Clinical Presentation of the Idiopathic Inflammatory Myopathies Clinics Clinics 2002

8/14/2019 Clinical Presentation of the Idiopathic Inflammatory Myopathies Clinics Clinics 2002

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Clinical presentation of the idiopathic

inflammatory myopathies

Yusuf Yazici, MDa,b,*, Lawrence J. Kagen, MDa,c

aHospital for Special Surgery, Weill Medical College of Cornell University, New York, NY, USAb

Long Island College University, Brooklyn, NY, USAcNew York Presbyterian Hospital, New York, NY, USA

The idiopathic inflammatory myopathies (IIM) are a group of disorders that are

characterized by proximal muscle weakness and nonsuppurative inflammation of

skeletal muscle, often accompanied by extramuscular manifestations. Subgroups

of IIM with different presentations include dermatomyositis (DM), polymyositis

(PM), inclusion body myositis (IBM), cancer-associated myositis, overlap syn-

dromes, amyopathic DM, and the antisynthetase syndrome. The frequencies of

signs and symptoms among clinical groups show some statistically significantdifferences and are particularly important in inclusion body myositis, which can

exhibit more atrophy, distal, and peripheral muscle weakness [1]. Patients with

IIM may present in acute, subacute, or insidious ways, and with a variety of non-

specific symptoms including fatigue, malaise, weight loss, myalgias, or arthralgias

that may mimic other disorders and result in unfortunate delays in diagnosis.

Organ systems involved

Cutaneous involvement

Rash

The cutaneous manifestations of DM may be pathognomonic for, character-

istic of, or simply compatible with, DM (Box 1) [2]. The most common rash,

Gottrons papules, is a symmetric, palpable, heaped up appearing, erythem-

atous eruption of the skin overlying the extensor surfaces of the metacarpopha-

langeal and interphalangeal joints of the fingers (Fig. 1). Slight scaling and,

0889-857X/02/$ see front matterD 2002, Elsevier Science (USA). All rights reserved.

PII: S 0 8 8 9 - 8 5 7 X ( 0 2 ) 0 0 0 2 3 - 6

* Corresponding author. Hospital for Special Surgery, Weill Medical College of Cornell Uni-

versity, 535 East 70th Street, New York, NY 10021.

E-mail address: [email protected] (Y. Yazici).

Rheum Dis Clin N Am 28 (2002) 823832


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Box 1. Signs and symptoms of inflammatory myopathies

1. Dermatologic (DM)

A. Rash

1) Periorbital swelling

2) Heliotrope suffusion

3) Gottrons papules

4) V-sign

5) Shawl-sign

B. Periungual telangiectasias

C. Calcinosis1) Usually superficial, rarely deep

2) May be complicated by infection

2. Muscle (DM, PM, inclusion body myositis [IBM])

A. Acute/subacute proximal muscle weakness

B. Usually symmetric but may be asymmetric in IBM

C. Myalgia early in disease course

3. Pulmonary (DM, PM)

A. Fibrosing alveolitis

B. Aspiration

C. Weakness of muscles of respiration

D. Dyspnea

4. Gastrointestinal ([GI], DM)

A. Esophageal dysfunctionB. Gastroparesis

C. Intestinal dysfunction and inflammation

5. Cardiac (PM, DM)

A. Subclinical electrocardiographic findings

B. Rhythm disturbances

C. Congestive heart failure

6. Joints (DM, PM, antisynthetase syndrome)

A. Arthralgia

B. Small joint arthritis

1) Symmetric

2) Nondeforming

Y. Yazici, L.J. Kagen / Rheum Dis Clin N Am 28 (2002) 823832824


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rarely, a thick psoriasiform scale occur and telangiectasia is commonly found

within the lesions. Gottrons papules are considered pathognomonic for DM.The heliotrope rash of DM is violaceous to dusky erythematous, sometimes

with edema, involving the periorbital area and often the upper eyelids, in a sym-

metrical fashion. This rash may be slight and appear as only a mild discoloration

along the eyelid margins. Its presence is highly suggestive of DM; it is rarely seen

in patients with systemic lupus erythematosus (SLE) or scleroderma. Although

it is considered a characteristic skin manifestation of DM, it is not present in all

cases [3].

