Disseminated Chronic Tophaceous Gout With Multi‐Tissue Involvement

ABSTRACT

Gout is a metabolic condition in which hyperuricaemia leads to deposition of monosodium urate (MSU) crystals in synovial and peri‐articular tissues. (1) Acutely, synovial deposition causes a painful inflammatory reaction. Over time, chronic hyperuricaemia can lead to deposition of uric acid crystals in alternate tissues, with granulomatous inflammatory responses forming gouty tophi. Chronic tophaceous gout affects approximately 3% of gout patients and presents as a spectrum from classical nodular tophi to rarer disseminated manifestations such as miliarial gout, panniculitis and ulcerative cutaneous gout. (2) This case details the management of a Maori patient in his 40s, presenting with acute infection of extruding gouty tophi across his lower limbs, managed with antibiotics, surgical debridement and oral urate‐lowering therapy. Multiple secondary complications of gout were identified during his care, including involvement of tendons and nerves in gouty deposits (with rare involvement of forearm extensor tendons), early onset polyarticular osteoarthritis with joint destruction and osteopenia. This case demonstrates the widespread effects of this disease and a range of complications secondary to poorly controlled tophaceous gout.

Key Clinical Message

Untreated and uncontrolled chronic tophaceous gout can lead to multiple complications. Disseminated Chronic Tophaceous Gout can involve multiple tissues including tendons, muscles, and nerves leading to significant morbidity and disability.

1. Introduction

Gout typically progresses over time from asymptomatic hyperuricaemia (serum uric acid > 0.36 mmol/L) to acute or recurrent gout, intercritical gout and ultimately chronic tophaceous gout [1, 2]. Acute gout flares classically present with joint pain and swelling provoked by the precipitation of MSU crystals into synovial spaces [3]. If untreated, this can lead to joint destruction and chronic arthropathy. Gout is the most common form of inflammatory arthritis, with an estimated prevalence of 2.9% in Australia and 6.06%–7.63% in New Zealand, for those of Maori and Pacific Islander ancestry [4, 5].

Approximately 3% of gout patients will develop chronic cutaneous manifestations [1]. Nodular tophi are the most common; formed by deposition of MSU crystals in the dermal and subcutaneous tissues, with granulomatous reactions leading to the formation of firm chalk‐like nodules, sharply demarcated from surrounding tissues [6]. Tophi are classically located in avascular tissues around the joints of the peripheral extremities, ears (helix), olecranon bursae, or flexor tendons (with the Achilles insertion point the most commonly involved tendon) [4]. Involvement of extensor tendons is extremely uncommon [7, 8].

The prevalence for disseminated gout has not been established, with current evidence limited to isolated case reports. Several uncommon forms of disseminated cutaneous gout have been described. These include miliarial gout, characterized by creamy milia‐like papules on an erythematous base and panniculitis, which demonstrates indurated, erythematous and irregular subcutaneous nodules or plaques. Ulcerative, bullous and pustular forms exist [1, 9, 10]. These aforementioned subtypes more often affect the extremities and skin distant from joints [11].

2. Case History

A male patient of Maori heritage in his 40s presented with rapidly worsening cellulitis of his right lower limb. The infection arose secondary to breaks in the skin caused by extruding tophi scattered across his posterior calf. He had a background medical history of class III obesity (BMI 55 kg/m²), smoking and tophaceous gout, diagnosed approximately 14 years prior.

Unfortunately, the patient's gout had been poorly controlled, with poor adherence to urate‐lowering therapy and limited lifestyle modification, including current smoking and high consumption of soft drinks containing high‐fructose corn syrup, with no significant dietary or weight modifications. This was due to social factors including financial stress, occupational demands, responsibilities as a single parent, and residing in a regional location with decreased access to specialist care. Despite being known to a rheumatology service for many years, his urate levels had remained persistently > 0.3 mmol/L (range 0.35–0.39 mmol/L), with escalating accumulation of tophaceous deposits throughout this time.

