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Consequences of Neglecting Rheumatoid Arthritis Treatment: A Case of Arthritis Mutilans in an Older Woman
Abstract: Disease-modifying antirheumatic drugs (DMARDs) are a group of medications commonly used for the treatment of various rheumatologic disorders. Without DMARDs, inflammation can destroy joint tissues over the years to the point of deformity and instability, leading to arthritis mutilans (AM) in severe cases. This case report details an interesting case of AM, which is sufficiently uncommon that many physicians and geriatricians may be unfamiliar with it. Details of the case, AM presentation, and treatment are discussed. A brief review of DMARDs use in older adults is provided.
Key words: arthritis mutilans, geriatrics, DMARD, antirheumatic drugs
Arthritis mutilans (AM) is a rare and severe arthropathy typically associated with rheumatoid arthritis (RA) and psoriatic arthritis (PsA). AM generally affects the small joints of the hands and feet with severe erosive arthritis and bone lysis, which may lead to telescoping of digits. AM may also be associated with joint ankylosis. AM is seen in less than 5% of patients with PsA1 and in 4.4% of patients with seropositive RA.2 It is much less frequently associated with other forms of arthritis, such as juvenile chronic polyarthropathy, neuropathic arthropathy, mixed connective tissue disease, and diffuse scleroderma.
Disease-modifying antirheumatic drugs (DMARDs) are a group of medications commonly used in patients with inflammatory arthritis, ankylosing spondylitis, PsA, RA, and systemic lupus erythematosus. Gradually taking effect over weeks or months, DMARDs work by suppressing an overactive immune system, decreasing inflammation and joint damage, and preserving the structure and function of the joints, thus improving patients’ quality of life. The most commonly used DMARDs are methotrexate (MTX), sulfasalazine, hydroxychloroquine, and leflunomide. If patients do not adequately respond to these DMARDs, rheumatologists advise moving on to biologic DMARDs, which include medications such as adalimumab and etanercept. Without the use of DMARDs in patients with arthritis, inflammation can destroy joint tissues over the years to the point of deformity and instability, and, in severe cases, lead to AM.
This case report describes the case of an older woman who had been diagnosed with RA in midlife, then presented with a rare case of advanced AM to a clinic. Many physicians may be unfamiliar with AM. This article describes the disease presentation, diagnostic tests and screens performed, and prescribed treatment. A brief review of DMARDs use in older adults is also discussed with an emphasis on why early and continued treatment of RA and PsA is necessary in order to avoid irreversible joint damage.
Case Presentation
An 80-year-old woman presented with impaired functional status due to severe deformities in her hands and feet. The patient had home health aide services for assistance with activities of daily living, and she required assistance using her wheelchair.
She was first diagnosed with RA at age 35 years. At that time, she was treated with what was then the most advanced therapy, intramuscular gold injections, but her physicians discontinued this treatment when she was 40 years old due to inefficacy. She was lost to rheumatology follow-up until she was referred to the author’s rheumatology clinic at age 65 with advanced AM. Past medical history included osteoporosis, hypertension, and type 2 diabetes mellitus. Past surgical history (within the last 5 years) included: bilateral knee arthroplasty, bilateral hip arthroplasty, and right wrist stabilization surgery (unknown date of this last procedure). During her 70s, she had stopped taking a brief trial of hydroxychloroquine due to side effects of dizziness and insomnia; thereafter, treatment consisted of rare, as-needed courses of pain control with acetaminophen, a variety of nonsteroidal anti-inflammatory drugs in small doses, and tramadol. This treatment continues to present.
Upon examination, both hands had severe deformities in metacarpophalangeal joints (MCPs), proximal interphalangeal joints (PIPs) and distal interphalangeal joints (DIPs) including: shortening of the digits, flexion and subluxation of PIPs, DIPs, and MCPs. No edema or subcutaneous nodules were noted in hands or wrists. Range of motion in hands and wrists were limited. Surgical scar was noted on the right wrist. Additionally, subluxation of elbow, shoulder, and wrist joints noted bilaterally (Figure 1). Both feet were tender and not edematous. Stiffness and old surgical scars on dorsal aspects of first toes were noted bilaterally. There were surgical scars on plantar aspects of digits 1 through 4. Multiple toes appeared flexed in position. Ankylosis of tibiotalar joints as well as in all the joints of metatarsals and tarsal-metatarsals was observed. Subluxation of digital, interdigital phalangeal, and metatarsal joints was also observed (Figure 2). Hip joints’ flexion and extension were normal. Cervical spine was nontender; range of motion was limited in all directions due to pain. Lungs were clear to auscultation. A grade 2/6 systolic murmur was heard in the right second intercostal space.