Other skin findings include a macular erythema over the lower neck and upper

chest in a V distribution anteriorly (V-sign), often accompanied by a more diffuseanterior chest rash (Fig. 2), or in a shawl-like distribution posteriorly and over the

upper, outer, proximal extremities (shawl-sign) (Fig. 3). The scalp and the back of

the neck below the hairline may be involved. Scalp involvement is common and

presents as an erythematous to violaceous psoriasiform dermatitis [2]. Clinical

distinction from psoriasis or seborrheic dermatitis may be difficult and sometimes

histopathologic studies may be helpful in this regard [3]. In addition to these

features, severe erythema of the palms, scaling scalp plaques, and hyperkeratosis

of the palmar and lateral aspects of the fingers (mechanics hands) are commonly

seen. Periungual abnormalities including telangiectasias and cuticular over-growth, and irregular, indurated plaques over the fingers with mucin accumula-

tion in the dermis may also occur in patients with DM.

Less frequently, a papular, or even vesicular rash over flat surfaces has been

observed. Subcutaneous panniculitis, manifested as induration and erythematous

plaques over the torso and extremities may occur [4]. Erosive lesions and

exfoliative erythroderma may also be observed.

Fig. 1. Gottrons papules. Rash of DM with Gottrons papules over bony prominences (proximal

interphalangeal [PIP] and metacarpophalangeal [MCP] joint areas).

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Although the rash is not usually a severe medical problem, dehiscence of the

rash can occur and may be severe. Open lesions of this type on the trunk usuallyconnote a poor prognostic sign.

Histologically, skin biopsies have demonstrated hyperkeratosis, focal epi-

dermal atrophy, liquefaction of the basal level, mucin deposition, dermal edema,

and a mononuclear cell infiltrate composed of CD4+ T cells and macrophages

proximal to small vessels in the dermis. At the dermo epidermal junction and in

Fig. 2. V-sign and anterior chest rash. Rash of DM evident over the anterior thorax as well as over the

upper outer arms.

Fig. 3. Shawl-sign. Rash of DM over the posterior thorax.



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dermal microvessels, IgG and complement components are found. Direct im-

munofluorescence reveals a band of immunoglobulin and complement at the

basement membrane zone [5]. These histologic findings are similar to those ofsubacute cutaneous lupus erythematosus (SCLE).

The skin lesions of DM are photoaggravated in some patients [6]. Other as-

pects of IIM, however, including muscle disease, may also flare after sunlight

exposure. The rash of DM often appears before signs of myopathy become evi-

dent. Dermatologic involvement may be confused with that of SLE or of other

papulosquamous skin disorders and histologically cannot be differentiated from

SLE skin manifestations [3].

CalcinosisSkin calcinosis is a vexing and often disabling complication, most commonly

seen in children or young adults, but also encountered in adult patients, as well.

Hard, yellow-white nodules can arise over bony prominences and often in areas

of repeated trauma. These deposits of calcium may erupt onto the skin surface

and be the site of secondary infections. This may be extremely troublesome, par-

ticularly at the olecranon bursa area. The infections are often caused by Staphy-

lococcus aureus. The deposits, generally several millimeters in diameter, can also

be extremely painful, particularly at the fingertips.

Other patterns of calcification that have been noted, include: (1) deep depositswith linear masses, as well as investments of the fascia of the musculature; and

(2) reticular subcutaneous deposits [11].

Muscle involvement

Most patients present with acute or subacute onset of proximal muscle

weakness that is usually symmetric. Initially, myalgia, which is experienced as

soreness or a Charley horse sensation in the proximal musculature of the upper

and lower extremities, may be present. Myalgia is generally not a limiting featureof these disorders and often disappears as the illness becomes more chronic [7].

Muscular weakness represents the major source of disability faced by patients

with inflammatory myopathies. There is difficulty in raising the head when supine,

lifting, carrying, climbing steps or street curbs, and dressing. Many patients find

they need to use the handrail of stairways as a way of pulling themselves up, as

well as to holding on to other supports to prevent a fall when going down.

