Clinico-epidemiological profile of reactive arthritis patients attending tertiary care center of Eastern India

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Reactive arthritis (ReA) is a conglomeration of articular, entheseal, mucocutaneous, and ocular manifestations resulting from an autoimmune response to gastrointestinal (GI) infections with Shigella, Salmonella, Campylobacter, and other organisms, as well as genitourinary (GU) infections (especially with Chlamydia trachomatis).¹ The diagnosis of ReA is mostly clinical because of the unavailability of definitive diagnostic tests or validated criteria.² The Indian published data on ReA primarily comes from rheumatology, with a paucity of data from dermatology.

This retrospective study evaluated 64 ReA patients treated in the Dermatology department from January 2019 to January 2023, following approval from the Institute Ethical Committee. Patient history, demographic data, mucocutaneous manifestations, joint involvement, associated systemic manifestations, laboratory parameters [complete blood count, liver function tests, renal function tests, viral markers (HIV, HBsAg, HCV)] and treatment received were extracted from the in-patient files. Diagnosis of ReA was made based on the presence of: (1) arthritis (asymmetric, mono, or oligoarthritis), (2) muco-cutaneous manifestations, (3) preceding history of enteritis (diarrhoea for at least 1-3 days to 6 weeks before the onset of arthritis) or urethritis (dysuria or discharge for at least 1-3 days to 6 weeks before the onset of arthritis), (4) positive HLA B27, (5) elevated erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP). Urine cultures were performed in all, potassium hydroxide microscopy and wet mount in patients with active urethral discharge, and X-ray of the involved joints were taken. Nucleic acid amplification test (NAAT) and polymerase chain reaction (PCR) could not be performed due to the lack of facilities.

Patients with active urethral discharge received doxycycline 100 mg twice a day for 3 weeks. Various treatments offered for ReA included biologics (injection infliximab, etanercept, and secukinumab), dexamethasone methotrexate pulse (DMP), oral indomethacin/tramadol, oral methotrexate, and sulfasalazine. Those willing to take injectables received either DMP or biologics, based on affordability. For DMP, patients received 100 mg of dexamethasone intravenously for 3 consecutive days at a 28-day interval, along with weekly methotrexate (15–20 mg) and daily sulfasalazine. Infliximab injection was administered as a 200 mg IV infusion at 0, 2, and 6 weeks, followed by a maintenance dose every 8 weeks. Secukinumab was given as a 300 mg subcutaneous injection at weeks 0, 1, 2, 3, 4, then every 4 weeks. Etanercept was administered as a 50 mg subcutaneous injection twice weekly for 3 months, then 50 mg weekly. All patients on biologics also received weekly methotrexate (10–20 mg), except one patient who was HbsAg positive. The Visual Analogue Scale (VAS) was used to assess improvement in joint pain and skin lesions. Score zero represented no improvement (at baseline), whereas score 10 was taken as a complete improvement for both joint pain and skin lesions.

Statistical analysis was performed using SPSS version 22 software. Frequencies and percentages were used for categorical variables, while mean and standard deviation were used for numerical variables. Treatment duration was modelled to calculate the mean VAS score improvement in joint pain and skin lesions for both treatment groups (DMP vs. infliximab). The treatment duration-weighted mean VAS scores between the two groups were compared using an unpaired “t” test.

Out of a total of 2127 admitted patients, 64 (3.01%) had ReA. The socio-demographic details are given in Table 1. Muco-cutaneous lesions preceded joint involvement in 11 cases (17.1%), while 14 cases (21.8%) had simultaneous involvement, while in 39 cases (60.9%), joint pain occurred first. The primary skin lesions were either papules (53-82.8% cases) or pustules (21-32.8% cases) [Figures 1a,1b and 2a, 2b]. Both types of lesions evolved into crusted papules with a peripheral collarette of scales [Figures 1a and 1b], which were subsequently shed, leaving residual hyper/hypopigmentation. Plaques formed by the coalescing of crusted papules had collarettes of scales [Figures 2a and 2b]. Other findings included annular plaques [Figure 3a-3c], keratoderma blenorrhagica, crusted plaques on the scalp [Figures 4a and 4b], circinate plaques in the axilla and inguinal areas [Figures 5a and 5b], circinate balanitis, and circinate vaginitis [Figures 6a and 6b]. Table 2 enumerates the muco-cutaneous manifestations. Sacroiliac joint was the most commonly involved joint, with 34 cases (53.12%) having some form of joint deformity [Table 3] [Figure 7]. Recurrent conjunctivitis was documented in 23 cases (35.9%). Renal and liver involvement were detected in 3 (4.6%) and 4 (6.2%) cases respectively.

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Figure 1a:

Multiple papules, crusted papules with collarette of scales.

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Figure 1b:

Crusted plaques with collarette of scale.

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Figure 2a:

Multiple pustules over the trunk.

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Figure 2b:

Crusted plaques with collarette of pustules.

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Figure 3a:

Multiple large annular plaques with crusted papules at margin in a female.

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Figure 3b:

Multiple large annular plaques with crusted papules at margin in a female.

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Figure 3c:

complete improvement of skin lesions post infliximab injection.

