A 30 year-old woman comes to you with recent onset of pain in multiple joints mostly the small joints of the hands and feet, both wrists and elbows and ankle joints. There is pain in the forefoot on both sides. The patient feels miserable.
What information do you need? What questions will you ask?
Viral diseases such as rubella, measles, hepatitis B and C, Parvovirus 19 all cause joint pains. In Karachi in 2017 and 2018 there was an outbreak of chikungunya disease (one of the alpha viruses). Mumps can also cause arthralgia.
- Did you have fever at the beginning of your illness and do you have it now?
- Did you have sneezing, watery eyes, cough and throat irritation at the start of the illness?
- Did you have a rash on your face (Parvovirus) or all over the body (rubella and chikungunya)?
- Did you have a recent severe illness with fever and rash all over your body from which you have now recovered? (Adult measles).
- Do you feel that your eyes are turning yellow and do you have pain in your upper abdomen and have you lost your appetite and have nausea? Hepatitis B and C.
- Do have pain on either side of your face when opening your mouth? Mumps.
When you are asking these questions you must have the likely diseases which can cause these symptoms, in your mind.
In the rainy season in tropical and subtropical countries like Pakistan and India, mosquitoes abound. The Aedes aegypti and Aedes albopictus mosquitoes transmit chikungunya, dengue and and the Zika virus.
In chikungunya 3-7 days after a mosquito bite there is fever which lasts for 4-6 days, polyarthralgia begins two to five days after onset of fever and commonly involves multiple joints (often 10 or more joint groups usually in the hands, wrists and ankles). Pain may be intense and disabling, leading to immobilization.The most common skin manifestation is macular or maculopapular rash (usually appearing three days or later after onset of illness and lasting three to seven days). The rash often starts on the limbs and trunk, can involve the face, and may be patchy or diffuse. Pruritus has been reported in 25 to 50 percent of patients. Additional manifestations may include headache, myalgia, facial puffiness, and gastrointestinal symptoms. Atypical dermatologic manifestations include bullous skin lesions and skin hemorrhage may occur. Pain in the external ear is caused by chondritis. on examination of the joints there may be periarticular edema or swelling or large joint effusions. Peripheral lymphadenopathy (most often cervical) may be present. Conjunctivitis may be observed. The most common laboratory abnormalities are lymphopenia and thrombocytopenia. Hepatic transaminases and creatinine may be elevated. High viral load during the acute illness was associated with poor prognosis in the post-acute phase in a large series in India and can be fatal.
If your patient has Chikungunya after she recovers from the acute attack do you need to advise her to come for a follow up and for how long? What complication is she likely to develop in her joints?
Approximately half of patients develop chronic inflammatory arthritis (rheumatoid arthritis, nonspecific post-viral polyarthritis, or seronegative spondylitis); other manifestations included arthralgia and other musculoskeletal pain conditions (eg, fibromyalgia, frozen shoulder, and plantar fasciitis). Follow up for 18 months at least.
How long are the symptoms of arthralgia and/or arthritis likely to last?
Many patients (upto 35%) have significant joint pains for 6-18 months. Occasionally they may last for several years.
What can the patient be suffering from other than viral arthritis? What is the differential diagnosis?
I would like to rule out rheumatoid arthritis which in its initial stage is difficult to distinguish from other inflammatory arthritides. It is important to make an early diagnosis of RA as disease-modifying antirheumatic drugs (DMARDs).
I would like to rule out other conditions by inquiring about symptoms suggesting an alternative diagnosis, such as psoriasis, inflammatory bowel disease (IBD), or a systemic rheumatic disease such as systemic lupus erythematosus (SLE). Gout is unlikely because she is a young woman. It is older women nearing or in the post menopausal state who tend to get gout.
Can gout occur in children?
It is rare as children, both pre-pubescent boys and girls, have very low levels of uric acid below those of adults. When gout occurs in children we should look for marked hyperuricemia due to urate overproduction, such as inherited defects in enzymes of purine metabolism or diseases with greatly increased rates of cell proliferation, or due to severely impaired renal uric acid clearance, as in familial juvenile hyperuricemic nephropathy.
What will you look for in the physical examination?
In the physical examination of the joints I will assess for synovitis, including the presence and distribution of swollen or tender joints and limited joint motion; I will look for extraarticular manifestations, such as rheumatoid nodules; and signs of diseases, such as SLE or psoriasis, which are included in the differential diagnosis.
What is the cause of the pain in her forefeet?
It is caused by plantar fasciitis which is a common feature of inflammatory arthritis of viral or non-viral origin.
Is she likely to have rheumatoid nodules and other extraarticular manifestations of RA?
No she is unlikely to have any extraarticular manifestations as she has had the symptoms for a few weeks. These develops in months or years. I will rely on laboratory findings to confirm or rule out RA.
