Inflammatory myositis requires long-term potent immunosuppression and it's important to be certain about the diagnosis.
Dr Andrew Jordan presents a common clinical scenario and works through the reasoning for ordering each test, what questions are most useful to help diagnose this condition and a simple approach to management.
A 56-year-old female presents with three months of increasing pain and weakness of her arms and legs. She is now struggling to get out of seats or out of bed and can’t walk for more than 10 minutes when previously she was extremely fit. She struggles to lift her arms to do household chores or even wash her hair. She has recently had two falls where her legs seemed to give way. She has pain in both the upper arms and thighs in a diffuse distribution, correlating with muscles rather than joints. She is markedly fatigued. She reports mild exertional dyspnoea but does not have a cough or dysphagia. She is now unable to work in retail.
My initial thoughts with this history are a primary muscle disorder, although differentials could also include polymyalgia rheumatica (although she is on the younger age spectrum for this) or a broad range of neurological disorders (e.g. myasthenia gravis, motor neurone disease). I specifically ask about medication use that may cause a myopathy (statins, long-term prednisone, colchicine or excessive alcohol use).
Examination shows marked proximal muscle weakness with inability to lift her hands above shoulder height or do a straight leg lift in a supine position. She needs assistance to get up from the examination bed and get out of a seat. Distal power in upper and lower limbs is normal. There is weakness of neck flexion. There is no peripheral joint synovitis. Reflexes in the upper and lower limbs are normal. There is visible periungual erythema. She has a notable rash: an erythematous, dusky rash over her upper torso (shawl sign) and deltoid region. There is also puffiness around her eyelids (heliotrope rash) and erythema over the dorsum of the PIP and MCP joints in her hands (Gottron papules). This rash is highly suggestive of dermatomyositis.
She needs investigations to confirm my provisional diagnosis. CK is 4,800 (N<200). ALT is 270 (N<40) and AST is 343 (N<40) but the rest of the liver function test is normal. ESR is 96 (N<20) and CRP is 25 (N<5). ANA is 1:2560 speckled pattern with positive results for anti-Mi2 antibodies. ENA, dsDNA and ANCA are negative.
The investigations suggest an inflammatory autoimmune myositis and the classic skin rash makes it highly likely this is dermatomyositis. Anti-Mi2 antibodies are associated with dermatomyositis with sudden onset illness, shawl sign and a generally favourable response to treatment.
Investigations for muscle weakness and high CK can often be long and complex. This is often necessary given the broad differential diagnoses. Inflammatory myositis requires long-term potent immunosuppression and it is important to be certain about the diagnosis.
Typical investigations for high CK and muscle weakness may include NCS/EMG (to assess for myopathy and exclude peripheral neuropathies), MRI scan of affected muscles to assess for muscle oedema or muscle atrophy and a definitive diagnosis is often achieved with a muscle biopsy. Muscle oedema on MRI scan can also be used to help target the location of the biopsy as myositis may be patchy and targeted biopsies can reduce false negative rates. If there are neurological signs, then consideration should also be given to imaging the brain and spinal cord.
I felt confident to make a diagnosis of dermatomyositis based on her classic clinical presentation and autoimmune serology. Many specialists would elect to confirm her diagnosis with a skin or muscle biopsy given the potential morbidity associated with immunosuppression.
Dermatomyositis has a relatively strong association with malignancy, with around 20% of patients having a concurrent malignancy. It is very important to do thorough age-appropriate cancer screening. Recently, she’d had a negative Pap smear. I screened with mammogram, CT chest, abdomen and pelvis as well as endoscopy and colonoscopy. These were all normal. If there is a history of smoking or southeast Asian ethnicity, then nasopharyngeal endoscopy should be considered to exclude oropharyngeal malignancy.
Interstitial lung disease can occur in dermatomyositis and this may warrant stronger immunosuppression if it is present. CT chest did not show any evidence of interstitial lung disease and pulmonary function testing was normal.
I started prednisone 75mg daily (1mg/kg). I elected to use methotrexate as a steroid sparing agent. I utilised this with some caution given the high transaminases, however, AST and ALT are both present in muscle tissue and I felt they were most likely raised due to the myositis.
She was given calcium and Vitamin D supplementation. Bone mineral density scan showed osteopenia, so she was given a single infusion of intravenous zoledronate to prevent steroid-induced osteoporosis.
I use a proton-pump inhibitor to prevent peptic ulceration/gastritis from high-dose prednisone. There is an increase in risk of pneumocystis jiroveci pneumonia (PJP, previously known as PCP) infection with long-term high dose prednisone, so I use PJP prophylaxis until prednisone dose is below 20mg daily. I used Bactrim DS, 1 tablet bd on two separate days of the week.
I use prednisone 75mg for at least one month, aiming to see a reducing CK level. There is typically a slow recovery from inflammatory myositis if there is significant muscle weakness at baseline. A drop in CK typically occurs well before recovery of muscle strength. I aim to reduce prednisone dose to around 20mg by the end of the third month.
In her case, it took three months for CK to normalise and muscle strength is slowly returning after six months of treatment. AST and ALT both reduced at a similar rate to the drop in CK, confirming the transaminase increase is due to muscle damage. AST and ALT return to normal with ongoing use of methotrexate. It is important to periodically screen for steroid-induced diabetes given the high doses of prednisone used.
There is inevitable muscle fibre necrosis with aggressive myositis such as this case. Muscle strength is gained by hypertrophy of unaffected muscle fibres and thus guided strength rehabilitation is vitally important for a good recovery.
Dr Andrew Jordan is a rheumatologist based in Parramatta, Sydney, with a special interest in inflammatory arthritis, gout and PRP injections
