Diseases mistaken for rheumatoid arthritis

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8 Diseases That Could Mimic Rheumatoid Arthritis — and Delay Your Diagnosis

Margaret Liang Harris was convinced that the pain in her joints was rheumatoid arthritis (RA). About six months after she had her first child, she got an ache in her elbow that was unlike anything she had experienced before; it felt like it was coming from deep inside her joint. And it was just as her own mother — who had been diagnosed with RA years back — had described her own pain.

“I went to my primary care doctor and told him my suspicions, but he didn’t believe me because I didn’t present with the ‘right’ signs,” she says. He drew her blood and tested it for everything else under the sun: blood sugar, cholesterol, liver and kidney function, and on and on — all of which came back normal. Liang Harris insisted that her blood be tested for rheumatoid arthritis, and eventually she got her RA diagnosis.

“My doctor was surprised,” she recalls. “I was not.”

Here’s the thing with rheumatoid arthritis: In early stages, it can be difficult to diagnose in some patients. Part of the reason is that RA can’t always be confirmed with just one test. And the more distinctive or obvious signs — such as deterioration or deformity in a joint — occur later once RA has progressed, explains Vinicius Domingues, MD, assistant professor of medicine at Florida State University and CreakyJoints medical advisor.

Rheumatoid arthritis is a type of inflammatory, autoimmune arthritis that typically causes joint pain, swelling, and stiffness in symmetrical joints throughout the body. Rheumatoid arthritis occurs when the immune system attacks the lining surrounding a joint,called the synovium. However, in some people RA can present less typically, which can make getting the right diagnosis tricky.

Rheumatoid Arthritis Blood Tests: Clearing Up Confusion

You may have heard about blood tests for certain antibodies helping to clinch a diagnosis of RA. But some blood tests used to help diagnose RA can be negative. Most people with RA are what’s known as seropositive — they have abnormally high levels of rheumatoid factor (RF) or anti-citrullinated peptides (anti-CPP) antibodies in their blood. These antibodies are produced by the immune system and play a role in the immune system attacking healthy joints and tissue.

But research shows up to half of people with RA are seronegative, which means they don’t have either of these antibodies in their blood.

“These patients may still have classic RA symptoms, such as joint pain and morning stiffness,” says Dr. Domingues. “But because this basic screen is negative, physicians may not refer the patient to a rheumatologist and instead start them on another treatment plan, when they should be taking RA medications.”

The Importance of Seeing a Rheumatologist

That’s why it’s important to see a rheumatologist if you think you might have arthritis symptoms, advises Elaine Husni, MD, MPH, vice chair of the department of rheumatic and immunologic diseases and director of the Arthritis Center at the Cleveland Clinic. A rheumatologist is a doctor who specializes in treating arthritis and certain autoimmune disease. They are trained to diagnose RA at an earlier stage, which may minimize unnecessary testing and treatment and help to improve overall patient outcomes.

That advice would have benefited CreakyJoints member Lindsey Stambaugh. Her symptoms also began after the birth of her son. Her first doctor told her the pain was psychological; a few years later, she was sent to a pain clinic, where she was given medications and injections to mute the symptoms. It wasn’t until Stambaugh started working in a rheumatologist’s office, who recognized symptoms during one of her flare-ups, that she was evaluated for and diagnosed with RA.

Conditions that Can Mimic RA

Another reason RA may be tough to diagnose in early stages is that some initial signs and symptoms can be difficult to distinguish from other conditions. Viral infections, other kinds of arthritis, and other autoimmune diseases may all be mistaken for RA, depending on which specific constellation of symptoms you have. It’s important to learn about these different diseases so you can be sure to be as specific as possible when describing your medical history to your doctor.

Some of the conditions that mimic rheumatoid arthritis include:

Psoriatic Arthritis

This form of inflammatory arthritis can be tough to distinguish from RA, particularly if there are no obvious symptoms of psoriasis, a different autoimmune disease that causes red patches of skin topped with silvery scales. Like RA, psoriatic arthritis can cause painful, swollen joints that are warm to the touch. However, psoriatic arthritis is more likely to also cause sausage-like swelling in the fingers and toes (called dactylitis), nail changes, foot pain (especially at the back of your heel or along the sole of your foot) which can signal enthesitis (or inflammation of soft tissue where it meets the bone), and lower back pain. Read more about psoriatic arthritis symptoms here.

Osteoarthritis

The main difference between OA and RA: RA is a systemic inflammatory condition; osteoarthritis (OA) is primarily a degenerative disorder where the cartilage that cushions the joints breaks down over time. OA is more likely to be confused with RA in a middle-aged or older patient when it involves small joints of the hands.

But some symptoms of OA and RA will differ. Swelling, for example, is hard and bony in OA and soft and warm in RA. Stiffness occurs in both conditions, but in RA, it’s worse in the morning or after resting the joint. In OA, a joint may get stiff after effort or overuse. (However, there is a form of OA called erosive or inflammatory OA, which affects joints in the hand and may also be confused for RA.) Blood tests and imaging studies can also help differentiate the two conditions.

Lupus

When lupus, a systemic autoimmune disease, affects the joints, it can cause symptoms similar to RA. Most people with lupus also experience flares, where symptoms get worse, then improve or disappear. Other similar signs of lupus and RA include fatigue, fever, and dry eyes. In some people with lupus, joint deformity may occur as well. The difference, however, is that it’s caused by loosening and lengthening of tendons and ligaments, not by joint erosion.

Some symptoms that are distinct to lupus include: a butterfly-shaped rash across the cheeks and nose, skin sensitivity to light, and Raynaud’s phenomenon, a condition where fingers and toes turn white or blue when exposed to cold or during stressful periods.

Viral Arthritis

Some viral infections — such as parvovirus B19 — can cause symptoms in multiple joints that may be mistaken for RA. In children, parvovirus may cause fever and rash on the cheeks, but usually not joint problems. Adults who’ve been in contact with children who have parvovirus, however, may develop joint soreness, typically in the hands, wrists, knees, and ankles. Joint symptoms from parvovirus usually clear up quickly, lasting only from a few days to several weeks.

Another virus that causes arthritis joint pain is called Chikungunya. It’s caused by bites from infected mosquitoes, is increasingly reported in travelers, and causes symptoms that closely mimic RA. Outbreaks have occurred in countries such as Italy, India, Indian Ocean islands, and those in the Caribbean. In some people, joint pain from Chikungunya can last for months. Doctors can use blood tests and exposure history to distinguish viral arthritis from RA.

Reactive Arthritis

Reactive arthritis is joint pain and swelling triggered by a bacterial infection in another part of your body — most often your intestines, genitals, or urinary tract. A number of bacteria can cause reactive arthritis; some are foodborne, such as salmonella and campylobacter, others are transmitted sexually, like chlamydia. Reactive arthritis usually targets your knees and the joints of your ankles and feet. The physical signs of both reactive arthritis and RA can be identical in the knees. Doctors usually diagnose reactive arthritis using history of infection, joint and muscle involvement, and imaging tests. Read more about reactive arthritis here.

