Does ultrasound detect joint and intestinal changes in psoriatic arthritis and ulcerative colitis after immunobiological treatment: A case report

Abstract

BACKGROUND

Ultrasound (US) can be a valuable tool for assessing arthritis associated with inflammatory bowel disease (IBD), especially in cases of psoriatic disease. The clinical case reviewed in this article addresses an exploratory finding that evaluates the effects of immunobiological treatments on dactylitis and IBD with the use of US techniques.

CASE SUMMARY

A 40-year-old Caucasian woman with psoriatic arthritis (PsA) and ulcerative colitis (UC) reported experiencing finger pain, knee arthritis, and bloody diarrhea. She showed a high Disease Activity index for PsA score and a severe Mayo score. She began treatment with adalimumab. Over the course of six months, the 18 MHz US procedure was performed on her joints and a 3.5 MHz US on her intestines. The joint US indicated dactylitis and swelling in her finger joints, while the intestinal US revealed 6.6 mm swelling in the sigmoid colon, increased abdominal fat, and high Doppler signal. Her fecal calprotectin level was 5984 mg/kg, and a colonoscopy showed that UC extended to the hepatic flexure, along with mild narrowing of the transverse colon. After six months treatment, all parameters showed improvement, including a remission of the Mayo score, better colonoscopy results, and Limberg score of 0.

CONCLUSION

More research is needed to find out the importance of using US in patients with PsA and UC as this could improve treatment strategies.

Key Words: Ultrasonography; Psoriatic arthritis; Ulcerative colitis; Tumor necrosis factor; Case report

Core Tip: This case study highlights a promising ultrasound (US) use in the simultaneous assessment of joint and intestinal inflammation in a patient diagnosed with psoriatic arthritis (PsA) and ulcerative colitis (UC). By employing high-frequency US (18 MHz) to evaluate dactylitis as well as abdominal US (3.5 MHz) to detect colonic inflammation, the findings underscore the versatility of this imaging technique. Following a six-month treatment regimen with adalimumab, significant improvements were observed in various clinical, laboratory, endoscopic, and sonographic parameters. These results suggest that US may represent a valuable tool for the integrated monitoring of PsA and UC and can potentially guide and enhance therapeutic strategies.

INTRODUCTION

Psoriasis (PsO) is associated with several manifestations, including joint involvement and systemic conditions such as uveitis and inflammatory bowel disease (IBD). Patients with PsO, psoriatic arthritis (PsA), and spondyloarthritis have a 1-4 times higher risk and a 1-6 times higher risk of developing IBD compared to the general population. IBD includes primarily two main forms: (1) Crohn's disease (CD); and (2) Ulcerative colitis (UC). Both CD and UC are chronic disorders characterized by intermittent remission phases and periods of active inflammation, with symptoms such as abdominal pain, diarrhea, and rectal bleeding. The risk of developing PsO, PsA, ankylosing spondylitis (AS), and IBD is polygenic and often these disorders overlap, which may explain the clustering of immune-mediated chronic inflammatory diseases with various phenotypes across generations[1]. IBD encompasses two conditions: (1) CD, which can affect any part of the gastrointestinal tract in a discontinuous manner and impact the intestinal wall transmurally; and (2) UC, which affects the mucosa continuum and concentrates primarily in the rectum[1-3]. Notably, the prevalence of IBD does not reflect the significant rates of subclinical intestinal involvement detected by endoscopic examinations or biopsies; actually, this condition rate can be as high as 65%-70%. A connection between joint manifestations and IBD may also be observed.

