evidence of a higher infection rate in patients with SLE. Furthermore, it cannot be said that these infections behave more aggressively, or show more resistance to therapy or more propensity toward chronicity. Most publications include very few cases. The potential role of some viruses as inducers of SLE flares never has been proven in our opinion. The authors will discuss some viruses that deserve special attention.

VARICELLA-ZOSTER VIRUS

The varicella-zoster virus (VZV) shows a higher infection rate in patients with SLE, but disseminated or very aggressive episodes are exceptional.118 In Kahl's work, disseminated infections accounted for 11% of episodes, but this experience is not confirmed by other authors.135 Moga et al181 followed 145 SLE patients for a mean period of 7.6 years. They detected 20 VZV infections in 19 patients (13.1%) with no disseminated episode among them. Incidence was higher among patients treated with

CYTOMEGALOVIRUS

Undoubtedly, cytomegalovirus (CMV) may be a cause of severe infection in patients with SLE, but it occurred only twice in the series of fatal infections in SLE published by Hellmann et al.118

Some authors describe the ability of CMV to induce the increased expression of some autoantigens that are classically present in patients with SLE,116, 219, 241, 284, 285 but there is not enough evidence to sustain this relationship.

A longitudinal study failed to detect any relationship between CMV viruria

EPSTEIN-BARR VIRUS

Except for anecdotal cases, no clear evidence has established a relationship between Epstein-Barr virus (EBV) infection and SLE.24, 177, 257 Some SLE patients have high antibody titers against different EBV antigens,145, 170, 235, 253, 269, 281 and patients with SLE produce antibodies against Epstein-Barr nuclear antigen (EBNA) peptide and against SmD.92, 115 These suggest that molecular mimicry may play a role in the induction of anti-SmD autoantibodies.230

It never has been demonstrated that

PARVOVIRUS B19

Human parvovirus B19 may produce clinical syndromes characterized by fever, thrombocytopenia, leukopenia, and anemia together with the production of antinuclear antibodies. Consequently, it may be difficult to distinguish from SLE or juvenile rheumatoid arthritis (RA) and always must be excluded in patients who present with articular symptomatology and fever.101, 136, 171 In a series of 7 children from 6 to 15 years of age infected by human parvovirus B19, 6 presented with butterfly wings rash

OTHER VIRUSES

The association of SLE and human immunodeficiency virus (HIV) is rare and is mostly serendipitous. However, it has been reported that this coinfection resulted in the improvement of the clinical manifestations of SLE and the elimination of the autoantibodies.13, 54, 86 It is important to remember that HIV enzyme-linked immunosorbent assay (ELISA) may show false positives in patients with SLE.17

There is no solid association between SLE and other retroviruses, and no evidence suggests a higher

BACTERIAL INFECTIONS

Bacterial pathogens cause more than 90% of the infectious episodes in SLE patients in some series.118, 143, 197, 208, 209, 225 Common bacteria, such as Staphylococcus aureus, Enterobacteriaceae, and nonfermentative gram-negatives, predominate. In a series of 544 patients with SLE, gram-negative sepsis was among the most common causes of severe infection in this population.143 The authors will review some microorganisms with a high incidence or a peculiar behavior in this group of patients.

OTHER BACTERIAL INFECTIONS

Infections caused by Yersinia spp., Neisseria meningitidis, Campylobacter spp., Pasteurella multocida, Rhodococcus spp., Pseudomonas spp. or Tropheryma whippelii, among others, have been reported in the literature regarding SLE patients. Sometimes, the single peculiarity of the cases is the severity of the infection or the tendency toward recurrence in some cases.14, 33, 39, 75, 82, 133, 158, 173

There is no clear evidence of a special susceptibility of SLE patients to suffer infections caused

TUBERCULOSIS AND OTHER MYCOBACTERIAL INFECTIONS

Tuberculosis should be considered and excluded in all SLE patients, especially in those treated with corticosteroids, living in endemic areas, or with a suggestive history or positive tuberculin skin test (PPD).242

In a series of 311 SLE patients followed up from 1963 to 1979, there were 16 cases of tuberculosis, accounting for the very high incidence of 5000 per 100,000 population. A high proportion of the patients had severe extrapulmonary or miliary disease. Once again, the initial symptoms

SYSTEMIC MYCOSIS AND THE PATIENT WITH SLE

Pneumocystis carinii caused 3 of 24 lethal infections in the classical SLE series by Hellman et al.118 The clinical picture is distinctively different from HIV patients. It has a rapidly progressive course with a short prodromal period.