Arthritis of IBD

People with inflammatory bowel disease (IBD) — including ulcerative colitis and Crohn’s disease — may develop peripheral arthritis that affects the knuckles and can be mistaken for RA. IBD-related arthritis can also cause symptoms in the elbows, wrists, knees, and ankles. Arthritis of IBD may be missed if symptoms of IBD — such as abdominal pain, diarrhea, or blood in the stool — aren’t prominent. Although no specific test can make a definitive diagnosis, X-rays and lab and blood tests can be used to rule out other causes of joint pain.

Lyme Disease

The most common tick-borne disease, Lyme disease can lead to bouts of severe joint pain and swelling, particularly in the knee. It can be confused with a number of conditions, including RA. That’s what happened to CreakyJoints member Rachel Drucker.

“I was misdiagnosed with Lyme’s disease by an infectious disease doctor, who prescribed me antibiotics,” she shared on Facebook. After three weeks on the meds with no pain relief, she sought the opinion of another doctor, who diagnosed her with RA.

Some signs that differentiate Lyme arthritis from rheumatoid arthritis: Pain can shift from one joint to another in Lyme disease, and Lyme arthritis rarely affects small joints in the hands and feet. Lyme is also often indicated by a rash in a bulls-eye pattern that expands slowly after several days. If you don’t have the characteristic rash, your medical history, a physical exam, and lab tests can help identify antibodies to the Lyme bacteria can help confirm or rule out the diagnosis.

Palindromic Rheumatism

Palindromic rheumatism is rare form of inflammatory arthritis. It’s characterized by sudden and recurrent attacks of painful swelling of one or more joints. Attacks may last for several days or just a few hours. Between attacks, palindromic rheumatism symptoms completely disappear and joints go back to normal, with no lasting damage, which can help distinguish it from RA. However, about a third of the people who have palindromic rheumatism will go on to develop RA, which does cause permanent joint damage.

How Rheumatologists Diagnose RA (and What You Can Do to Help)

Findings from a physical exam and medical history are important factors in diagnosing RA, say experts. Common RA symptoms include:

  • Joints that feel tender, warm, or swollen for six weeks or more
  • Multiple joints can be affected
  • Joint pain that is commonly symmetrical
  • Joint stiffness, especially first thing in the morning that lasts for an hour or more
  • Fatigue
  • Low-grade fever
  • Loss of appetite

While many of these symptoms can occur with other diseases, infections, or injuries, there are subtle traits unique to RA that can help doctors make the diagnosis.

“Pain, swelling, and stiffness in smaller joints — in the hands, toes, and elbow, for example — as opposed to one or two bigger joints, like the knee and hip, usually indicates a pattern more likely to be RA,” says Dr. Husni. Pain from RA is usually more symmetric in nature, occurring on both sides of the body. When you injure yourself or have an overuse injury, however, pain usually occurs in just one joint. Joint stiffness can occur with injuries or other conditions, but stiffness with RA typically occurs in the morning and can be overwhelming, explains Dr. Husni. “It’s not a joint stiffness that passes after a few minutes, but more like you can’t even move the covers to get out of bed.”

In addition to a physical exam and taking your history, your rheumatologist will order blood tests to help diagnose RA. They are used to look for high levels of inflammation in the body, as well as certain antibodies that can be seen in many but not all cases of RA, such as rheumatoid factor or anti-CCP antibodies. Imaging studies, such as X-rays or MRI scans, can also help detect RA or gauge its severity.

If rheumatoid arthritis is diagnosed, a rheumatologist will partner with you to develop a treatment plan that works best for you. That’s what happened with Liang Harris. After getting diagnosed with RA, she went to her mother’s rheumatologist and started treatment. It took about six months to find the right combo of medications, she recalls, but now — 11 years after being diagnosed with rheumatoid arthritis — she and her rheumatologist work together to keep her RA under good control.

Keep Reading

  • Remission and Low Disease Activity in Rheumatoid Arthritis: What It Actually Means
  • Preclinical Rheumatoid Arthritis: What Is It, Exactly?
  • Rheumatoid Arthritis Risk Factors: Here’s What Really Causes Rheumatoid Arthritis

Illnesses that Mimic Rheumatoid Arthritis

Joint pain is the hallmark of Rheumatoid Arthritis (RA), but it is also common in several other illnesses. Rheumatoid Arthritis is a chronic autoimmune disease that causes the immune system to attack its own tissues – which include the delicate tissues that encapsulate most joints, hence, the joint pains.

Nonetheless, RA is not the only condition which includes joint inflammation, fever, and fatigue as its symptoms. In fact, these are also common in several other conditions like Fibromyalgia, Osteoarthritis, Ankylosing Spondylitis, Psoriatic Arthritis, Gout, Lupus, and infectious arthritis.

Doctors believe early diagnosis and treatment is crucial to limiting potential tissue damage and preserving joint function, but the diagnostic process can be challenging. Diagnosis includes looking for clues that help distinguish the patient’s condition from other conditions, ruling out each possible diagnosis until only one is left. The process of distinguishing one disease from others is called the “differential diagnosis.” Now, let’s read through the article to find out if your joint pain is caused by RA or something else.

Fibromyalgia

This happens when the brain overreacts to pain signals, intensifying feelings of pain in different parts of the body. Fibromyalgia and RA are separate diseases, but some people have both.

Like RA, fibromyalgia is more common in women and runs in families, but the exact cause is unknown. Both are chronic in nature and can have periods of exacerbation and remission. However, Fibromyalgia typically does not cause swelling (except in children). It often causes tenderness in specific areas of the body. Fibromyalgia is not a degenerative condition and does not cause joint erosion and deformity.

Osteoarthritis

This occurs when the cartilage that acts as padding between the joints degenerates. The cartilage can wear down gradually over the year. It is characterized by joint pain that is worse after periods of inactivity. Joints may feel stiff and lose range of motion. Sometimes an affected joint is swollen and/or tender to the touch.

Although some people with osteoarthritis experience joint swelling, the swelling is usually mild and less notable than the moderate to severe joint swelling that is a hallmark of RA. But since Osteoarthritis is not a systemic (body-wide) autoimmune disease like RA, it is not accompanied by fatigue, fever, or flu-like symptoms.

Ankylosing Spondylitis

This is a form of inflammatory arthritis that primarily affects the spine, but it can affect other joints too.

People with this condition often experience morning pain, stiffness, and fatigue. Affected joints can also feel swollen and tender. Some also experience redness of the eye, light sensitivity, and blurred vision.