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Figure 4a:

Keratoderma blenorrhagica over soles.

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Figure 4b:

Crusted papules and plaques over scalp.

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Figure 5a:

Maceration and circinate plaques in axilla.

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Figure 5b:

Circinate plaques over inguinal area.

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Figure 6a:

Circinate balanitis.

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Figure 6b:

Circinate vaginitis.

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Figure 7a:

Patient with Contracture of right knee.

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Figure 7b:

Flexion deformity of toes with nail dystrophy and nail fold involvement.

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Figure 7c:

Deformity at metacarpophalangeal joint.

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All cases had elevated ESR and CRP, with mean values of 81.07 + 20.52 and 114.65 + 56.26, respectively. Two cases tested seropositive for HIV and one for HbsAg. Gram stain was negative for diplococci in all 27 cases with active urethral discharge, and 6 cases had >2 WBC per oil immersion field. KOH mount was negative and urine culture was sterile in all cases. Four cases had elevated liver transaminases. Elevated urea and creatinine, as well as high-grade proteinuria, were found in 3 and 2 cases, respectively. X-ray findings included reduced to absent joint space, juxta-articular osteopenia, enthesopathy, sacroiliitis, bony ankylosis, and periarticular erosions [Figures 8a-8d].

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Figure 8a:

X ray Pelvis shows subchondral sclerosis with articular margin irregularity in right sacroiliac joint suggestive of sacroiliitis.

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Figure 8b:

X ray of left hand shows reduced radio-carpal joint space with juxta-articular osteopenia at wrist joint, intercarpal joints, metacarpophalangeal joints and interphalangeal joints.

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Figure 8c:

X-ray of bilateral ankle joint shows plantar calcaneal spur (white arrows) and dorsal calcaneal spur at Achilles tendon insertion (black arrow) suggestive of enthesopathy.

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Figure 8d:

X ray of the pelvis shows irregularity of left ischial tuberosity with new bone proliferation suggestive of enthesopathy.

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Of 64 patients, 28 (43.7%) received dexamethasone methotrexate pulse (DMP), 32 (50%) received biologics, and 4 (6.2%) were on a combination of methotrexate (MTX) and sulfasalazine combination therapy. Infliximab was administered to 30 patients, one HbsAg-positive patient received a secukinumab injection, and one patient received an etanercept injection. The mean treatment duration for all patients, DMP group and infliximab group was 8.07 + 6.13 months, 3.67 + 2.16 months, and 12.95 + 5.57 months, respectively. The treatment duration-weighted mean VAS score improvement in joint pain was found to be significantly higher among patients receiving infliximab than patients receiving DMP [(8.14 +1.24) vs (2.56 +1.27); p-value = 0.000]. Similarly, the treatment duration-weighted mean VAS score improvement in skin lesions was found to be significantly higher among patients receiving infliximab than patients receiving DMP [9.01 +1.10) vs. 3.53 +1.60); p-value = 0.000]. Complete improvement in skin lesions and joint pain was observed in 19 (29.7%) and 4 (6.3%) patients, respectively, with injection infliximab [Figure 9a and 9b]. There was a complete improvement in nail dystrophy in five cases with infliximab injection [Figure 9c and 9d]. A significant improvement in joint pain and skin lesions was found with secukinumab but there was recurrence 6-weeks after treatment discontinuation. With etanercept also, significant improvement in skin lesions and joint pain was observed during a 4-month treatment period. There were no side effects to treatment with biologics. In the DMP group, two patients developed hyperglycaemia after three cycles and one patient complained of blurring of vision after 6 pulses.

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Figure 9a:

Pre-infliximab baseline picture of skin lesions loading dose.

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Figure 9b:

Complete improvement of skin lesions post-infliximab 8 weeks.

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Figure 9c:

Pre-infliximab baseline picture of nail dystrophy.

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Figure 9d:

Improvement in nail dystrophy post-infliximab 5 months post treatment.

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In the United States, the frequency of ReA ranges from 3.5 to 5 patients per 100,000, which is comparable to our study.³ Demographic and clinical profiles of patients were also similar to those in other studies [Table 4].^4-6 Methotrexate has been the most commonly used DMARD for treating chronic ReA, but has proved to be ineffective in clinical trials.⁷ Table 5 details the outcomes of biologicals in ReA. Pasricha was the first to try dexamethasone pulse therapy for ReA, with encouraging results. Kanwar et al. reported good results, including rapid relief of symptoms in 2 patients in their study.¹³ Dexamethasone pulse therapy is frequently practiced in India to treat reactive arthritis and can serve as a more affordable alternative for patients unable to afford biologics.

Our study is the first from India to examine a large number of patients with ReA, focusing on muco-cutaneous manifestations and highlighting “new findings” such as annular plaques, circinate plaques over flexures, and vaginal mucosa in a few cases. We have described the response of skin lesions and arthritis to various treatment modalities, with a focus on the anti-TNF α drug Infliximab.

The drawback of our study is that it is a retrospective study, including only admitted cases with severe disease. Additionally, we did not perform culture or Nucleic acid amplification test (NAAT) in all cases.