Acute severe monarthritis: a rare manifestation of scrub typhus

Abstract

Scrub typhus caused by Orientia tsutsugamushi is an important cause for fever of unknown origin in endemic areas including India. The vasculitis associated with the disease leads to a variety of clinical manifestations. However, the joint involvement is quite rare and not reported in children. We present severe arthritis of hip joint associated with scrub typhus causing a diagnostic and management challenges in a 4-year-old girl.

Background

Scrub typhus caused by Orientia tsutsugamushi is prevalent in South and East Asia regions including India. The vasculitis and perivascular inflammatory changes associated with the disease lead to a wide range of clinical manifestations.^{1 2} However, the joint involvement is very rarely described with scrub typhus.^{3 4} We present severe arthritis of hip joint associated with the disease in a 4-year-old girl.

Case presentation

A 4-year-old female child from rural South India presented with a history of moderate-degree intermittent fever of 20-day duration. She also had abdominal distention for 10 days and vomiting for 2 days which were resolved at the time of admission. She had received oral amoxicillin for her illness from her previous physician. At admission, she was found to have severe pain in right hip joint and limping. She could not bear weight on the same side. Her birth and developmental history was unremarkable. On examination, her anthropometry revealed weight of 11 kg, height of 90 cm and weight/height ratio between −2 to −3 Z score. Her blood pressure was 100/54 mm Hg, pulse rate, 100/min and respiratory rate 20 breaths/min. She had tender right hip joint with severe restriction of movements. A careful search revealed 0.5 cm×0.5 cm eschar on the right shoulder. She also had hepatomegaly; 6 cm below right costal margin with a span of 11 cm. Examination of other systems was within normal limits.

Investigations

The lab investigations revealed total leucocyte count of 17 000/µL with lymphocytic predominance (62%) with haemoglobin of 11.9 g/dL, platelet count of 602×10³/µL, erythrocyte sedimentation rate (ESR) of 55 mm/hour and C reactive protein (CRP) of 13 mg/dL. Her liver function tests and renal function tests were normal. Antibodies to O. tsutsugamushi IgM ELISA and microimmunofluorescence IgM were positive. Blood culture, Widal test, standard agglutination test for brucella, IgM for dengue and leptospira and smear for malarial parasite were negative. Ultrasound of right hip showed mild joint effusion. The X-ray of pelvis and hip joints was normal.

Differential diagnosis

The common causes of fever of unknown origin in the region included enteric fever, scrub typhus and leptospira which were ruled out by relevant investigations. Brucellosis was suspected in view of prolonged fever and associated arthritis, but the tests for the same were negative in this case. A careful search for staphylococcal skin infection was negative. There was no history suggestive of urinary or genital infections in the recent past. The complete blood count and peripheral smear examination ruled out the possibility of acute lymphoblastic leukaemia which is a common malignancy in this age group.

Septic arthritis was the most difficult to rule out, but the clinical course, radiological findings and positive tests for scrub typhus played a determining role.

Treatment

Further, orthopaedic consultation was sought, they advised arthrotomy suspecting septic arthritis. However, considering her locality, long duration of illness, clinical findings and positive serological tests for scrub typhus, the possibility of reactive arthritis was entertained and we decided to monitor the child closely. Meanwhile, she was started on ibuprofen 10 mg/kg every eighth hourly, injection ceftriaxone 75 mg/kg/day in two divided doses and adequate hydration. She promptly responded to therapy, and her pain, tenderness, restriction movement, limp and hepatomegaly resolved by day 3 of initiation of therapy.

Outcome and follow-up

At the end of 1 week, repeat ultrasound of hip joint showed resolution of effusion. ESR and CRP were normalised. The child was discharged on oral medication on day 7 for three more days. At 1-month follow-up she remained asymptomatic and the right hip joint examination was normal. Her weight was increased by 400 g.

Discussion

Scrub typhus accounts for about 8% of acute fevers of unknown origin in endemic countries. The clinical manifestations vary widely in children from mild disease to severe life-threatening illness. The regional or generalised lymphadenopathy, hepatomegaly, splenomegaly, gastrointestinal symptoms and maculopapular rashes have been described in 23%–93%, 66%, 33%, 40% and 30%, respectively. Eschar at the site of mite bite though classical may not be always observed. The incidence of eschar ranges from 7% to 68%. Pneumonitis, encephalitis, acute kidney injury, myocarditis and septic shock are known complications of scrub typhus. However, reactive arthritis secondary scrub typhus has been very rarely reported in adults but not in paediatric population.^{2 3}

Indirect immunofluorescence assay detecting raising IgG titre or IgM titre >1:80 is the gold standard for the diagnosis of scrub typhus and the same has been recommended by WHO. Nested PCR and IgM ELISA for scrub typhus are also used for diagnosis. Doxycycline (4 mg/kg/day up to a maximum of 200 mg/day) and ceftriaxone for a minimum duration of 5 days or three afebrile days remains the standard of care. Chloramphenicol or azithromycin may be used alternatively.⁴

In the present case, a child belonging to the endemic area with long duration of fever, eschar and hepatomegaly remained undiagnosed for a long duration with multiple physician contacts. The high index of suspicion, clinical features along with hepatomegaly, positive IFA and IgM ELISA lead to a definitive diagnosis of scrub typhus. But severe monarthritis caused significant anxiety until the reports of definitive diagnostic tests arrived. A dilemma whether to consider early arthrotomy challenged the clinical decision. But prompt initiation of definitive treatment with close clinical monitoring prevented unnecessary invasive joint exploration. Presence of an extra-articular infection in the form of scrub typhus, mild joint effusions without hyper echogenicity on ultrasonography, extended discussion with surgical and radiology faculty, close monitoring and re-evaluation favoured the diagnosis of reactive arthritis.

Reactive arthritis is an autoimmune condition that develops in response to an extra-articular infection.^5–7 It is usually a sterile inflammatory arthritis manifesting within 1–3 weeks after a known infection. No satisfactory diagnostic criteria or classification are available for reactive arthritis. Although the arthritogenic infections usually confined to genital or gastrointestinal infections, the spectrum of infections varies widely.⁶ A single large joint in the lower extremities, such as the hip or knee joint, is involved most commonly. The plain X-rays of joints usually do not exhibit positive findings.^6,7 The ultrasonography of the joint may reveal minimal effusions. The hyperechoic or mixed aspects of the joint fluid suggesting septic origin are absent in reactive arthritis. Stool and urine culture, serology for arthritogenic bacteria or PCR to detect bacterial DNA from synovium may be needed for diagnosis. Treatment modalities include mainly non-steroidal anti-inflammatory drugs.^{1 5–7} Most cases of reactive arthritis remit after single episode.

Learning points.

• In endemic areas, it is necessary to consider scrub typhus as one of the differentials for any prolonged fevers with unknown cause.

• As in some infectious diseases, reactive arthritis remains a possible localisation with scrub typhus and can be confused with septic arthritis.

• Medico-surgical consultation based on careful analysis of clinical, biological and radiological data with close clinical monitoring can avoid unnecessary invasive interventions.