Unlike RA that commonly affects smaller joints first, Ankylosing spondylitis usually produces symptoms in the low back, hips, and/or shoulders. Both diseases can affect anyone; but RA is most frequently diagnosed in women ages 30 to 60 and ankylosing spondylitis is more frequently diagnosed in males under the age of 40.

Psoriatic Arthritis

As per the National Psoriasis Foundation, 85% of people with this condition also have psoriasis – a condition that can cause red, patchy areas of skin and pitted fingernails. However, a person does not need to have psoriasis to have psoriatic arthritis, which makes it relatively difficult to diagnose.

In contrast with RA that commonly affects the first and/or second knuckles of the hands, Psoriatic arthritis usually affects the distal joints of the fingers and toes. To provide more context, distal joints are the joints furthest away from the body, such as the third knuckle of a finger.

In addition, psoriatic arthritis usually causes fingers and toes to swell along their entire lengths, making them look like sausages, and RA causes swelling just at the affected knuckles.

Polyarticular Gout

Gout is a metabolic disorder that causes microscopic crystals to build up in a joint. Only one joint is affected in about 90% of gout cases. As for the other 10%, if the disorder affects two or more joints it is called polyarticular gout.

Gout causes joint pain, swelling, redness, and warmth, so when it shows up in two or more joints it may be initially mistaken for RA. Both RA and gout can cause fever, fatigue, and/or a general feeling of being sick. However, gout symptoms usually appear suddenly and without warning, but RA pain usually appears more gradually and is most notable in the first hour after waking.

Gout can be diagnosed or ruled out by drawing fluid from the affected joints and examining it under a microscope. People with rheumatoid arthritis rarely get gout.

Viral Arthritis

Experts estimate about 1% of arthritis cases to be viral arthritis wherein the viral infection leads to joint pain and swelling. Examples of these viruses are parvovirus B19, known for causing fifth disease (erythema infectiosum), painful joints and anemia. Other examples of viruses that can cause viral arthritis include enterovirus, rubella, HIV, and hepatitis B and C.

Viral arthritis results in inflamed joints that are swollen, tender, red, and warm to the touch.

There is no specific blood test for RA, but a blood test can usually show whether or not a person has or had a particular virus. The joint symptoms will typically go away once the viral infection is either treated or resolves on its own, though in some cases arthritis symptoms become chronic.

Lyme Disease

Lyme disease is a bacterial infection spread to humans by infected deer ticks and western black-legged ticks. Some people do not know they have been bitten, making the diagnosis challenging. A doctor may consider a Lyme disease diagnosis if the patient experienced a bullseye-shaped rash or has been in an area where deer ticks and Lyme disease thrive.

Like RA, Lyme disease can cause joint pain and fatigue. People with Lyme disease often report headaches and/or stiff necks. Lymph nodes may become swollen and muscles may ache, and fever may be accompanied by chills.

A blood test can show the presence of Lyme disease, but it cannot be done until 2 or 3 weeks after the tick bite, and the results are not always accurate. Experts recommend treating suspected Lyme disease with antibiotics as soon as possible, often before lab tests can confirm a diagnosis.

Septic Arthritis

Sometimes an infection in a joint can cause severe inflammation, pain, and swelling. Most septic arthritis is caused by a bacterium called Staphylococcus aureus. This occurs when a bacteria, virus, or fungus elsewhere in the body travels through the bloodstream and invades the joint. It can also occur when an infectious organism reaches the joint through a break in the skin though less common.

In most cases, just one joint is affected. But it may still result to an inflamed joint that is swollen, tender, red, and warm to the touch. People with infectious arthritis may also have a fever and/or feel unwell. Joint symptoms usually appear suddenly and are often severe, making the person affected unable to move or use the affected joint.

People who have weakened immune systems, including people who take RA medications, are at an increased risk for septic arthritis.

Lupus

A complex autoimmune disease, lupus can cause a wide range of symptoms that vary in severity, making it challenging to diagnose. Many people refer to lupus by its full medical name, systemic lupus erythematosus (SLE).

One of the most common symptoms of lupus is pain and swelling in the hands, knees, and other joints. People often report fatigue, fever, and a general feeling of being unwell.

A person with lupus may find it difficult to breathe and may experience light sensitivity, hair loss, mouth sores, and/or a skin rash, particularly over the face. Digestive difficulties and neurological problems, such as headaches and tingling, are also possible.

There are a lot of illnesses that mimic RA. There is no single lab test that definitively diagnoses RA, but there are tests you can take to make sure if your joint pain is caused by something else. We urge you to have yourselves checked. Luckily, we have a walk-in laboratory that can take your tests to put your mind at ease. here to find out more. After all, laboratory tests play a vital role in making sure that physicians make the correct diagnosis and determine the appropriate course of treatment.

Sources:

(https://www.arthritis-health.com/types/rheumatoid/what-rheumatoid-arthritis-ra)
(https://www.arthritis-health.com/types/rheumatoid/my-joint-pain-rheumatoid-arthritis-ra-or-spondyloarthropathy)
(https://www.arthritis-health.com/types/rheumatoid/my-joint-pain-caused-rheumatoid-arthritis-ra-or-crystal-arthritis)
(https://www.arthritis-health.com/types/rheumatoid/my-joint-pain-caused-rheumatoid-arthritis-ra-or-infection)

Are My Painful Joints Caused By Rheumatoid Arthritis (RA) or Something Else?

See Rheumatoid Arthritis (RA) Diagnosis

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Fibromyalgia vs. Rheumatoid Arthritis (RA)

This condition occurs when the brain overreacts to pain signals, intensifying feelings of pain in different parts of the body. Fibromyalgia and rheumatoid arthritis are separate diseases, but some people have both.

How is it similar to RA? Fibromyalgia can cause musculoskeletal pain as well as debilitating mental and physical fatigue. Like RA, fibromyalgia is more common in women and runs in families, but the exact cause is unknown. Both are chronic in nature and can have periods of exacerbation and remission.

See Lyme Disease and Rheumatoid Arthritis (RA) vs. Fibromyalgia

How is it different? Fibromyalgia typically does not cause swelling (except in children). It often causes tenderness in specific areas of the body, called tender points. Fibromyalgia is not a degenerative condition and does not cause joint erosion and deformity.

In This Article:

  • Are My Painful Joints Caused By Rheumatoid Arthritis (RA) or Something Else?
  • Is My Joint Pain Rheumatoid Arthritis (RA) or Spondyloarthropathy?
  • Is My Joint Pain Caused By Rheumatoid Arthritis (RA) or a Crystal Arthritis?
  • Is My Joint Pain Caused by Rheumatoid Arthritis (RA) or an Infection?
  • Is My Joint Pain Caused by Rheumatoid Arthritis (RA) or Another Autoimmune Disorder?
  • Rheumatoid Arthritis Overview Video

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Osteoarthritis vs. Rheumatoid Arthritis

Osteoarthritis occurs when the cartilage that acts as padding between the joints breaks down. The cartilage can wear down gradually, over decades—in fact, osteoarthritis is sometimes referred to as degenerative joint disease. When cartilage degeneration is triggered by an injury it is called post-traumatic osteoarthritis. Osteoarthritis is by far the most common type of arthritis.