Although P. carinii pneumonia may take place in untreated SLE patients, this should be considered the exception that confirms the rule.95, 214 In a series of six SLE patients with P. carinii pneumonia, all were on high doses of corticosteroids and developed the

PARASITIC INFECTIONS

Systemic parasitic infections are rarely described in patients with SLE and mostly consist of case reports. In the literature of the last 20 years, we draw attention to some cases of paragonimiasis,150 toxoplasmosis in different locations,20, 66, 67 disseminated strongyloidiasis,237, 272 visceral leishmaniasis,79 and Acanthamoeba meningitis.107 It is important to differentiate the symptoms caused by these complications from those of a period of disease activity.

FEVER OF UNKNOWN ORIGIN IN SLE

One of the most crucial problems of febrile SLE patients is to distinguish if fever is caused by the activity of the disease or by an infection. First of all, it must be said that both situations may coexist. The detection of an evident focal lesion, a high count of white blood cells (WBC), the presence of chills, or the isolation of a pathogenic microorganism from a significant sample tend to indicate infection. However, no laboratory test is so definite as to be useful in a concrete clinical

VACCINATION AND PROPHYLAXIS IN SLE PATIENTS

The first point of interest regarding the use of vaccines in patients with SLE is its safety. Some reports of lupic flares after vaccination or of increased autoantibody levels raise the issue. However, studies with the pneumococcal and influenza vaccine did not prove any increase in the incidence of adverse effects or reactivation episodes.88, 147, 220, 279 With other vaccines, particularly those that use live virus, safety limits remain to be determined. The safety of hepatitis B vaccine is

INFECTIONS IN RHEUMATOID ARTHRITIS

Rheumatoid arthritis (RA) is a chronic autoimmune disease, with unknown etiology, that affects more than 4 million people in the world. The chronic inflammation may produce the destruction of the bones and joints and permanent deformities. Attempts to implicate an infective agent in the pathogenesis of RA (Parvovirus B19, Epstein-Barr virus, Mycobacterium tuberculosis) have only provided circumstantial evidence.91, 124

It has not been established whether RA implies an increase in the rate of

IMMUNOSUPPRESSION-RELATED INFECTIONS

The immunosuppression of the patient with RA is mainly pharmacologic.12, 21, 49, 76, 228 The prolonged use of antiinflammatory drugs may lead to parallel masking of the signs and symptoms of the infection. Most commonly used drugs are corticosteroids, nonsteroidal antiinflammatory drugs, methotrexate, hydroxychloroquine, leflunomide, cyclosporine, and the new α-TNF inhibitors (infliximab and etanercept).

The adverse effects of the use of corticosteroids, cyclosporine, and cyclophosphamide are

VIRAL INFECTIONS IN RA

Patients with RA may suffer all kinds of viral infections, although there is no evidence to support that the disease or the activity periods are caused by any virus.9, 12, 28, 64, 76, 83, 155, 226, 250

VZV infection is the most common viral complication among patients with RA, particularly among those receiving high doses of methotrexate. Extension is usually confined to a metamera and rarely disseminates. Considering the age and underlying condition of the patients, antiviral therapy is

BACTERIAL INFECTIONS

There is no evidence that support any etiologic role of bacterial infections in the origin of RA. Patients with RA may suffer diverse bacterial infections, but patients with septic arthritis are the only ones specifically related to this underlying condition and the authors will review them in detail. The remaining bacterial infections behave as in other population groups and the authors will only mention some relevant details.65, 117, 125, 132, 151, 160, 227, 252, 270

Neither tuberculosis nor

FUNGAL INFECTIONS IN RA

Fungal infection in RA patients is promoted by methotrexate and corticosteroids.26, 83, 155, 160, 207, 226, 228, 248 Two thirds of the described cases presented in periods of intense lymphopenia (related to the RA itself or to the use of steroids or methotrexate). It usually has an abrupt onset with high fever, dry cough, and severe respiratory failure. Chest radiograph may show an interstitial focal or diffuse pattern that may be confused with methotrexate pneumonitis.115, 231 Differential

PARASITIC INFECTIONS

There is no evidence of a particular relationship between RA and parasitic diseases. There are some reports describing, for example, Strongyloides stercoralis infection57 or the reactivation of cutaneous leishmaniasis.266

