Myositis

Question 1

Definition

Answer 1

Inflammatory myopathies, collectively named myositis, are a group of systemic autoimmune inflammatory diseases that involve an inflammatory mononuclear cell infiltrates in muscle tissue and share the clinical features of slowly progressive, symmetric muscle weakness, and fatigue.

Question 2

Chronic, idiopathic, inflammatory myopathies can occur as

Answer 2

1 . isolated inflammatory muscle disorders
2 . be associated with another defined connective tissue disease such as Sjögren’s syndrome, systemic sclerosis, mixed connective tissue disease, SLE or RA.

Question 3

Inflammatory myopathies can be subclassified into 3 major groups

Answer 3

1. Polymyositis (PM) - involves mainly inflammation and damage to many muscles. In PM the skin is not involved!!  no malar rash, no Gottron lesions and no heliotrope rash around the eyelids (soon to be discussed).
2. Dermatomyositis (DM) - involves inflammation of the muscles AND skin diseases.
3. Inclusion body myositis (IBM) - inflammation of the muscles that is characterized by accumulations of abnormal inclusions of misfolded protein. Manifesting similarly to polymyositis.
4. Immune mediated necrotizing myositis (IMNM) – related to the use of statins

Question 4

• Some cases of dermatomyositis are associated with

Answer 4

carcinoma (especially gastric carcinoma)

For this reason, if a patient presents with a dermatomyositis, we need to consider screening them for cancer. This increased risk is both at the time of DM diagnosis but also after more than 10 years

Question 5

• Inclusion body myositis responds poorly to

Answer 5

corticosteroids and immunosuppressants, which is an important clinical clue to differentiate between polymyositis and IBM.

Question 6

Polymyositis and Dermatomyositis

Epidemiology

Answer 6

• Incidence rate of idiopathic inflammatory myositis is 2-7 per 1 million inhabitants.
• More frequent in women than in men (F:M 3:1).
• The peak of incidence 50-60-year-old people, although they may start at any age.
• The ratio between PM and DM correlates directly with UV-light irradiation.

Question 7

Etiology

Answer 7

Autoimmune diseases

• Genetic factors:
  o In Caucasians the strongest association is to HLA DRB10301 and DQA10501, whereas in Asians the strongest associations are to HLAB7.
   This information is not used much in clinical practice (unlike spondyloarthritis).
  o Non-HLA genes polymorphism in gene of proinflammatory cytokines (-308TNFA genotype).
• Environmental factors
  o Infections can trigger the disease - e.g some acute and self-llimiting forms of myositis have been reported with coxsackie, echo and influenza viral infections, mainly in children, but their role in chronic myositis is uncertain. Unlike other conditions, there isn’t one specific virus associated with this disease.
  o UV-light exposure - mainly as a precipitating factor for the skin manifestations in dermatomyositis.

Question 8

Skeletal muscles manifestations  chief manifestation

• Proximal muscle symmetrical weakness

Answer 8

usually in the muscles of the shoulder and pelvic girdle, proximal limbs and neck muscles- this weakness will be typically described as difficulty in combing the hair (so lifting the arms), climbing the stairs, cross legs, lift the head from the pillow, getting up from the chairs and the bed, crouch cross legs, waking, swallow, nasal voice and dysphagia.
a. Distal involvement can develop late in disease.
b. Inclusion body myositis might present with a distal and asymmetric muscle weakness, particularly of the muscles of the forearm and hand resulting in finger flexor weakness.

Question 9

• In aggressive forms of the disease:

Answer 9

pharyngeal muscles, esophageal and respiratory might be involved.

Question 10

a. In PM/DM dysphagia

Answer 10

IS NOT RARE, usually the upper type

The cricopharyngeal muscle is a sphincter with circular fibers, which in normal conditions is in a tonic state. Only during swallowing is this tonic state inhibited for a very short time. Disruption of the relaxation phase is referred to as achalasia.

Inflammation and oedema during myositis may inhibit relaxation and cause weakness of this muscle with resulting dysphagia.

Question 11

Detection of cricopharyngeal achalasia in myositis is important:

Answer 11

i. Due to an increased risk of aspiration pneumonia
ii. Myotomy may lead to a rapid improvement of the patient’s condition

Question 12

• The muscles of the eye are never involved
• At the early stage of the disease the muscle involves pain (like stiff muscles after a workout)- this is due to enzymes releases that cause muscles breakdown

Question 13

Skin manifestations:

The cutaneous manifestations of DM may be mild or severe and may in some cases dominate the clinical symptoms. 3 key skin changes:

Answer 13

1. Rash with a purple discoloration (called ‘heliotrope rash’) of the upper eyelids.

It might be associated with the presence of peri-orbital edema. Red or violaceous erythemas may also be located over the shoulders, neck and chest (e.g. shawl rash). The rash frequently face and chest in the shape of V. Depigmentation on the chest occurs after some time during the course of illness. Other locations the lateral thigh (called Holster sign’) and lower back.

Question 14

Heliotrope rash, periorbital edema

Answer 14

This is a typical rash on the upper and lower eyelids, often together with edema of the soft tissue around eyes.