What is morning stiffness?
Morning stiffness is a common feature of those with active RA; it can be defined as “slowness or difficulty moving the joints when getting out of bed or after staying in one position too long, which involves both sides of the body and gets better with movement
What are the diagnostic criteria for RA? How will you determine that the patient has RA? How will assessment of the joints help you determine that your patient has RA? Does the duration of a few week help you make a diagnosis of RA?
You will find the answers to these questions given below.
- Inflammatory arthritis involving three or more joints.
- Positive rheumatoid factor (RF) and/or anti-citrullinated peptide/protein antibody (such as anti-cyclic citrullinated peptide [CCP])) testing.
- Elevated levels of C-reactive protein (CRP) or the erythrocyte sedimentation rate (ESR).
- Diseases with similar clinical features have been excluded, particularly psoriatic arthritis, acute viral polyarthritis, polyarticular gout or calcium pyrophosphate deposition disease, and systemic lupus erythematosus (SLE).
- The duration of symptoms is more than six weeks.
- Some patients may not fall into these 2010 guidelines of American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) classification criteria for RA.
Inflammatory arthritis — Arthritis is typically present in the metacarpophalangeal (MCP) and proximal interphalangeal (PIP) joints of the hands. The wrists are also commonly involved, as are the metatarsophalangeal (MTP) joints in the feet, but any upper or lower extremity joint may be affected. Symmetric polyarthritis, particularly of the MCP, MTP, and/or PIP joints, strongly suggests RA. Although distal interphalangeal (DIP) joint disease can occur in patients with RA, DIP involvement strongly suggests a diagnosis of osteoarthritis or psoriatic arthritis.
Is RF positivity diagnostic for RA?
RF factor is positive in 70-80% of patients in RA but is also positive in 1-10% of healthy people and the incidence rises with age. The RA factor is also positive in SLE, virtually all patients with mixed cryoglobulinemia (usually caused by hepatitis C virus [HCV] infections), and in those with many other inflammatory conditions. Higher titers of RF (at least three times the upper limit of normal) have somewhat greater specificity for RA.
Antibodies to citrullinated peptides/proteins are usually measured by enzyme-linked immunosorbent assays (ELISAs) using CCPs as antigen. Anti-CCP antibodies have a similar sensitivity to RF for RA but have a much higher specificity (95 to 98 percent) The specificity is greater in patients with higher titers of anti-CCP antibodies (at least three times the upper limit of normal). Another test, anti-mutated citrullinated vimentin, gives similar results to anti-CCP and is used as an alternative in some laboratories
Acute phase reactants — Elevations of the ESR and/or CRP level are consistent with the presence of an inflammatory state, such as RA. Normal acute phase reactants may occur in untreated patients with RA, but such findings are very infrequent. The degree of elevation of these acute phase reactants varies with the severity of inflammation.
What if RF and anti-CCP are persistently negative in this patient but with time she fulfills the other criteria of RA?
She would be considered to have seronegative RA – Patients who lack both RF and anti-CCP antibodies may be diagnosed with RA based upon findings otherwise characteristic of RA if appropriate exclusions have been met. Such patients with seronegative RA differ from anti-CCP-positive patients genetically and in their environmental risks, disease severity, and clinical responsiveness to some medications.
Recent onset RA – Patients with disease for less than six weeks may be diagnosed with RA based upon findings otherwise characteristic of RA, including anti-CCP antibodies, if testing for viral serologies is negative and if other appropriate exclusions have been met.
Can she have gout or pseudogout?
Gout tends to occur in men more commonly and in older women. If the uric acid is raised in a young women check out her renal function as it rises in CKD (chronic kidney disease)
Crystalline arthritis — Crystalline arthritis (gout and pseudogout) can become chronic and even assume a polyarticular distribution. The diagnosis is established by the finding of urate or calcium pyrophosphate crystals, respectively, in synovial fluids. The presence of tophi on physical examination, the detection of serological markers of RA, and the characteristic appearance of gouty erosions are also useful in distinguishing RA from polyarticular gout.
Which drugs are likely to cause hyperuricemia?
Below is a table of drugs associated with hyperuricemia.
|Diuretics (thiazides and loop diuretics)|
|Cyclosporine and tacrolimus|
|Laxative abuse (alkalosis)|
Why are older patients with heart disease likely to have hyperuricemia?
They will have been prescribed diuretics either thiazide or loop for fluid retention and/or hypertension, will be on low dose aspirin for antiplatelet therapy, will be on fluid restriction and salt restriction. All these therapies and treatment strategies cause hyperuricemia.