See Osteoarthritis Symptoms and Signs

How is it similar to RA? Osteoarthritis is characterized by joint pain that is worse after periods of inactivity. Joints may feel stiff and lose range of motion. Sometimes an affected joint is swollen and/or tender to the touch.

How is it different? Although some people with osteoarthritis experience joint swelling, the swelling is usually mild and less notable than the moderate to severe joint swelling that is a hallmark of RA. Because osteoarthritis is not a systemic (body-wide) autoimmune disease like rheumatoid arthritis, it is not accompanied by fatigue, fever, or flu-like symptoms.

Whipple’s disease mimicking rheumatoid arthritis can cause misdiagnosis and treatment failure

Diagnosis of Whipple’s disease is often delayed, especially in cases without any clinical evidence of gastrointestinal involvement. WD predominantly affects middle-aged white men, which was also evident in our cohort. All patients in our cohort suffered from joint manifestations mimicking seronegative RA. While most patients suffered from an asymmetrical, intermittent arthritis at disease onset, they later presented with symmetric arthritis in more than half of the cases, when they were first admitted to our department. Apart from the pattern of involved joints the suspected diagnosis of RA was further supported by the chronic disease course, involvement of the small joints in all, and joint erosions in three patients. As the clinical manifestations were considered to be compatible with a diagnosis of RA, in all but one patient anti-rheumatic treatment was initiated. Joint involvement is a very common feature in WD and occurs in 40–80% of patients at least transiently . In contrast to the patients of this case series, joint manifestations in WD have been most often described as arthralgia or arthritis, predominantly affecting the large joints like knees, wrists, ankles, hips and shoulders, whereas involvement of the small joints have been by far less often reported . In our patients also small joints were affected and erosive joint manifestations were observed in almost half of these patients (compared to a frequency below 10% described in other cohorts ). Of note, we could detect erosions only in small joints. The fact that bone erosions of the small joints are rather characteristic for RA and are part of the 1987 ACR-classification criteria for RA might have led to the wrong diagnosis in the reported patients . As mentioned above it is possible that destructive arthritis is misinterpreted even by radiologists and that a wrong interpretation of radiographs may lead to wrong diagnoses. Thus, both rheumatologists and radiologists should increase their awareness for rare diseases like WD as a reason for erosive bone changes.

Another distinctive feature that might have contributed to a delay in diagnosing WD was the absence of gastrointestinal symptoms in almost all of our patients. In most cohorts of WD patients reported to date, 80–90% of the patients develop gastrointestinal symptoms with weight loss, diarrhea or both, at least at later stages of the disease. In some patients the phenomenon of delayed gastrointestinal symptoms for up to 6 years after the onset of WD-associated arthritis was described , suggesting that some of our patients might have developed gastrointestinal symptoms if remained untreated. Others described the occurrence of gastrointestinal manifestations under immunosuppressive treatment in undiagnosed WD-patients . In particular, treatment with TNF-alpha-inhibitors was reported in several cases to unmask WD by development of gastrointestinal symptoms . The patients in our cohort did not develop any relevant gastrointestinal manifestations even on long-term immunosuppressive therapy. Besides prednisolone or synthetic DMARDs, biologic DMARDs including TNF-alpha-inhibitors were used. Interestingly, Patient #1 had the longest disease course and immunosuppressive therapy and exhibited the most severe phenotype. But even in this case worsening of the arthritis and general symptoms developed slowly over time and were thus misinterpreted as the natural disease course of treatment-resistant RA. In retrospective, the lack of a sufficient treatment response with respect to arthritis should have prompted differential diagnoses, but unfortunately mainly led to switching of the immunosuppressive treatment regimen or even to treatment escalation to at least one or even more biological agents. Treatment-resistant rheumatoid arthritis, especially if seronegative, should lead to careful reevaluation. Arthritis that worsens during immunosuppression requires rigid exclusion of infection. Joint infections with bacteria of low pathogenicity such as atypical mycobacteria also need to be considered in patients with clearly established diagnosis of RA. Aspiration of synovial fluid or synovial biopsy for detection of bacteria by culture and PCR are required. Unfortunately, in case of treatment failures the availability of a growing number of new anti-rheumatic drugs often leads to a switch of medication rather than to a reevaluation of the diagnosis.

WD is a very rare condition and diagnostic procedures are at least partially invasive. Recently, an algorithm for the diagnosis of Whipple’s arthritis including PCR of synovial fluid, stools and saliva has been proposed . The patients of the present study, however, presented with inflammatory arthritis and therefore arthrocentesis was performed. As PCR was positive for TW in all tested patients of our cohort, the diagnostic work-up in all patients was completed but no further TW-diagnostic on saliva and stools was performed. Our data indicate, that performing TW-PCR during diagnostic work-up of synovial fluid as performed in our patients can be crucial for the diagnosis of TW-arthritis. In classic WD, PAS-positive foamy macrophages can be found in the lamina propria and the specificity of the result can be increased by detection of TW by PCR . Despite no or only mild gastrointestinal symptoms in three of our patients, PAS-positive macrophages were visible in duodenal biopsies and positive PCR-testing confirmed these findings. Especially in patient #1, who was characterized by a long disease course with a large number of insufficient immunosuppressive regimens, TW was detectable by PCR at all investigated sites, even in the skin. Detection of TW in the skin of patients with classic WD even without apparent skin manifestations has been described and may also be helpful for diagnosis when WD is suspected . The three patients of our study with PAS-positive macrophages in duodenal biopsies and positive PCR-testing for TW can be classified as definite classic WD . Duodenal biopsies of the remaining four patients were negative in PAS-staining and only two patients had a positive duodenal TW-PCR. The fact that in all patients PCR-testing was positive in synovial fluid from at least one inflamed joint supports the diagnosis of localized TW infection in these individuals . As mentioned, PCR-testing of saliva and stool samples to screen for TW in patients with unexplained articular pain, weight loss and unclear abdominal lymphadenopathy has been proposed by Fenollar et al. . In patients with mere TW-arthritis without any gastrointestinal symptoms TW-PCR of saliva or stool specimens may be difficult to interpret given the possibility of asymptomatic carriers.

Finally, in all patients WD was treated with either ceftriaxone followed by long-term trimethoprim/sulfamethoxazole or doxycycline combined with hydroxychloroquine. Treatment duration ranged between 12 and 20 months following the current treatment recommendations .