In this admission, the patient was noted to have numerous nodular tophi affecting his bilateral hands, wrists, olecranon, ankles, feet and metatarsals. He had disseminated cutaneous tophi, with non‐tender, firm, mobile chalky yellow nodules approximately 0.5–1 cm in diameter across his abdomen and both calves, present in Figure 1. Interestingly, there was no involvement of the ear or helix, which is commonly involved in tophaceous gout [4].

FIGURE 1.

Diffuse miliary and pannicular gouty tophi present across the abdomen. Lesions are hyperpigmented, indurated, and the majority contain small, firm, creamy, mobile nodules comprised of MSU crystals.

3. Investigations and Treatment

Extensive infected lower limb tophi demonstrated on his initial CT scan of his right leg (Figure 2). He was clinically unwell with sepsis and broad‐spectrum intravenous antibiotics were commenced on admission. In view of the clinical concern about infected collections, surgical debridement of the infected right lower limb deposits was performed to obtain source control. Intraoperative findings included extensive subcutaneous gouty deposits with full thickness involvement of skin down to fascia. The sural nerve and small saphenous nerve were encased in infected gouty deposits, requiring excision. A large tissue defect remained, extending across the right lower limb from the dorsolateral foot, over the lateral malleolus and posteriorly to approximately 10 cm distal to the popliteal crease (Figure 2B). A negative‐pressure dressing was applied and the patient progressed to split‐thickness skin grafting to cover this defect.

FIGURE 2.

(A) Commuted‐tomography image demonstrating widespread hyperdense monosodium urate crystal deposits present throughout the right lower limb prior to excision. (B) Large post‐operative tissue defect on the posterolateral right lower limb, requiring management with negative‐pressuring dressing and ultimately skin grafting.

Intra‐operative tissue samples demonstrated sodium urate crystals with mixed organism growth of Escherichia coli , Enterococcus faecalis (vancomycin and ampicillin resistant) and Pseudomonas aeruginosa . These multi‐resistant organisms reflect the patient's prolonged exposure to broad‐spectrum antibiotics prior to the procedure, with multiple courses of oral antibiotics prescribed previously in the community.

The patient's convalescence was further complicated by multiple acute polyarticular gout flares impacting on his rehabilitation program. Left wrist pain was investigated with ultrasound, demonstrating intra‐ and peri‐tendon thickening throughout the dorsal extensor compartment (greatest at extensor capri ulnaris) with scattered echogenic foci, consistent with gouty deposits [12]. X‐rays completed to evaluate for subacute joint pain demonstrated findings of severe osteoarthritic changes in the hands, wrists, knees, mid‐ and hind‐foot. Additional features of chronic gout‐related destructive change included juxta‐articular erosions with sclerotic joint destruction and subluxation, osteopenia and widespread calcified tophi. These radiographic features, and corresponding clinical images, are displayed in Figure 3.

FIGURE 3.

(A) Interphalangeal, metacarpophalangeal, and wrist joint destruction with corresponding radiological and clinical deformity and tophi. (B) Numerous calcified radio‐opaque tophi are present at the left olecranon. (C) Weight‐bearing x‐ray of both knees, demonstrating severe tricompartmental osteoarthritis with erosive sclerotic lesions.

Biochemical measures of inflammation were monitored, with C‐reactive protein falling from 264 mg/dL to 34 mg/dL following operative management; however, spiking to 184 mg/dL during acute gout flare of the left wrist. There was no evidence of impaired renal or liver function, diabetes mellitus, or hypertension. Anti‐cyclic citrullinated peptide, rheumatoid factor, and antinuclear antibody tests were negative.