The pathophysiology underlying the hypothesis of "arthritogenic bowel" involves genetic factors. A significant cause is the high prevalence of the human leukocyte antigen (HLA)-B27 antigen, found in approximately 25% of individuals with spondyloarthritis and 78% of those with IBD. Other genetic factors, such as HLA-DRB1 and HLA-B44, have also been identified, along with non-histocompatibility factors like variations in the CARD15 gene, which increases the risk of sacroiliitis in CD[4,5]. These conditions are supported by transcriptomic analysis, which identifies CD 64+ myeloid cells as a source of interleukin (IL)-23 stimulation in the intestine. The situation is exacerbated by epigenetic alterations thought to occur due to microbial dysbiosis, triggering the transcription of several interleukins, including IL-17 and tumor necrosis factor (TNF). This process leads to the differentiation of Th17 Lymphocytes, mediated by autoreactive T and B lymphocytes. Consequently, locally recruited macrophages and lymphocytes that express intestinal markers, along with cytokines IL-17 and IL-23, can migrate through the intestinal vasculature. This movement is facilitated by increased vascular permeability associated with inflammation, allowing those cells to reach the synovial vessels. While substantial evidence supports such hypothesis, further research is necessary for its validation.[5,6].

Regarding AS, few reports detailing this disorder association with IBD are available. However, one study indicates a significant reduction in microbiota among AS patients, demonstrating dysbiosis similar to that seen in IBD patients, with a comparable bacterial profile. Nevertheless, stronger evidence is needed to provide more evidence for this association[7].

In recent years, high-resolution ultrasound (US), particularly Doppler technology in US, has proven beneficial in diagnosing and monitoring rheumatological diseases helping to evaluate synovitis and enthesopathies, especially in cases of subclinical disease activity. Advances in understanding intestinal imaging using US techniques have also allowed for the demonstration of pathological changes associated with IBD[8,9]. US can help characterize intestinal inflammation by highlighting hypoechogenicity and thickening of the inflamed intestinal wall, while Doppler assesses vascular changes due to intense neovascularization, inflammatory infiltration, small artery thrombosis, and dilation of arteries and veins that are manifestations of IBD[9,10].

CASE PRESENTATION

Chief complaints

This clinical case emphasizes the importance of US for assessing joint ill manifestations as well as detecting intestinal inflammation and helping monitoring treatments.

History of present illness

Two patients, 51 ± 11 years of age, were diagnosed with PsA and UC through colonoscopy. The intestinal US examinations performed revealed signs of inflammation while remaining blinded to their clinical conditions. One patient was female and the other was male. The female patient, a businesswoman, completed US treatment and follow-up, allowing her to be included in the study. In contrast, the male patient was excluded due to lack of follow-up on his intestinal US procedure.

History of past illness

The female patient had been diagnosed with PsO on her scalp and elbows eight years before.

Personal and family history

After experiencing skin lesions for four years, she began to develop inflammatory joint pain while opening and closing her fingers, along with arthritis in her left knee. Three years after these joint complaints started, she experienced over 20 episodes of bloody diarrhea and was subsequently diagnosed with UC. Her father had been diagnosed with PsA 20 years earlier.

Physical examination

Before starting the adalimumab treatment, the patient’s exams indicated she had: (1) Mild PsO according to the Psoriasis Area and Severity Index (PASI); (2) High score on the Disease Activity Index for PsA (DAPSA); and (3) Severe Mayo score (Table 1). The clinical evaluation was conducted using the PASI, which measures the severity of PsO based on four criteria: (1) Crythema; (2) Induration; (3) Scaling; and (4) The extent of the affected area. The severity of skin involvement is categorized based on the surface area affected (BSA) as follows: (1) No PsO (0 BSA); (2) Mild (< 10 BSA); (3) Moderate (10-20 BSA); and (4) Severe (> 20 BSA)[11].

Table 1 Clinical, ultrasound, laboratory, and colonoscopy parameters before and after treatment.