MISCELLANEOUS

Patients with RA may have fever caused by the progression of the disease, although on most occasions it does not fulfill the criteria of fever of unknown origin. When this happens, an infectious etiology has to be excluded before assigning it to the underlying condition.44, 265

Respiratory tract infections are among the most common in this group of patients and may have substantial morbidity and mortality. It is important to remember that these patients should receive the influenza vaccine every

SEPTIC ARTHRITIS

Since 1958 it has been known that joint infections are more common in patients with RA than in the general population.50, 96, 121, 141, 265 There are many reasons for this situation including the deficit in vascular flow of the joints, deficient polymorphonuclear phagocytosis in the damaged joint, the absence of C3 receptors on the cellular surface, and the increased bacterial inflow into the joint caused by the rupture of the hematoarticular barrier.34, 186 Septic arthritis is characteristic

First page preview

First page preview
Click to open first page preview

References (288)

  • Fernández GuerreroM.L. et al.

    Visceral leishmaniasis in immunocompromised hosts

    Am J Med

    (1987)
  • D. Fishman et al.

    Splenic involvement in rheumatic diseases

    Semin Arthritis Rheum

    (1997)
  • J.D. Fortenberry et al.

    Fatal Pneumocystis carinii in an adolescent with systemic lupus erythematosus

    J Adolesc Health Care

    (1989)
  • G.C. Gardner et al.

    Pyarthrosis in patients with rheumatoid arthritis: A report of 13 cases and a review of the literature from the past 40 years

    Am J Med

    (1990)
  • L. Georgescu et al.

    Lymphoma in patients with rheumatoid arthritis: Association with the disease state or methotrexate treatment

    Semin Arthritis Rheum

    (1997)
  • S. Abramson et al.

    Salmonella bacteremia in systemic lupus erythematosus: Eight-year experience at a municipal hospital

    Arthritis Rheum

    (1985)
  • J. Abruzzo

    Rheumatoid arthritis and mortality

    Arthritis Rheum

    (1982)
  • Abu ShakraM. et al.

    Hepatitis B and C viruses serology in patients with SLE

    Lupus

    (1997)
  • A. Addisu

    Rheumatoid arthritis as a primary manifestation of human immunodeficiency virus (HIV) infection

    Ethiop Med J

    (1994)
  • D.A. Ainscow et al.

    The risk of haematogenous infection in total joint replacements

    J Bone Joint Surg [Br]

    (1984)
  • H. Al-Hadithy et al.

    Neutrophil function in systemic lupus erythematosus and other collagen diseases

    Ann Rheum Dis

    (1982)
  • M. Altz-Smith et al.

    Cryptococcosis associated with low-dose methotrexate for arthritis

    Am J Med

    (1984)
  • F.G. Andersen et al.

    Systemic lupus erythematosus associated with fatal pulmonary coccidioidomycosis

    Tex Rep Biol Med

    (1968)
  • D. Anderson et al.

    Herpes zoster infection in a patient on methotrexate given prednisone to prevent postherpetic neuralgia

    Ann Intern Med

    (1987)
  • Balbir GurmanA. et al.

    Primary subcutaneous nocardial infection in a SLE patient

    Lupus

    (1999)
  • H. Balfour

    Varicella-zoster virus infection in immunocompromised hosts

    Am J Med

    (1988)
  • P. Bambery et al.

    Blood transfusion related HBV and HIV infection in a patient with SLE

    Lupus

    (1993)
  • J. Barrier et al.

    [Gougerot-Sjögren's syndrome. Clinical and biological correlations with the serology of Yersinia infections]

    Presse Med

    (1984)
  • W.J. Barson

    Granuloma and pseudogranuloma of the skin caused by Microsporum canis: Successful management with local injections of miconazole

    Arch Dermatol

    (1985)
  • W. Barth et al.

    Septic arthritis caused by Pasteurella multocida complicating rheumatoid arthritis

    Arthritis Rheum

    (1968)
  • H.E. Bateman et al.

    Remission of juvenile rheumatoid arthritis after infection with parvovirus B19

    J Rheumatol

    (1999)
  • J. Baum

    Infection in rheumatoid arthritis

    Arthritis Rheum

    (1971)
  • Y. Baykal et al.

    Toxoplasma infection in patients with systemic lupus erythematosus [letter]

    J Rheumatol

    (1998)
  • B. Beaman et al.

    Nocardia: Host-parasite relationships

    Clin Microbiol Rev

    (1994)
  • BendiksenS. et al.