What is palindromic arthritis or palindromic rheumatism
Palindromic rheumatism is characterized by episodes of joint inflammation sequentially affecting one to several joint areas for hours to days, with symptom-free periods that may last from days to months. Some patients presenting with this syndrome eventually develop a well-defined rheumatic disease, the most common being RA (ranging from 28 to 67 percent); some of the remaining patients develop SLE and other systemic disorders. Patients with anti-CCP antibodies appear more likely to progress to definite RA]. Close follow-up and specific serologic evaluation can help distinguish among these disorders.
What is reactive arthritis?
Reactive arthritis is considered when there is:
- History of recent urethritis or enteric infection (bacterial dysentery most often)
- Asymmetric pattern of joint involvement
- Symptoms or signs of enthesopathy like the back of the heel or under surface of the heel(inflammation at the site where a tendon inserts into a bone, eg, the insertion point of the Achilles tendon into the heel or the plantar fascia in the calcaneus)
- Keratoderma blenorrhagica or circinate balanitis
- Radiologic evidence of sacroiliitis and/or spondylitis
- The presence of human leukocyte antigen (HLA)-B27
What is fibroblastic rheumatism?
Fibroblastic rheumatism, a rare disease of unknown etiology, shares the features of arthralgia, arthritis, and nodules with RA. Flexion contractures of the fingers occur in most patients, while thickened palmar fascia is noted in about one-half of reported cases. Biopsy of a nodule or thickened skin typically reveals increased thickness of collagen fibers and fibroblastic proliferation. Decreased elastic fibers and the presence of myofibroblasts are noted in approximately 50 percent. Radiographic findings are variable, but periarticular osteopenia and erosions may be noted.
Due to the rarity of fibroblastic rheumatism, there is no well-established treatment. Progressive disease may lead to sclerodactyly and ankylosis of affected joints.
how does psoriatic arthropathy differ from RA?
Chronic arthritis in sarcoidosis may be oligoarticular or polyarticular and can appear similar to RA in some patients. It most frequently affects the ankles, knees, hands, wrist, and MCP and PIP joints, and it is frequently associated with parenchymal pulmonary disease.
This disorder is distinguished from RA by the following findings:
- Elevated serum concentrations of angiotensin-converting enzyme (ACE) are found in up to 50 percent of patients.
- A chest radiograph may reveal characteristic findings of sarcoidosis.
- The pattern of acute arthritis with Lofgren’s syndrome in patients with sarcoidosis is not observed in those with RA.
The woman we are examining says that the arthritis causes pain most in both the ankles, but moves to other joints too. These joints get better after a few days but a new joint becomes painful. She also complains of red blotchy nodules on her shins which clear up in a few weeks but fresh ones recur. What is she suffering from?
She has Lofgren’s syndrome which occurs in sarcoidosis. She has erythema nodosum on her legs. I would do an X Ray chest to look for hilar lymph nodes.
What is Lofgren’s syndrome?
Löfgren syndrome, is observed in <5 to 10 percent of patients with sarcoidosis, is the combination of erythema nodosum (EN), hilar adenopathy, migratory polyarthralgia, and fever seen primarily in women. It often causes bilateral ankle pain. Men with acute sarcoidosis may present with signs of bilateral ankle arthritis typical of Löfgren syndrome, but without EN. The presence of all features of the Löfgren syndrome has a 95 percent diagnostic specificity for sarcoidosis, allowing a clinical diagnosis to be made without biopsy
What is the treatment of seronegative arthritis?
For seronegative arthritis rule out chikungunya in a susceptible population, Think of polymyalgia rheumatica in the elderly (60 plus) population. They tend to respond to steroids initially but may develop seropositive RA and the treatment must be then changed accordingly. Also be on the lookout for Giant Cell Arteritis (GCA) in the elderly and steroids will be the mainstay of therapy.
What are you going to think of in a patient who has a painful puffy hand with edema?
RS3PE syndrome – The RS3PE syndrome refers to Remitting Seronegative Symmetrical Synovitis with Pitting Edema, also described as the puffy edematous hand syndrome or distal extremity swelling with pitting edema.
In this syndrome, distal symptoms and signs, often of sudden onset, are pronounced, though careful musculoskeletal examination will usually also disclose some degree of limited range of motion about the shoulders. Swelling, which is usually pitting, extends over the dorsa of the wrists to the metacarpophalangeal joints, producing the appearance of a “boxing glove,” with limited range of motion of the hands and wrists. Assays for rheumatoid factor and anti-CCP are negative. Ultrasound (US) and magnetic resonance imaging (MRI) demonstrate prominent extensor tenosynovitis of the extensor tendon of the forearms and hands, with lesser amounts of flexor tenosynovitis and synovitis of the metacarpophalangeal and proximal interphalangeal joints . An association with solid tumors and hematologic disorders has also been reported, but in clinical practice such an occurrence is rare . The patient will respond quickly to prednisolone 10mg in the night and 5mg in the morning.
I hope you have enough material to sail through an viva voce examination based on multiple joint pains. Have fun