In one patient doxycycline was discontinued because of recurrent arthritis. Changing the antibiotic treatment regimen resulted in a prompt clinical improvement. In this patient an immune reconstitution inflammatory syndrome (IRIS) – as previously described in whipple’s disease- may be an explanation for the reoccurrence of arthritis . As this patient refused to undergo another joint puncture, a recurrence of the TW infection cannot be ruled out. Two patients had to be treated for 20 or 32 months, respectively, because treatment had to be changed several times due to side effects or insufficient clinical response. Ultimately, all patients achieved complete remission and required no further treatment during follow-up. All patients are still under close monitoring with regular visits at least twice per year in our outpatient clinic. The excellent response to antibiotic therapy with no relapse after treatment cessation strongly supports the diagnosis of WD-arthritis, even in the two patients that were positive for TW only in the PCR analysis of synovial fluids.

Those with rheumatoid arthritis (or RA) know all too well about the pain, stiffness, and deformity that it brings. What they may not know, however, is that those symptoms could be reflective of an entirely different condition that closely mimics rheumatoid arthritis. For instance:

Psoriatic arthritis causes similar joint pain and stiffness; yet unlike RA, the majority of patients experience psoriasis first – something that does not occur in RA.

Gout is a type of arthritis that leads to tenderness and swelling of the joints, often with such intense pain that even the slightest touch can be excruciating. Gout is caused by excess levels of uric acid, however, unlike RA.

Inflammatory erosive osteoarthritis causes inflammation to the joints; yet in IEO, inflammation will eventually subside. RA is a chronic, lifelong condition.

Ankylosing spondylitis primarily impacts the lower back between the spine and pelvis. Less common in women, AS is differentiated from RA by the inflammation occurring between the tendon and bone, rather than in the joint membrane lining as in RA.

Lupus can display as joint pain and swelling and is often confused with RA and/or is co-occurring. Lupus can, however, also include skin rash, fatigue and muscle aches.

Fibromyalgia pain is more widespread than RA, affecting soft tissue and muscles as well as joints. It also often leads to sleep problems and fatigue.

Lyme disease symptoms mimic those of both RA and the flu. It’s important for blood work to be done to confirm the presence of Lyme disease and to allow for proper treatment.

Pseudogout strikes suddenly, bringing intense pain to the joints along with warmth and swelling which can last for several weeks or even months.

Palindromic rheumatism, or palindromic arthritis, causes only temporary joint inflammation that subsides in as little as several hours, up to several days. It can also progress between joints before disappearing altogether.

Reactive arthritis, while extremely rare, is a type of arthritis that stems from an infection and typically affects joints in the feet and knees. It can also, however, inflame the skin, urethra, and eyes. Symptoms are usually gone within a year. Those who suspect they have rheumatoid arthritis should be sure to ask the doctor to rule out any of these similar conditions in order to allow for the most appropriate treatment. THE MEDICAL TEAM’s skilled home care providersare available to help those with RA or any other condition to improve quality of life. Contact usfor an in-home consultation to learn more!

Diagnosing Rheumatoid Arthritis

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Arthritis is an autoimmune condition in which the immune system mistakenly attacks healthy tissues in your body. In rheumatoid arthritis, your immune system attacks the joints—usually the small ones in the hands and feet—causing inflammation and pain. The inflammation sometimes affects organs, such as the eyes, lungs, and heart.

Several different tissues are involved in a joint’s function. A joint is the place where two bones meet to enable movement. Each one is contained in a capsule that produces synovial fluid, which lubricates the joint, helping it to move smoothly. Cartilage, which covers the surface of a bone at a joint, serves as a cushion to ensure the bones don’t rub against each other. The muscles, tendons, and ligaments surrounding the joint provide support and control movement.

When immune system cells attack the joints, they damage the thin layer of cartilage that covers each bone on both sides of the joint. The space between the bones narrows, and eventually inflammation can cause the bones to wear down. This can cause the joint to look misshapen.

As a result, people with rheumatoid arthritis experience joint pain, stiffness, swelling, fatigue, and limited function. These symptoms occur on both sides of the body. They are usually worse upon waking, but can last all day.

Rheumatoid arthritis affects people differently. For some, joint inflammation develops slowly over the course of several years. For others, it sets in quickly. Symptoms may be mild and easily controlled, or debilitating.

People with moderate to severe rheumatoid arthritis sometimes experience symptoms in cycles. There may be a period when the arthritis seems to improve or even goes into remission, during which you have no symptoms for weeks or months. Then symptoms may return suddenly in what is known as a flare.

During a flare, people experience increased inflammation, swelling, and pain. Symptoms can last anywhere from days to months before they seem to improve. In general, with each flare-up, the arthritis tends to worsen, involving more joints and lasting longer. Ultimately, the symptoms become persistent and don’t go away unless you get treatment.

Rheumatoid arthritis affects more women than men, and it can occur at any age. It most often tends to affect women who are in their 50s. The cause is unknown, although a combination of genetics and environmental factors seems likely. Some experts believe that a bacterial infection or a virus can trigger rheumatoid arthritis in those who are genetically susceptible.

Obesity and smoking may make you more susceptible to developing rheumatoid arthritis.

Left untreated, chronic inflammation can spread to other parts of the body, such as the blood vessels and lungs. Inflammation of the sclera, the white part of the eye, can lead to pain and redness.

A person with untreated rheumatoid arthritis is also at risk of developing coronary artery disease and atherosclerosis, in which the arteries become hard and narrow. These conditions may lead to heart attack and stroke. Rheumatoid arthritis can also cause inflammation in the lungs, leading to shortness of breath.

Some people with rheumatoid arthritis are at risk of Sjogren’s syndrome. In this autoimmune disorder, the immune system attacks and damages the salivary and tear glands, causing dry mouth and dry eyes.

There is no cure for the condition, but recently developed, highly effective medications have made the disease easier to manage. They often eliminate symptoms and remove physical limitations so you can continue your usual activities.

Doctors perform several tests to diagnose rheumatoid arthritis.

Diagnostic Tests

Your doctor takes a medical history and asks when your symptoms began, whether they have worsened, and which joints are painful. Then, he or she conducts a physical exam and orders diagnostic tests.

Physical Exam

Your doctor examines your joints to see how stiff or swollen they are. He or she may also ask you to walk or bend to observe how your affected joints have altered your movements. Knowing how many joints are painful and which ones are involved can help your doctor diagnose the condition. There are several types of arthritis, and they affect joints in different ways.

Blood Tests

In autoimmune disorders like rheumatoid arthritis, the immune system produces antibodies, or proteins, to attack healthy cells. This causes chronic inflammation. So doctors draw blood and measure a person’s white blood cell count. They also check for other signs of inflammation, such as high levels of C-reactive protein—made by the liver—and low iron levels.