    A longitudinal study of human cytomegalovirus serology and viruria fails to detect active viral infection in 20 systemic lupus erythematosus patients

    Lupus

    (2000)
  • B. Bermas et al.

    T-helper-cell dysfunction in systemic lupus erythematosus (SLE): Relation to disease activity

    J Clin Immunol

    (1994)
  • R. Bhimma et al.

    Epstein-Barr virus-induced systemic lupus erythematosus

    South Afr Med J

    (1995)
  • F. Blanco et al.

    Survival analysis of 306 European Spanish patients with systemic lupus erythematosus

    Lupus

    (1998)
  • BonafedeR.P. et al.

    Hepatitis B virus infection and liver function in patients with systemic lupus erythematosus

    J Rheumatol

    (1986)
  • M. Bonneville et al.

    Epstein-Barr virus and rheumatoid arthritis [editorial]

    Rev Rhum Engl Ed

    (1998)
  • D.G. Borenstein et al.

    Haemophilus influenzae septic arthritis in adults: A report of four cases and a review of the literature

    Medicine (Baltimore)

    (1986)
  • J. Bradley et al.

    Infectious complications of cyclophosphamide treatment for vasculitis

    Arthritis Rheum

    (1989)
  • R.D. Brandstetter et al.

    Neisseria meningitidis serogroup W 135 disease in adults

    JAMA

    (1981)
  • F.C. Breedveld et al.

    Phagocytosis and intracellular killing of Staphylococcus aureus by polymorphonuclear cells from synovial fluid of patients with rheumatoid arthritis

    Arthritis Rheum

    (1986)
  • R. Brodman et al.

    Influenzal vaccine response in systemic lupus erythematosus

    Ann Intern Med

    (1978)
  • S. Broy et al.

    The role of arthroscopy in the diagnosis and management of the septic joint

    Clin Rheum Dis

    (1986)
  • M. Burgoyne et al.

    Chronic syphilitic polyarthritis mimicking systemic lupus erythematosus/rheumatoid arthritis as the initial presentation of human immunodeficiency virus infection

    J Rheumatol

    (1992)
  • L.H. Calabrese et al.

    Rheumatoid arthritis complicated by infection with the human immunodeficiency virus and the development of Sjögren's syndrome

    Arthritis Rheum

    (1989)
  • L. Caldeira et al.

    Fatal Pasteurella multocida infection in a systemic lupus erythematosus patient [letter]

    Infection

    (1993)
  • D. Campen et al.

    Candida septic arthritis in rheumatoid arthritis

    J Rheumatol

    (1990)
  • Cited by (104)

    • Z-form extracellular DNA is a structural component of the bacterial biofilm matrix

      2021, Cell
      Citation Excerpt :

      Z-DNA is more antigenic than B-DNA (Möller et al., 1982; Rich and Zhang, 2003), and antibodies specific to Z-DNA are more abundant in autoimmune diseases, in particular SLE (Rich and Zhang, 2003) and rheumatoid arthritis (RA) (Sibley et al., 1984). Individuals with SLE or RA also have a higher prevalence of bacterial infections (Bouza et al., 2001). This clinical outcome may be the result of host-derived Z-DNA-binding proteins, or the induction of Z-DNA-specific antibodies during the course of these chronic diseases that inadvertently stabilizes the bacterial biofilm EPS.

    • Bacterial infections in the lungs of patients with systemic autoimmune diseases

      2020, Handbook of Systemic Autoimmune Diseases
      Citation Excerpt :

      The treatment with systemic GCs interferes with phagocyte function; decreases the number of macrophages, dendritic cells, and circulating B and T cells; and inhibits transcription of nuclear factors (as NF-κB). These anti-inflammatory and immunosuppressive effects result in an increased susceptibility to pneumonia caused by Legionella pneumophila and Nocardia [8,10,12,20,24,25]. There is a dose-related relationship between the use of prednisone and the risk of pneumonia [10,26].

    View all citing articles on Scopus

    Address reprint requests to Emilio Bouza, MD, PhD Servicio de Microbiología y Enfermedades Infecciosas-VIH Hospital General Universitario Gregorio Marañón Dr. Esquerdo 46 28007 Madrid Spain e-mail: [email protected]

    *

    Clinical Microbiology and Infectious Disease Service, Hospital General Universitario Gregorio Marañón, University of Madrid, Madrid, Spain

    View full text