	Before	After
Psoriasis Area and Severity Index	8.3	2.0
Disease Activity Index for Psoriatic Arthritis	29.16	0
Mayo score	12	0
Paratenonitis	Present	Absent
Fecal calprotectin	5984 mg/kg	600 mg/kg
Colonoscopy	Intense inflammation	Remission
Intestinal wall thickness	6.6 mm	2.8 mm
Degree of thickening of perienteric fat	2	0
Doppler degree in the intestinal wall	3	0

To assess arthritis, the DAPSA score was used. This score includes the number of painful and swollen joints (28 in total), the patient’s visual analogue pain scale (ranging from 0 to 10), the physician’s assessment, and the inflammatory marker C-reactive protein. Disease activity is classified into four categories: (1) High (≥ 28); (2) Moderate (15-28); (3) Low (5-14); and (4) In remission (≤ 4)[12-14].

Laboratory examinations

The patient’s laboratory exams showed a negative rheumatoid factor, a fecal calprotectin level of 5984 mg/kg[15], serology testing for hepatitis B, C, human immunodeficiency virus, and syphilis, a negative Mantoux test, and no anomalies on the chest X-ray.

Imaging examinations

The patient gave her consent by signing the Informed Consent Form for the US evaluation and other procedures conducted at the Rheumatology Clinic. This evaluation was performed by a single rheumatologist with 17 years’ experience in general and articular US examinations, specifically for rheumatology and immune-mediated diseases, as part of the University's postgraduate program and the Hospital's US service. The assessment followed established protocols, using all appropriate equipment configurations for monitoring the treatment, and all images were recorded on an external hard drive. For the evaluation, the MyLab Gold 25 US system (Esaote SpA, São Paulo, Brazil) was used. It was equipped with an 18 MHz high-frequency linear probe for use in the joint assessment and a 3.5 MHz convex probe for intestinal examination. The Doppler specifications were standardized, featuring a frequency range of 2.5-8.0 MHz and pulse repetition frequencies of 0.7-1.0 kHz. The joints US assessment covered all the fingers, evaluating both dorsal and palmar recesses[9,16]. The intestinal US evaluation was conducted with the patient fasting and positioned supine to preserve the intestines' physiological state, minimizing interference from luminal contents and vascular changes. A comprehensive assessment of both the small intestine and colon was performed, scanning all segments in both the long and short axes, paying particular attention to any abnormal areas. The intestinal loops in the sigmoid colon region, including assessments of mesenteric fat thickening were specifically measured. Doppler signal evaluations were carried out to monitor the treatment parameters. Importantly, oral contrast was not used, as US allows dynamic, real-time observation of intestinal movements and caliber while the patient is at rest. The evaluation focused on the five concentric, compressible layers with varying echogenicities, assessing increased wall thickness greater than 3 mm, depending on the specific location. Additionally, the mesenteric fat and Doppler signal were graded from 0 to 3 to semi-quantify the severity of the inflammatory process[9,17].

MULTIDISCIPLINARY EXPERT CONSULTATION

When there is a link between arthritis and IBD, the concept of an arthritogenic bowel becomes particularly important. This connection emphasizes the need for a multidisciplinary approach, which is associated with better clinical outcomes. These outcomes include higher rates of sustained remission, reduced hospitalizations stay and reduced surgical procedures, as well as an overall improved quality of life as reported by patients. Additionally, a multidisciplinary approach encourages collaborative clinical decision-making, humanizes patient care, and enhances the integration of support, education, and research within specialized centers. Therefore, it is crucial to promote and incorporate multidisciplinary consultations as a standard practice for managing patients with UC, especially in complex clinical situations within tertiary care centers and IBD referral units[18,19].

FINAL DIAGNOSIS

The fingers’ joints examination revealed findings consistent with dactylitis, which was attributed to significant paratenonitis in the second and third proximal interphalangeal joints of the right hand, characterized by effusion. A bowel US showed 6.6 mm edema in the sigmoid colon wall and indicated grade 2 mesenteric fat and grade 3 Doppler signal on the Limberg scale. Additionally, a colonoscopy revealed severe UC extending to the hepatic flexure and mild stenosis of the transverse colon, with a Mayo score 3 and 7 UC Disease Activity Index Score.

TREATMENT

The treatment consisted of 100 mg adalimumab and azathioprine during six months.

