Infections and Arthritis in Childhood

Fig. 21.1

Sweling around lateral malleolus of right ankle with MRI of the region and ulcreated positive Mantoux test. (a) The arrow shows swelling and erythema around the lateral malleolus. (b) Arrow shows ulcreated positive Mantoux test on the forearm. (c) MRI ankle showing osteolysis of the talus

It may sometimes be difficult to differentiate chronic infective arthritis from inflammatory synovitis. Soft tissue involvement is commonly seen in infective arthritis as seen in the index case where the tenosynovitis was present around the ankle. Imaging of the joint may reveal soft tissue collections.

Partially treated acute septic arthritis can also present as chronic synovitis of the joint and the inflammatory markers may be equivocal. History of typical inflammatory arthritis with early morning stiffness and improvement after mobility might be absent, and this suggests an alternative diagnosis such as septic arthritis. Previous history of fever and joint swelling and prior treatment with antibiotics can also provide a clue. Ultrasonography and MRI may be of help in differentiating this from an inflammatory pathology.

Postinfectious Arthritis

The incidence and prevalence of postinfectious arthritis are difficult to assess as they are heavily influenced by variations in the genetic factors and regional differences in infectious pathogens. Human immunodeficiency virus (HIV), for example, is far more common in Southern Africa and South Asia than in other parts of the world [11].

Infections with group A streptococci, which cause acute rheumatic fever and post-streptococcal arthritis, are more common in children from lower socioeconomic groups and communities in the developing world. It has been estimated that the global prevalence of severe group A streptococcal disease is at least 18.1 million cases, with 1.78 million new cases each year [12].

Arthritis has long been recognized as a major feature of infection with chikungunya virus. In fact, the name of the virus stems from the East African Makonde word for “that which bends up,” a reference to the stooped posture adopted by those who are infected. Large epidemics of this alpha virus have occurred in Africa and in Asia in recent times [13]. It is estimated that in the 2011 epidemic, 6.5 million people in South Asia were affected.

Case 3

A 12-year-old boy presents with pain and swelling of his ankles and knees. He had been having some trouble with walking, especially in the early morning, for a number of weeks, and he had had a similar episode a few years ago. He did not have fever or a skin rash and could not recall a recent upper respiratory tract infection. There was no history of recent trauma. He had recently been diagnosed with HIV infection after his mother was found to be HIV positive during an admission for pneumonia. On examination he is found to have generalized lymphadenopathy, anemia, and asymmetrical arthritis of small and large joints, with a total of 14 active joints. X-ray examination showed periarticular soft tissue swelling and osteopenia. His laboratory results revealed raised inflammatory markers, anemia, and a positive HIV ELISA. Investigations for TB including Mantoux, chest X-ray, and induced sputum all tested negative. He was diagnosed with HIV-associated arthritis and started on antiretroviral therapy, nonsteroidal anti-inflammatory drugs, and chloroquine. After a few days, his knees, wrists, and ankles were injected with corticosteroids with good effect.

Arthritis Associated with Viral Infections

HIV Arthritis

HIV arthritis can manifest in different ways depending on the stage of infection. Joint pain can also be a manifestation of treatment with antiretroviral agents.

Rheumatic manifestations have been described in 11–74 % of adult patients with HIV [14].

HIV has led to an increase in spondyloarthropathy in Africa, which was previously rarely seen as it is usually strongly associated with the HLAB27 gene, which is rare in Southern Africa [15]. Psoriasis is also more severe in HIV-positive adults and children [16]. Markedly painful polyarthritis has been described as part of the seroconversion syndrome in acute HIV infection. This is less common in children.

Most children with HIV arthritis present later in childhood, with previously undiagnosed infection. An arthritis similar to enthesitis-related arthritis may be seen in HIV infection. In one study, arthritis was the presenting feature of HIV in 78 % of patients in a cohort of children from a pediatric rheumatology clinic in Natal, South Africa [17]. Okong’o et al. reported 12 patients with HIV arthritis from Cape Town, of whom 9 had polyarthritis affecting small and large joints in the upper and lower limbs. The median age of onset was 9 years and 11 out of 12 were boys. In countries where HIV is endemic, HIV must be ruled out in any child who presents with arthritis.