The patient’s laboratory results are presented in Table 1.
Comprehensive metabolic profile was unremarkable. A complete blood count (CBC) showed white blood cell count was 5.59 x 103/µL (reference range: 4.8-10.8 x103/µL), hemoglobin was 10 g/dL (reference range: 12-16 g/dL), and platelet count was 151 x 103/µL (reference range: 130-400 x 103/µL).
X-ray of hands (Figure 3) showed subluxation of DIP and MCP joint spaces along with degenerative changes; fusion of multiple intercarpal joints; and flexion of interphalangeal joints were noted bilaterally (left > right). X-ray of feet (Figure 4) showed symmetric erosions of the distal metatarsal bones. Multiple toes were flexed bilaterally. These radiographic exams were consistent with AM.
Ultimately, the rheumatologists felt that the potential for benefit from aggressive treatment with DMARDs was minimal and considerably less than the potential for serious toxicity. The patient remains wheelchair bound and continues the same treatment noted above.
Discussion
AM, although rare, is the most destructive and erosive consequence of rheumatic disease with devastating effects on functional independence. This case shows the potential consequences of not treating rheumatism early and consistently in addition to the limited treatment and management options when AM is permitted to advance.
On clinical exam, AM is identified by hypermobile joints and shortened digits that can be elongated by traction-telescoping phenomenon. Radiologically, AM is characterized by acro-osteolysis, “pencil-in-cup” deformities, whittling, and ankylosis of interphalangeal joints.3 Larsen hand scoring system (0-110) and the mutilans hand scoring system (0-10) are radiologic tools to measure the severity of AM.4
Because active RA may lead to irreversible joint damage early in the disease process, as demonstrated, early diagnosis and treatment with DMARDs should not be delayed. In recent years, there has been a trend toward early and more dynamic treatment of RA using DMARDs in higher doses and in combination therapy to control the disease activity.5 When RA control is not achieved with commonly used DMARDs, therapy is then followed by biologic agents such as tumor necrosis factor inhibitors (TNFi). The patient was unable to explain why the RA had been allowed to progress so far due to cognitive issues. Calls were made to the patient’s family (daughters), but they also could not provide explanation regarding the patient’s RA.
In patients whose rheumatic symptoms have worsened despite medical therapy, or who have allowed their rheumatism to advance to AM, surgical treatment is an alternative consideration. Surgical treatment has shown some benefits in correcting various deformities of AM. The procedures range from arthroplasty to arthrodesis and aim to correct telescoping of joints by distraction lengthening and bone grafting. There are reported cases of arrest of osteolysis in AM after arthrodesis, suggesting that early surgical intervention may have a protective effect in preventing further joint resorption and shortening.6 Based on the surgical scars on the patient, noted in the physical exam, it seems surgery had been performed to stabilize the deformities caused by AM, but no medical record of the surgeries were found, and neither the patient nor the family members were able to verify why or when the surgeries were performed.
Despite many studies that point to efficacy and, in some cases, safety of DMARDs and biologics in treating RA in older individuals, there is still increased risk of toxicity associated with these agents. Therefore, many older adults are not adequately treated and suffer the physical and psychological effects of RA. But geriatric patients with rheumatic diseases should receive optimal treatment with DMARDs and biologics when possible. Clinicians should remember that the goals of treating arthritis in older adults are to achieve pain control, stop progression of the disease, and administer safe, tolerable treatments. A review of the use of DMARDs in older adults is below.
DMARDs in Older Adults
The same pharmacological therapies used in younger RA patients can sometimes be effectively and safely used in older patients. One study found that younger and older RA patients had similar results with MTX or MTX+TNFi. Across all age groups, improvement with use of MTX was similar with respect to assessment of physical function and X-ray progression. Likewise, TNFi+MTX had similar effects across all age groups, but the effects of the combination were more profound than in those only receiving MTX monotherapy.7 One study8 examined the safety of etanercept in older and younger patients with rheumatic diseases. The study measured serious adverse events, infectious events, medically important infections, and mortality in 597 geriatric patients (> 65 years) and 3296 nongeriatric patients with rheumatic diseases. It found no statistically significant difference in safety between older and younger adults.