Our doctors also check for antibodies linked to rheumatoid arthritis, such as rheumatoid factor and anti-cyclic citrullinated peptide. These substances are present in the blood of most people with rheumatoid arthritis. Blood tests for other conditions that can mimic rheumatoid arthritis, such as hepatitis C and parvovirus, are also performed; the results should be negative if you have the condition.

A doctor can’t rely on the results of an antibody test alone to diagnose rheumatoid arthritis, because a small percentage of people who have the condition test negative for antibodies. Some people who test positive never develop rheumatoid arthritis.

Doctors ultimately diagnose the condition based on a person’s symptoms in combination with the results of blood tests. These tests should be positive for rheumatoid arthritis and negative for other conditions that can mimic rheumatoid arthritis.

X-ray

Your doctor may order an X-ray—which uses electromagnetic radiation to produce images of the body—to assess the severity of joint destruction. Although this test is not useful in the early stages of rheumatoid arthritis, it can be used to monitor the progression of the disease. X-rays are done periodically—sometimes once a year—to determine if there is worsening damage in the joints.

Ultrasound

A doctor may order an ultrasound to see if you have any active inflammation, fluid buildup, and erosion of bone. These symptoms might not be detectable on an X-ray if you have an early form of the disease.

Ultrasound is frequently more sensitive than an X-ray in detecting inflammation of the lining of the joints.

MRI Scan

A doctor may order an MRI scan to better view the joints and determine whether there is any swelling. MRI scans use a magnetic field and radio waves to create two- or three-dimensional pictures of the body.

For 20 years, Frances Muller’s rheumatoid arthritis (RA) was misdiagnosed. A neurologist told her the pain in her hands was carpal tunnel syndrome. An internist told her the all-over aches were the flu. An orthopaedic surgeon said she had bursitis in both shoulders. “None of my symptoms made any sense,” and none of the treatments helped, says Muller, who lives in Scottsdale, Ariz. After she’d seen 13 other doctors, an orthopaedic surgeon who ordered an X-ray of her pelvis finally figured it out: there was no way she could have so much damage to her hips and not have RA.

Misdiagnosis is one of the most common medical errors, occurring in about 10 to 20 percent of cases, according to the National Center for Policy Analysis. It can lead to unnecessary or delayed treatments and physical and emotional suffering.

In rheumatology, where symptoms and diseases frequently overlap, even experienced and well-intentioned physicians can miss important clues. “For many rheumatic diseases, there’s no gold standard ,” says Don L. Goldenberg, MD, chief of rheumatology at Newton-Wellesley Hospital in Massachusetts. “You don’t biopsy it. There aren’t a lot of laboratory tests.” If patients are concerned, they should get a second opinion, he adds.

Overlapping Diagnoses

Here are some rheumatic diseases that are well known for being tricky to detect:

  • Sjögren’s syndrome is an autoimmune disease that attacks the body’s moisture-producing glands. It causes dry eyes and dry mouth, and can also damage organs such as the liver, lungs, kidneys and stomach. According to the Sjögren’s Syndrome Foundation, it takes patients an average of up to seven years to receive a diagnosis. Sjögren’s syndrome often is mistaken for conditions like fibromyalgia, chronic fatigue syndrome and allergic conjunctivitis (eye allergies).
  • Lupus is a disease in which the body attacks its own joints, skin, tendons and vital organs. Symptoms flare and then disappear. Doctors have dubbed lupus “The Great Imitator” because of its ability to look like so many other diseases, including rheumatoid arthritis (RA), scleroderma, rosacea, multiple sclerosis, Lyme disease, depression and fibromyalgia.
  • Fibromyalgia features a mix of symptoms that may include widespread pain, muscle spasms, mood disturbance, fatigue, insomnia, memory problems and irritable bowel syndrome. Fibromyalgia often is mistaken for RA, osteoarthritis (OA), Lyme disease, chronic fatigue syndrome, underactive thyroid, depression, and lupus.

Misdiagnosis Red Flags

To help you decide when it’s time to push for more answers or seek a second opinion, here are seven red flags that your doctor may have arrived at the wrong conclusion about your condition:

1) Your diagnosis is based exclusively on the results of a blood test.

In rheumatology, blood tests are done to check for antibodies—proteins the immune system makes when it is mounting an attack. But blood test results shouldn’t be the sole basis for a diagnosis, because they can be negative in people who do have arthritis, and positive when no disease is present. For example, antinuclear antibodies, which indicate the body is launching an immune attack on itself, can show up for a number of reasons. “I’d say that I see patients on a weekly basis who come to me and say, ‘I have lupus,’ because they tested positive for ANA,” says Robert Shaw, MD, a rheumatologist at the Carroll County Arthritis and Osteoporosis Center in Westminster, Md. Antinuclear antibodies (ANAs) may also be a sign of chronic infections, like sinusitis. Between 3 percent and 15 percent of healthy people also carry ANAs.

2) Your doctor has prescribed a treatment, but it isn’t working.

Trial and error is often a necessary part of unmasking an illness, but always let your doctor know if a drug or therapy is not helping. “A very important diagnostic test is whether somebody responds to treatment the way you think they should,” says Gordon D. Schiff, MD, who researches patient safety at Brigham and Women’s Hospital in Boston.

If a treatment is not working, that doesn’t mean the diagnosis is wrong. Some arthritis drugs work better in certain people than in others. Disease-modifying antirheumatic drugs can take weeks or even months to start working. Before you start on any new treatment, ask what to expect and establish a time frame for seeing results. If you aren’t getting better as quickly as you should, go back to your doctor for a medication adjustment. Or, if you feel the diagnosis just isn’t a good fit, get a second opinion.

3) You were diagnosed by a physician working outside his or her specialty.

Many people start the diagnosis process by visiting a family practice physician. But if you have a complicated case, it may be not be easy for such a generalist to reach the right diagnosis. Even if a primary care physician has correctly diagnosed your condition, you may benefit from having a rheumatologist on your team. Rheumatologists specialize in diseases that affect the muscles and joints, and they can make sure you’re treated appropriately.

4) Your doctor never ordered a key lab test.

While a diagnosis should never be based exclusively on test results, some conditions can’t be positively identified without specific tests. “If your doctor told you that you had gout, for example, but he failed to draw fluid from the joint to check for uric acid crystals, then you might not have gout,” Dr. Schiff says. Other diseases mimic gout, including bursitis, OA, and pseudogout, and they require different treatments. Find out what tests are typically ordered for your condition by checking reputable sources, including the Centers for Disease Control and Prevention; the National Institute of Arthritis, Musculoskeletal and Skin Diseases; the Arthritis Foundation; and the American College of Rheumatology.

5) Your symptoms don’t match your diagnosis.

Many doctors are so busy that they listen to one or two of a patient’s complaints before starting down a diagnostic path, and the resulting conclusion may not quite fit. A patient who comes in with all-over aches in January is more likely to have the flu than lupus, but that won’t always be the case. As soon as your doctor gives you a diagnosis, hit the library and the Internet. Check reliable references to find out what symptoms are typical for the condition you’ve been told you have.