Medical management was guided by the rheumatology team, with allopurinol utilized as urate‐lowering therapy and colchicine 500 mg daily as anti‐inflammatory prophylaxis of gout attacks. Allopurinol was up‐titrated by 100 mg monthly from 450 mg to 750 mg daily. A serum uric acid target of < 0.3 mmol/L was set in the setting of severe tophaceous disease, with the patient's serum uric acid falling from 0.39 mmol/L on presentation to 0.34 mmol/L throughout their 3 month admission [13]. Ongoing rheumatology follow up will be required to continue up‐titration of urate‐lowering medications. Analgesia was required, with short courses of non‐steroidal anti‐inflammatory medications utilized in acute flares and opiate analgesia in the immediate peri‐operative period.

4. Outcome and Follow Up

The patient experienced significant disability as a result of their disseminated disease, requiring prolonged inpatient medical and rehabilitation admissions. Healing of the large right lower limb wound was slow, in the setting of obesity and continued smoking. He is affected by chronic pain secondary to joint destruction and osteoarthritis, with limited mobility necessitating the use of a wheelchair. He is unable to return to work at present.

5. Discussion

This case demonstrates the myriads of complications that can arise from poorly‐controlled chronic tophaceous gout, as well as the clinical and radiographic appearance and distribution of rarer tophaceous deposits. Notably, atypical skin lesions, the involvement of muscles, nerves, and rare involvement of the extensor tendons of the forearm.

The cause of atypical tophi deposition is unknown, however is thought to be related to sustained hyperuricaemia [14]. Risk factors predisposing to the development of disseminated cutaneous gout include renal insufficiency, hypertension, chronic diuretic therapy (particularly in the context of renal or hepatic failure), long duration of disease, and lack of consistent use of urate‐lowering therapy [1, 11]. Individuals of Maori and Pacific Islander heritage have higher uricaemic acid concentrations compared to those of European ancestry [2].

Treatment requires lowering serum uric acids below their saturation point, with a more aggressive serum uric acid target of < 0.3 mmol/L, as opposed to the standard target of ≤ 0.36 mmol/L set in uncomplicated gout [13]. Slow regression of skin lesions are seen as the serum uric acid level falls and is maintained below this target [10, 11]. As such, surgical excision of gouty tophi is rarely performed, primarily offered to those with symptomatic tophi adversely affecting their quality of life due to pain and/or restriction of movement [15]. Unless the serum uric acid is appropriately suppressed, there is risk of ongoing accumulation of tophaceous deposits following surgical excision. Given failure of conservative management with antibiotics, with progression of infection and persistent pain, surgical management was deemed appropriate for this patient, despite persistent hyperuricaemia.

Chronic complications of poorly‐controlled gout contributed significantly to debility in this patient. Accelerated osteoarthritis, joint destruction with chronic deformity and multi‐tissue involvement contributed to chronic pain and impaired functional recovery, reinforcing the importance of achieving and maintaining serum uric acid suppression in cases of chronic tophaceous gout.

6. Conclusion

This case highlights a novel anatomical involvement, with gouty tophi affecting the extensor tendons greatest in extensor carpi ulnaris. Atypical gouty tophi can deposit in cutaneous and peri‐articular tissues, tendons, and nerves. These can cause significant debility including financial and physical impact to the patients leading to disability and loss of income, especially in the younger population. Pathophysiology of disseminated gouty tophi deposition in atypical locations remains unknown and future research is warranted to minimize the complications.

Author Contributions

Yee Leng Loh: conceptualization, visualization, data curation, methodology, investigation, validation, writing – review and editing, supervision, project administration, funding acquisition, resources. Fiona Combe: resources, investigation, writing – original draft, writing – review and editing, project administration, data curation.

Funding

The authors have nothing to report.

Ethics Statement

An exemption from ethical review was obtained from West Moreton Hospital and Health Service HREC.

Consent

Written informed consent was obtained from the patient for publication of this case report and accompanying images.

Conflicts of Interest

The authors declare no conflicts of interest.

Data Availability Statement

The data supporting the findings of this study are available from the corresponding author upon reasonable request. No publicly available datasets were generated or analyzed in this study.