Case
A 72 year-old female presented in
June 2015 with rash on her hands, face and around her nostrils. She was
referred to dermatologist, skin biopsy was performed and showed lichen planus,
which was subsequently treated with topical steroids and emollients.
5 months later rash recurred,
spreading to the arms and torso. She developed progressive myalgia affecting
the neck and proximal limb muscles in combination with progressive swallowing difficulty.
Mobility deteriorated such that she started to fall in the community and was
unable to perform activities of daily living independently.
After dermatological review polymyalgia
rheumatic was suspected for which she was started on 20 mg prednisolone.
Despite this, two months later she was unable to stand or sit without
assistance. Further deterioration in swallow resulted in presentation to Whipps
Cross Hospital and subsequent transfer to Royal London Hospital.
Interview revealed no significant
past medical history except for idiopathic thrombocytopaenia and longstanding
osteoarthritis. She was on no regular medication and had no history of alcohol
use or smoking.
On examination she
was short of breath (FVC<0.9) and failed both bedside and formal swallow
assessments. There was a heliotrope rash and Gottron’s papules as well as
erythematous rash on left elbow, torso and behind both ears. There were dry
mucous membranes (eyes and mouth). Weakness was pronounced in the proximal
muscle groups with distal sparing. She was areflexic, sensation was intact.
Investigations
Blood results showed
normal ESR and CRP with increased CK of 900, ANA 1/160 and ENA negative.
MRI head and whole
spine showed increased signal within the neck and paraspinal muscles.
Nerve conduction
studies showed incidental mild left carpal tunnel syndrome, whilst needle EMG
sampling revealed no spontaneous activity in any of the muscles sampled.
However, voluntary activated motor units were markedly polypahsic and
short in duration with evidence of early recruitment.
Muscle MRI showed increased
signal in relation to the musculature of the pelvic girdle and within the thigh musculature
bilaterally, which would support the diagnosis of myositis.
Muscle biopsy showed
widespread upregulation of MHC Class I, fibre necrosis with prominent
macrophagic (and milder lymphocytic) infiltration as well as fibre
regeneration.
Diagnosis
Inflammatory myopathy with
dermatological involvement (Dermatomyositis)
Next steps
The priority was to excluding
underlying malignancy.
CXR, CT CAP and Mammogram were
performed.
CT CAP showed early
bronchiectatic changes in the left lung base but no malignancy. Mammogram
showed a dense, nodular background pattern with scattered benign
calcifications.
PET revealed mildly increased
uptake in the muscles and basal pleural thickening.
An extended ENA panel including HMGCR antibodies were negative. Anti-TIF1 gamma antibody was positive.
Treatment:
The focus of acute
treatment was to control the inflammatory drive leading to muscle damage. As
such we administered 3 days of IV methylprednisolone followed by 60 mg
prednisolone. One week later she was given four days of IV immunoglobulins. She
also received IV cyclophosphamide.
For maintenance
therapy, methotrexate was given with folic acid, PPI cover and bone protection.
Owing to the
swallowing difficulties a radiological guided gastrostomy tube was inserted for
nutritional support.
She was discharged to
an inpatient rehabilitation unit and finally to home.
Outcome:
Since August 2016
there are no further dermatological manifestations and she remains rash
free. There has been ongoing
improvement in her muscle strength such that she is able to rise from a chair
without the use of her arms and is independently mobile. Swallow has improved
such that she is meeting her nutritional needs orally and no longer requires
supplementation via gastrostomy tube.
Unfortunately just 3
months after last clinic review she developed severe and rapidly progressive
abdominal swelling and large bilateral PEs. She has now been diagnosed with
ovarian teratoma, not previously evident on malignancy screen
Learning Points:
1)
Dermatomyositis
is a multisystem disorder.
2)
Early
recognition of myositis and treatment can lead to excellent outcomes
3)
TIF1
Gamma antibody is strongly associated with malignancy. The dermatological and
muscle disease can pre-date malignancy by 2 years or more.
Discussion
Malignancy
Dermatomyositis and
Polymositis are strongly associated with malignant disease, particularly
ovarian, cervix, lung, pancreatic, stomach, colorectal and non-Hodgkin
lymphoma. In both, incidence of malignant disease is highest at time of
myositis diagnosis and for one year afterwards but may arise before, or even
> 5 years after diagnosis.[1]
Predictors for low
risk (ie good prognostic signs) include, interstitial lung disease, Anti-Mi2 or
Antisynthethase. Anti-TIF1-gamma
antibody (like in the case of the patient described), Nuclear matrix protein (NMX), older age and dysphagia are associated with increased risk of malignancy and are thus
poor prognostic signs.
TIF1-gamma
Recently, it has been
revealed that an anti–transcriptional intermediary factor 1 g antibody
(TIF1-g-Ab) is frequently detected in the sera of patients with cancer
associated myositis (CAM).
Because TIF1-g
regulates the tumor growth factor b pathway, it is reported to be related to
tumor growth in some malignancies, and may therefore be involved in the key biological
mechanisms linking cancers and myositis.
Treatment
Despite the lack of
placebo-controlled trials, glucocorticoids are considered the mainstay of
initial treatment for idiopathic inflammatory myopathy and myositis-associated
interstitial lung disease.
First-line conventional immunosuppressive drugs include either
methotrexate or azathioprine, and when they fail, more aggressive therapy
includes mycophenolate mofetil, tacrolimus or cyclosporine, intravenous
immunoglobulin, rituximab, or cyclophosphamide.[2]
IVIg demonstrated efficacy in DM
in a double-blind, controlled trial in 15 patients with refractory DM. In
another prospective open-label trial with 35 patients with PM, treatment with
IVIg was associated with a significant clinical improvement in 70% of the
patients, with stable efficacy reported in half of the patients, 3 years after
stopping IVIg. [3]
IM is a multisystem
disorder and concern should be given to extramuscular aspects of the disease,
particularly the potential for respiratory and cardiac involvement.
Also of relevance is
the occurrence of other complicating issues: pain, fatigue, dysphagia and
depression.
[1] Chinoy et al. The
diagnostic utility of myositis autoantibody testing for predicting the risk of
cancer-associated myositis. Ann Rheum Dis 2007; 66 (10):1345
[2] Siamak Moghadam-Kia,
Rohit Aggarwal, and Chester V Oddis. Treatment of inflammatory myopathy:
emerging therapies and therapeutic targets. Expert Rev Clin Immunol. 2015;
11(11): 1265–1275.
[3] Dalakas MC, Illa I,
Dambrosia JM, et al. A controlled trial of high-dose intravenous immune
globulin infusions as treatment for dermatomyositis. N Engl J Med.
1993;329(27):1993–2000
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