6) You didn’t get a physical exam.

Fewer doctors are performing regular physical exams on their patients, which can lead to mistakes. When a rheumatologist touches your knuckles, for example, joints that are red, swollen, hot and soft may point to an inflammatory form of arthritis, like RA. Joints that are cool and hard may be a sign of OA. If you didn’t get an exam, ask for one.

7) Your doctor didn’t ask enough questions about you.

Medical history questions are important because they can open up diagnostic possibilities the doctor may not have considered. A thorough family history, for example, can reveal genetic predispositions to disease. Other questions, like where you’ve lived or the kind of work you do, may be critically important to your diagnosis. People with particular jobs face a higher-than-average risk of repetitive strain syndromes, such as carpal tunnel or low back pain.

Putting the Puzzle Together

For many people, the problem of misdiagnosis is resolved relatively quickly, with no lasting impact. But Muller says years passed and her pain never went away, despite multiple explanations from doctors. Now when she hears about other patients who are suffering without answers, she has this advice: “Try to find a doctor that just sits and listens to you,” she says. “When a doctor stops listening to you, you need to go to another doctor.”

An arthritis diagnosis can change your life in many ways, but don’t accept that news too quickly. It is surprisingly common for arthritis to be misdiagnosed, and even if you do have arthritis the doctor may specify the wrong type. Any time a doctor orders a lab test, X-ray, magnetic resonance imaging (MRI) scan or ultrasound, find out what the test determined. If the results raise concerns, make sure you are scheduled to see the doctor again for a follow-up appointment.

Related Resources:

  • Lab Test Guide
  • Finding the Right Doctor
  • Tips to Communicate with Your Doctor
  • Medical Imaging for Arthritis Diagnosis
  • Diagnosing Arthritis

A Case of Multiple Myeloma Misdiagnosed as Seronegative Rheumatoid Arthritis and Review of Relevant Literature

Abstract

Multiple myeloma (MM) is a malignant plasma cell proliferation producing large numbers of monoclonal immunoglobulins. Typical MM symptoms include anemia, renal failure, hypercalcemia, and bone pain. Atypical symptoms have rarely been reported in the literature. We report a case of a 58-year-old male who presented with symmetrical inflammatory polyarthritis and was misdiagnosed with seronegative rheumatoid arthritis (RA). After failing many RA treatments and with further workup, the diagnosis of MM was made. This rare manifestation of MM carries a diagnostic challenge and causes a significant delay in treating such patients. Here, we report this unusual initial presentation with review of several cases in the English literature describing similar presentations.

1. Introduction

Multiple myeloma (MM) is a clonal plasma cell malignancy that accounts for approximately 10% of hematologic malignancies . In the United States, the lifetime risk of getting MM is 1 in 132 (0.76%) . In patients presenting at under 60 years of age, the 10-year survival rate is about 30% . The diagnosis of MM is often delayed due to lack of recognition of the most common presenting symptoms, such as fatigue, anemia, renal insufficiency, and hypercalcemia. An atypical manifestation could put an even greater challenge on the diagnosis and subsequently cause a delay in treatment. We describe a 58-year-old male who presented with symmetrical inflammatory synovitis as a first sign of MM, and we report the relevant literature.

2. Case Presentation

A 58-year-old male was referred to the rheumatology clinic for evaluation of arthralgia of the hands, wrists, and elbows. The patient’s symptoms started six months prior and gradually worsened. The patient endorsed swelling of the hands and wrists, difficulty making fists, as well as morning stiffness lasting more than thirty minutes. He denied any constitutional symptoms such as fevers, chills, weight loss, decreased appetite, or night sweats. Review of systems was negative for alopecia, dry eyes, dry mouth, mouth sores, and skin rash. The patient also denied any recent travel, tick bites, or sick contacts. He never smoked and consumed alcohol on an occasional basis. The patient had a past medical history of osteoarthritis, with a surgical history significant for multiple procedures, including bilateral shoulder replacement for severe osteoarthritic changes, carpal tunnel repair of the right side, and laminectomy of the cervical and lumbar spine. Clinical exam revealed normal vitals, with benign head, eye, ear, nose, throat, cardiopulmonary, and abdominal exams. No lymphadenopathy or bruises were observed. Musculoskeletal exam revealed synovitis of the second through fifth metacarpophalangeal (MCP) and proximal interphalangeal regions bilaterally, with swelling and tenderness of the wrists with warmth to touch. In addition, there were 30-degree fixed contractions of the elbows. As per the patient, there was no history of psoriasis or nail changes, which was confirmed on physical exam as well. Laboratory data showed white blood cells of 12,000/mm, hemoglobin of 9.7 g/dl, hematocrit of 30.9%, C-reactive protein of 40 mg per liter (reference value <8), and erythrocyte sedimentation rate of 50 mm per hour (reference range 0 to 15). Laboratory testing of liver function, calcium, thyroid function, uric acid, renal function, and urinalysis was normal. Other normal or negative tests included antinuclear antibody, rheumatoid factor (RF), anti-cyclic citrullinated peptide (anti-CCP) antibodies, hepatitis B panel, hepatitis C antibody, QuantiFERON-TB Gold test, and angiotensin-converting enzyme. The patient was seen by an outside rheumatologist and treated initially with prednisone 20 mg/d and methotrexate, which was quickly escalated to a dose of 20 mg/weekly, with no response after three months of treatment. He was subsequently started on antitumor necrosis factor inhibitors.

Six months later, a follow-up visit showed persistent symptoms. Alternative anti-TNF inhibitors were tried with no improvement. Further workup included X-rays of the hands and wrists, which showed mild degenerative changes only. Chest X-ray revealed no pathology. The patient underwent MRI of the right hand, which showed synovial thickening of the radiocarpal joint and MCP joints with flexor tendon tenosynovitis, compatible with inflammatory arthropathy (Figure 1). Further questioning of the patient revealed a family history of primary amyloidosis in his mother. Serum calcium, uric acid, and creatinine remained normal during the time of RA treatment. As a result, serum protein electrophoresis (SPEP) and urine protein electrophoresis were sent. Interestingly, SPEP was positive for M-band. The patient was then referred to hematology for further evaluation and underwent a bone marrow biopsy, which was positive for more than 40% plasma cells, as well as being Congo red stain negative, findings consistent with MM. FISH analysis was positive for monosomy 13 in 88% of the cells. The patient then started treatment for MM with bortezomib and dexamethasone. Six-month follow-up showed complete resolution of joint swelling, with significant improvement in pain of the hands, wrists, and elbows. His MM remained quiescent with chemotherapy, and the patient did not require bone marrow transplant.

Figure 1 MRI of the right hand without contrast. Short T inversion recovery (STIR) showing tenosynovitis of the flexor tendons of the second and third digits and synovitis of the second, third, and fourth MCP joints.