Human Parvovirus B19

Also known as erythema infectiosum or fifth disease, this is usually a mild self-limiting infection characterized by fever, headache, arthralgia, coryza, sore throat, and a typical “slapped cheek” facial rash. The associated arthritis is usually symmetrical, affecting both small and large joints [18].

Chikungunya Virus

Severe symmetrical small and large joint polyarthritis follows shortly after the onset of fever. The arthritis can last from days to months and even years [19]. Chronic arthritis after chikungunya virus infection resembles rheumatoid arthritis in adults and can be very debilitating [20].

Other Virus Infections

Other virus infections known to present with arthritis include rubella; hepatitis A, B, and C; Epstein-Barr virus; mumps virus; adenovirus; coxsackievirus; HTLV-1; dengue; and varicella zoster virus. These viral infections usually cause self-limiting transient arthritis and are usually diagnosed based on their own distinct clinical features.

Reactive Arthritis

Case 4

An 11-year-old previously healthy boy residing in India presents to the hospital with acute, painful swelling of all proximal interphalangeal joints for the last 2 weeks. He had additive involvement of both ankles and knees. He also has painful skin lesions over his shins for the last 2 weeks. There was a history of an upper respiratory infection 4 weeks back for which the child had received some oral antibiotic for 5 days. On examination, he had several lesions of erythema nodosum over his shin and had symmetrical polyarthritis. His throat swab was suggestive of beta-hemolytic streptococcus, ASO titer was 1190 IU/ml, ESR 120 mm/h, and CRP 90 mg/L. His 2D echocardiography was normal and he did not have any feature suggestive of acute rheumatic fever. A diagnosis of post-streptococcal reactive arthritis was made. The patient was started on antibiotics and NSAIDs but did not improve much over 48 h. A short course of oral corticosteroids was given and resulted in dramatic resolution of signs and symptoms as well as resolution of acute-phase reactants. He was started on oral penicillin prophylaxis. His ASO titers repeated after 8 weeks were 400 IU/ml. Joint involvement resolved in 10 weeks and the child has since remained well.

Reactive arthritis in response to bacterial infections is much more common. Reactive arthritis is an acute arthritis usually presenting as asymmetrical oligo or polyarthritis after an infection. There is no evidence of a direct infection of the joint. The most common example of reactive arthritis is acute rheumatic fever (ARF). Post-streptococcal reactive arthritis is a separate clinical entity from ARF. Poncet’s disease is a form of reactive arthritis that occurs secondary to tuberculosis. Reiter’s syndrome caused due to enteric and urogenital infections is a triad of reactive arthritis, conjunctivitis, and urethritis.

Molecular mimicry with host protein is the likely mechanism of reactive arthritis in ARF. Many antigens expressed by the pathogens may have homology with the human proteins and can be identified as “self-antigens.” Pathogens causing gastrointestinal and genitourinary infections are more commonly implicated in reactive arthritis in adults. In children, Streptococcus and tuberculosis are more common causes of reactive arthritis.

By definition a “classic reactive arthritis” is characterized by a triad of inflammatory arthritis of large joints, urethritis/cervicitis, and uveitis or conjunctivitis. Table 21.1 gives the common pathogens causing reactive arthritis. In recent times the term reactive arthritis has evolved to include arthritis following other infections, such as group A streptococci and tuberculosis.

Table 21.1

Organisms associated with reactive arthritis

Enterobacteria:

Salmonella

Yersinia spp.

Campylobacter spp.

Shigella

Chlamydia:

Chlamydia trachomatis (more in sexually active persons)

Chlamydia pneumonia

Clostridium difficile

Mycoplasma

Mycobacteria:

Mycobacterium bovis

Mycobacterium tuberculosis

Streptococcus:

Acute rheumatic fever

Post-streptococcal reactive arthritis

Post-streptococcal Arthritis and Acute Rheumatic Fever (ARF)

Acute Rheumatic Fever

ARF occurs in susceptible individuals after infection with group A streptococci (GAS). ARF is characterized by involvement of the skin, brain, and heart in addition to the joints. The Jones criteria are helpful in diagnosis though they have been modified numerous times to improve performance characteristics (Table 21.2). The arthritis associated with ARF is usually transient and migratory. It initially involves the large joints of the lower limbs, extending to the upper limbs later in the course. Severe sequelae of the disease relate to the extent of the heart valve involvement.

Table 21.2

Jones criteria for the diagnosis of acute rheumatic fever

Supporting evidence of antecedent group A streptococcal infection

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