The heliotrope is a plant genus Heliotropium. Heliotrope color varies from bright purple to a deep purple red. This color is observed in the periorbital of patients with dermatomyositis

Question 15

Malar rash

Answer 15

NOT ONLY IN SLE

Question 16

3. Gottron‘s changes

Answer 16

(the most specific skin manifestation) are erythematous to violaceous papules and plaques (Gottron’s papules), or macules (Gottron’s sign), over extensor surfaces of joints, especially elbows, knuckles, and knees, generally in a symmetric distribution.

Question 17

The skin rash may precede

Answer 17

the muscle symptoms by months or even years and in some patients the skin manifestations may be the only clinical sign of DM, often named amyopathic dermatomyositis or dermatomyositis sine myositisthe muscle symptoms by months or even years and in some patients the skin manifestations may be the only clinical sign of DM, often named amyopathic dermatomyositis or dermatomyositis sine myositis

Question 18

The cutaneous manifestations may fail to respond to

Answer 18

immunosuppressive treatment despite improvement of muscle symptoms. Thus, it is possible that different molecular pathways or disease mechanisms cause the skin rash and the muscle inflammation

Question 19

Involvement of the fingers:

Answer 19

1. Mechanic’s hands: hyperkeratosis with frequent fissuring along the lateral and palmar aspects of the fingers.
2. Periungual erythema, nail-fold telangiectasias and cuticular overgrowth. These are the result of alteration in the periungual capillaries that can be seen by a capillaroscopy. However, note that these alterations ARE NOT THE SAME AS THOSE SEEN IN SYSTEMIC SCLEROSIS; while SS involves dilatations of capillary loops, with loss of structure of the surrounding loops, DM involves the loss of homogeneous distribution and enlarged “giant” capillary loops.

Question 20

Subcutenous calcifications

Answer 20

are more common in juvenile dermatomyositis than in adults. Calcinosis predominantly occurs on sites that are subject to friction such as the dorsal side of the elbows and may be localized to the skin, subcutaneous fat, fascia and muscle. It is a difficult condition to treat

Question 21

There are no specific ….

Answer 21

histopathological skin features for dermatomyositis as most features found are also seen in patients with SLE, thus skin biopsy is rarely helpful to distinguish between these two disorders. Skin rash may be precipitated by UV light exposure

Question 22

Lung manifestations:

Answer 22

Dyspnea and cough are common symptoms in patients with PM/DM and interstitial lung disease (ILD) was found in 60-70 % at time of diagnosis.

!These are life threatening involving a progressive destruction of the lung (usually slow but can be also accelerated).

ILD may even be asymptomatic and detected by high resolution computerized tomography (HRCT) and pulmonary function tests. ILD in myositis is not different from idiopathic ILD and is often slowly progressive but occasionally an acute onset life threatening form.

Question 23

major factor causing morbidity and mortality in myositis!

Answer 23

Pulmonary complications !!!!

Question 24

Anti-synthetase syndrome:

Answer 24

Anti-synthetase syndrome is a set of symptoms that typically occur for patients who have myositis together with one of several specific autoantibodies known as anti-synthetase antibodies.

Question 25

There are 8 anti-synthetase antibodies that have been identified so far in myositis diseases

Answer 25

By far the most common of these is anti-Jo-1 (from the family of ENA) directed against histidyl-tRNA synthetase, present in approximately 20% of patients with PM/DM

Other anti-tRNA synthetase (anti-PL-7, anti-PL-12, anti-KS, anti-OJ, anti-EJ, anti-Zo) have been found in myositis patients

Question 26

Characteristic clinical features of the syndrome:

Answer 26

• Myositis
• Interstitial lung disease
• Raynaud’s phenomenon
• Non-erosive symmetric polyarthritis in small joints
• Mechanic’s hands

Question 27

Joint involvement

Answer 27

Arthralgia and arthritis which is usually non-erosive are common in myositis patients.

The arthritis mainly affects small joints in the hands and feet.

In particular, arthritis is common in patients with anti-Jo1 and other anti-synthetase. The arthritis is rarely a major clinical problem.

Question 28

Heart

Answer 28

Cardiovascular disease is a major risk factor for death among myositis patients.

The most frequently reported clinically overt manifestations are congestive heart failure, and conduction abnormalities.

Question 29

Inclusion Body myositis

Answer 29

It has an insidious onset of muscle weakness over months to years. It presents with distal and asymmetric muscle weakness, particularly of the muscles of the forearm and hand resulting in finger flexor weakness

Question 30

Epidemiology

Answer 30

• The prevalence is estimated to 4-9:1,000,000
• Males affected more than females
• Age of onset usually greater than 50

Question 31

Autoantibodies are present in 70%:

Answer 31

anti-cytosolic 5ʹ nucleotidase 1A (cN-1A).

Question 32

IBM may be associated with another inflammatory connective tissue disease.

Question 33

What helps distinguish IBM from PM

Answer 33

PM is the presence of rimmed vacuoles and cytoplasmic inclusions within muscle fibers; however, these are not demonstrated in 20 to 30% of any given IBM muscle biopsies.
IBM responds poorly to corticosteroids and immunosuppressants.

Question 34

Characteristic distribution of weakness and atrophy in inclusion body myositis.

Answer 34

(a) Quadriceps atrophy. (b) Asymmetric atrophy of flexor muscles in the forearm, with asymmetric weakness of the deep finger flexors.