Recent years have witnessed a rise in the use of DMARDs in geriatric patients with arthritis, but it seems that older adults are still often undertreated.Two American studies, the Consortium of Rheumatology Researchers of North America (CORRONA registry) and National Sample of Veterans with RA demonstrate these inequalities in treatment.9,10 In the CORRONA registry database of 9381 patients with RA, 2101 patients with disease onset after age 60 were matched with the same number of patients with disease onset between the ages 40 and 60 years.9 The primary outcome measures were the proportion of patients on MTX, multiple DMARDs, and biologics (etanercept, infliximab, adalimumab, and kineret) in each group.9 The use of MTX was slightly more common among older patients (63%) than among younger patients (59%).9 Older patients with RA often received MTX as a single agent and at much lower doses compared with younger patients.9,10 Older adults with RA were less frequently prescribed multiple DMARDs (30%) or biologic therapy (25%) compared with younger adults (40.5% and 33.1%, respectively).9 The other American study evaluated the trends in DMARD and biologic use from 1999 to 2009 in a national sample of 13,254 veterans with RA.10 MTX use as first-line agent increased from 39% to 57% over the study period. Patients aged 75 years and older were less likely to receive biologics than those younger than 45 years old.10 DMARD dose and prescription inequalities have also been noted in a European study conducted in Sweden with a sample of 592 RA patients.11 They reported that DMARDs were used in 100% of the younger patients (aged 30-55 years) as first-line treatment compared with 91.2% of the older patients (> 65 years). In contrast, glucocorticoids were used as first-line treatment in 68% of older vs 25% in younger patients.11
Those study findings may reflect physician concerns with DMARD- and biologic-associated toxicity in older adults with rheumatic disease and may be a barrier to prescribing. MTX is the most common DMARD used in treatment of rheumatologic disorders in all ages, and there are studies that point to increased prevalence of MTX toxicity in older adults including central nervous system toxicities, elevated liver enzymes, and pancytopenia.12-15 As MTX clearance decreases with decreasing creatinine clearance, dosing should be adjusted in older individuals or in those with renal impairment.16 On the other hand, studies from multiple MTX clinical trials have shown that age does not affect MTX efficacy or the rate of side effects. Renal impairment, however, does increase the risk of side effects.17 Overall, studies have shown that a low MTX dose (7.5 mg/week), along with monitoring of CBC and liver function, is a safe treatment course for older adults.18 Other commonly used DMARDs have relatively safe side effect profiles. Rise in hypertension is a major concern in using leflunomide in older patients with arthritis.19 Based on a few prospective studies on sulfasalazine, it was concluded that there are no age-related differences in toxicity or efficacy of this drug.20 Hydroxychloroquine is considered safe in older patients, however, there is concern over retinal damage. Thus, the American Academy of Ophthalmology recommends annually monitoring those prescribed the drug, 5 years after start of therapy.21
Older age and multiple comorbidities are also associated with a lower likelihood of receipt of anti-TNF therapy.22 A recent review on the use of anti-TNF in RA has confirmed that the benefit/risk balance barely declines with age.23 As mentioned earlier, the therapeutic effects of MTX+ anti-TNF combination is more profound than MTX alone. However, immunosuppression is a concern when using biologic agents. Adalimumab and infliximab have been demonstrated to increase tuberculosis (TB) risk, serious infection, and malignancy.24, 25 Similar side effect profiles have been reported with other anti-TNF agents.23 Studies have shown, though, that physician preference may play a more important role than the patients’ disease activity when choosing biologics over DMARDs.12
US Food and Drug Administration labels for biologic agents address safety regarding their use in older adults. The package inserts for infliximab, ustekinumab, and etanercept report no overall difference in safety in the geriatric population compared with younger age groups.26-28 However, these package inserts add that the risk of infection is higher in older individuals in general, thus caution should be used when administering these medications in the geriatric population. Given the side effect profile of biologics, pneumococcal and influenza vaccines should be given before initiation of treatment with any biologics. Screening for latent TB is also recommended for patients prescribed TNFi given the high risk of TB reactivation with these agents.
It is important for clinicians serving the geriatric population to understand the risks associated with systemic agents. Starting with small doses and then titrating up to higher doses to achieve an optimal therapeutic response is appropriate. Clinicians and patients must develop an individualized treatment plan, with assessment for side effects and measurements for benefits, and continue ongoing risk/benefit assessment.
Conclusion
This case report serves to educate readers on the rare but possible occurrence of AM and how it can be avoided with early diagnosis and treatment of rheumatic diseases. With the risk of irreversible joint damage, treatment with DMARDs for RA and other related diseases should not be delayed, but clinicians should be careful to consider each patient case individually, including factors such as comorbidities and quality-of-life goals, in order to minimize toxicity risk and potentially avoidable discomfort.
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