3. Discussion and Literature Review

Multiple myeloma is a cytogenetically heterogeneous, clonal plasma cell proliferative disorder, which can produce a monoclonal immunoglobulin, and which accounts for approximately 1% of neoplastic diseases and 10% of hematologic cancers . The American Cancer Society estimates that 30,770 new cases of MM will occur in the US in 2018, with approximately 12,770 deaths expected to occur . In 2014, the International Myeloma Working Group released updated diagnostic criteria (Figure 2). The incidences of presenting symptoms of MM are bone pain (58%), fatigue (32%), pathologic fracture (26 to 34%), weight loss (24%), paresthesias (5%), and fever (0.7%) .

Figure 2 2014 Updated Diagnostic Criteria of Multiple Myeloma by the International Myeloma Working Group.

Rare presenting symptoms of MM can cause a significant delay in treatment and lead to unfavorable outcomes. Our case’s unusual initial presentation of MM prompted a literature review to look for other reported cases presenting as inflammatory arthritis. We have performed a systematic search of English literature on PubMed from 1991 to 2018 using the keywords “multiple myeloma” and “monoclonal gammopathy” with “peripheral inflammatory arthritis,” “rheumatoid arthritis,” and “rheumatologic diseases.” 344 articles were obtained and reviewed. The articles collected were only cases which resembled or had close presentation to our patient and are summarized in Table 1.

Number of patients Affected joints Serology Monoclonal gammopathy diagnosis Reference
6 Wrists and shoulders are the most commonly involved joints Five patients were negative for RF and anti-CCP antibodies
One patient was positive for RF and anti-CCP antibodies
Four patients diagnosed with MGUS and two patients diagnosed with MM Srinivasulu
2 Wrists, hands, TMJ, and shoulders Negative RF
Negative anti-CCP
MM associated with amyloid arthropathy Alpay
1 Hands, wrists, shoulders, and knees Negative RF
Anti-CCP antibodies were not reported
MM Molloy
1 Hands, knees, and feet Negative RF
Anti-CCP antibodies were not reported
MM Ardalan
9 Hands, wrists, shoulders, and knees. One case had sacroiliitis Negative RF
Anti-CCP antibodies were not reported
Two patients diagnosed with MM. Seven patients diagnosed with MGUS Jorgensen
1 DIP joints, PIP joints, wrists, knees, and ankles Negative RF
Negative anti-CCP antibodies
MM with amyloidosis Roca
4 DIP joints, PIP joints, MCP joints, and wrists Negative RF
Anti-CCP antibodies were not reported
MGUS Vitali
1 Knees Negative RF
Negative anti-CCP antibodies
MM Agarwal
1 Hands and wrists Negative RF
Anti-CCP antibodies were not reported
MM with amyloidosis Fujishima
1 Hands and wrists Positive anti-CCP antibodies
Negative RF
MM Edavalath
4 3 of the 4 patients had polyarthritis of hands and wrists RF and anti-CCP antibodies were not reported MM and amyloidosis Bornstein
RF: rheumatoid arthritis; anti-CCP antibodies: anti-cyclic citrullinated peptide antibodies.

Table 1 Literature review table.

The largest series, reported by Jorgensen et al. in 1996, included nine patients with monoclonal gammopathy (MG), either MM or monoclonal gammopathy of uncertain significance, who developed inflammatory chronic arthritis simultaneously or after the diagnosis of MG. Interestingly, all of the patients were seronegative for rheumatoid factor, and the majority had hand and wrist involvement, including two patients who had distal interphalangeal joint involvement not typical of RA . Vitali et al. published a similar series of four cases in 1991, in which, like Jorgensen et al., the MG was found prior to or during the development of arthritis. Two patients had rheumatoid-like, symmetric polyarthritis of the MCP joints and wrists . DIP involvement was reported in this series as well. In addition, RF was negative in four cases.

In 2003, Fujishima et al. described one case of symmetrical polyarthralgias and multiple joint swellings with negative RF, mimicking RA. Bone marrow biopsy was consistent with MM, and synovial biopsy showed amyloid arthropathy . Another similar observation of a case of MM presenting as acute interstitial nephritis and RA-like polyarthritis was reported by Ardalan and Shoja in 2007. In this case, the patient initially presented with rapidly progressive renal failure and underwent renal biopsy, which was consistent with acute interstitial nephritis . Two months later, he returned with symmetric polyarthralgias of the hands and feet, with associated knee effusions. Further workup with bone marrow aspiration and biopsy revealed MM, and the RF was negative. Another interesting unusual presentation described by Molloy et al. in 2007 highlighted a case of erosive seronegative inflammatory arthritis in association with bilateral carpal tunnel syndrome as rare symptoms of MM . In 2009, Alpay reported two patients with symmetric polyarthralgias of the hands, wrists, shoulders, and temporomandibular joints, both diagnosed with MM and found to have amyloid deposition seen on synovial biopsy .

More recently, Srinivasulu et al. reported a case series of 6 patients in 2012, 5 of which were seronegative for RF and anti-CCP antibodies and 1 was positive for both . Two separate cases of MM presenting as inflammatory polyarthritis were reported by Fedric and Agarwal. Fedric described a 72-year-old woman who presented with bilateral symmetric synovitis of the knees, ankles, wrists, and metacarpophalangeal joints, who was diagnosed with MM associated with amyloidosis. Agarwal described MM in a case of a young male who presented with polyarthralgias and rash . A case of MM masquerading as seropositive RA with cutaneous amyloid nodules thought to be RA nodules was described by Edavalath in 2017 . Most recently, Bornstein et al. published a series of four cases of various hematological malignancies mimicking rheumatic syndromes. One of these cases was a patient with seronegative inflammatory polyarthritis of the wrists, MCP and PIP joints, who was later found to have MM with restrictive cardiomyopathy, secondary to amyloidosis, and died shortly thereafter . The association between monoclonal gammopathy (MG) and rheumatic disease has been investigated and showed increased prevalence of MG among patients with rheumatic diseases .

From our in-depth review, we have observed that the hands and wrists are the most commonly involved joints in patients with MG mimicking RA, and that almost all patients have negative RF. Of note, anti-CCP antibody was not mentioned in the older references since it was not discovered at that time. Our case illustrates an atypical presentation of MM mimicking seronegative rheumatoid arthritis, which carried a diagnostic challenge for physicians and caused a delay in the treatment of a life-threatening malignancy. Lack of response to RA treatment should prompt the physician to reexamine the initial diagnosis and think of alternatives. Increased awareness of atypical symptoms for serious diseases such as MM is critically important among health care providers and should become more emphasized in future practice.

Consent

Written consent was obtained from the patient for publication.

Conflicts of Interest

The authors declare that they have no conflicts of interest.

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