OUTCOME AND FOLLOW-UP

All clinical, US, laboratory, and colonoscopy parameters showed improvement, indicating preserved mucosa with a distinct vascular pattern, with no edema, erosions, or ulcerations, and no signs of inflammatory activity (Table 1, Figures 1, 2 and 3).

Figure 1 Follow-up treatment after the use of adalimumab. A: It shows the presence of effusion as indicated by the color map in B-mode; B: It shows the absence of effusion (arrows). They illustrate the longitudinal dorsal recess of the second proximal interphalangeal joint with peritendinitis.

Figure 2 Monitoring intestinal inflammatory activity: Improvement after adalimumab treatment. A and B: Reduced intestinal wall thickening (arrows) and perienteric fat (star) (short axis images of the sigmoid colon); C and D: Decreased Doppler signal per the Limberg scale (arrows).

Figure 3 Treatment follow-up after adalimumab use. A: Colonoscopy show intense proctocolitis; B: Remission, respectively.

DISCUSSION

High-resolution B-mode and Doppler ultrasonography effectively translate clinical and often subclinical dactylitis into observable conditions such as synovitis, tenosynovitis, enthesitis, and inflammation of both the subcutaneous tissue and the periextensor tendon. Recently, a dactylitis score scale has been developed for patients with PsA, as this condition can be challenging to detect during clinical examinations. Patients frequently exhibit US abnormalities without accompanying inflammatory signs. The clinical significance of dactylitis is highlighted by its role as a marker of disease aggressiveness and poor prognosis in affected patients. An US study found that 35.7% of PsO patients exhibited subclinical dactylitis compared to a control group, along with a 30% occurrence of moderate peritendinitis of the fingers’ extensor tendon[18,20,21].

The use of US in UC has proven beneficial as it helps to identify structural damage to the large intestine a damage which is an indication of an active inflammatory process in the bowel. Accuracy of US in assessing the bowel inflammation extent and severity, as well as in monitoring therapeutic responses has been evidenced[19].

The TNF plays a crucial role in the pathogenesis of immune-mediated inflammatory diseases; hence, inhibiting TNF is vital for managing severe and progressive inflammatory conditions. This intervention can lead to rapid and sustained clinical remission, enhance quality of life, and prevent damage to other target organs. Adalimumab, the first fully human monoclonal antibody targeting TNF, has demonstrated efficacy and tolerability in patients with various extensive inflammatory diseases, including PsA, plaque PsO, and IBD such as CD and UC. Accurate mapping of intestinal manifestations in patients with PsA is crucial, as it allows for more precise treatment approaches. Adjustments in the therapeutic classes and the potential increase of the anti-TNF drug dosage may be necessary for effectively managing intestinal inflammation, since differences in dosing requirements compared to arthritis treatment exist. Research indicates that a higher dosage of adalimumab achieves sustained efficacy in inducing remission of intestinal inflammation, reporting a 25% success rate in moderate to severe cases over four years[22,23].

However, the limitations of US in UC affect its effectiveness in the assessments, as inflammation primarily affects the mucosa. The technique is better suited for identifying changes in deeper bowel layers, as seen in CD. Visualizing the rectum can be challenging, and mild or microscopic inflammation may not be detected, the tissues often appearing normal. In cases of remission, the bowel wall thickness typically returns to normal, further decreasing US sensitivity. Factors such as flatulence, obesity, and operator’s skill can also impact image quality. Therefore, while US may have some use, it cannot replace colonoscopy for confirming remission or for monitoring[19].

CONCLUSION

Our study emphasizes the importance of joint and intestinal mapping when treating patients with a humanized monoclonal anti-TNF agent. Further research is needed to determine the necessity of US monitoring in patients with PsA and IBD. This could improve the selection of safer and more appropriate treatment options for these patients.

ACKNOWLEDGEMENTS

We are grateful to the patients for their participation in this exploratory and innovative investigation of joint and bowel imaging.