Although strength of dorsiflexion of the ankle may be preserved, loss of hip

flexion power may result in tripping over curbs or stumbling on uneven terrain.

Proximal muscles are generally affected to a greater degree; however, withchronicity, increasing severity, and in the case of patients with inclusion body

myositis, distal musculature is also involved. Not all skeletal muscles are equally

involved; facial musculature, innervated by the cranial nerves, is generally spared.

Neck extensors, although involved, are less affected than flexors. Flexors of the

knee are less involved than extensors. Weakness also involves the musculature of

the torso, making arising from the supine position difficult. In order to arise from



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bed the patient may need to roll to the side, and dangle the legs over the edge as a

counterweight while pushing with the arms. Weakness of proximal musculature of

the lower extremities, impairing the ability to arise from a seat, severely limitsindependent function.

Histologically, muscle biopsies in patients with DM demonstrate a mono-

nuclear cell infiltrate, emanating from blood vessels and extending into the

myofibers. Myofiber necrosis and regeneration are seen, and in chronic cases,

replacement of parts of the fascicle with adipose tissue and collagen occurs. The

inflammatory infiltrate is composed mainly of B cells and CD4+ lymphocytes in

perivascular areas. CD8+ lymphocytes may also be present in the endomysium.

Macrophages are encountered in areas of myofiber necrosis, along with poly-

morphonuclear leukocytes. Reduction in the number of capillaries and micro-vessels, and perifascicular atrophy are evidence of the vasculopathy seen in this

disorder. As a part of the inflammatory process, MHC determinants of Class I and

Class II can be demonstrated on myofibers. Adhesion molecules, ICAM-1 and

VCAM-1 are upregulated, as are cytokines TNF a and IL-1 along with other

cytokines and monocyte attractant proteins that serve to attract leukocytes to the

inflammation site [8].

PM is characterized by the same pattern of muscle weakness as DM but

without the rash. Histologic features of muscle are similar with the exception of a

preponderance of CD8+ lymphocytes in the endomysium on immunostaining. Inpatients with PM the risk of associated interstitial pulmonary disease seems to be

higher, but the risk of malignancy is much lower than in patients with DM.

Pulmonary involvement

Respiratory complaints can be prominent and a serious feature in patients with

inflammatory muscle disease. Interstitial lung disease secondary to fibrosing

alveolitis is seen in patients with DM or PM and is associated with esophageal

involvement as well as with the presence of antibodies to aminoacyl-transfer RNA

synthetase [9]. In some patients, chest radiographs or pulmonary function testing

can indicate the presence of intrinsic lung disease in the absence of clinically

apparent signs or symptoms. In others, exertional dyspnea is an indolently

progressive problem. Finally, some patients can present acutely with aggressive

diffuse lung disease, with nonproductive cough, fever, and severe, rapidly prog-

ressive dyspnea.

Exertional dyspnea simulating lung disease can also result from weakness of the

diaphragm and intercostal muscles. Additionally, pharyngeal and esophageal dys-

function may lead to chronic aspiration with concomitant pulmonary involvement.

Pulmonary hypertension is a rare but very worrisome finding in some patients.

It is usually associated with pulmonary fibrosis, and predicts a poor prognosis.

GI involvement

The most common GI symptom is dysphagia, caused by the weakness of the

tongue, pharynx, or esophagus, and disordered esophageal motility [10]. Esoph-



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ageal dysfunction occurs in 15% to 50% of patients and can be associated with

pulmonary involvement as the result of eructation of solids and liquids with con-

comitant aspiration. Symptoms of reflux esophagitis, abdominal pain, andconstipation alternating with diarrhea, may result from GI tract inflammation.

Delay of gastric emptying has been documented in apparently asymptomatic pa-

tients and severe gastroparesis, although rare, may result in postprandial nausea,

vomiting, and malaise and impair adequate nutrition. Vasculitis of the GI system is

a rare event that may be complicated by intestinal bleeding.

Cardiac involvement

Cardiac involvement requiring therapy is uncommon because most involve-ment is subclinical. When cardiomyopathy from myocarditis causes symptoms,

however, the outcome is very poor. Rhythm disturbances, conduction defects,

less commonly congestive heart failure, and rarely, pericarditis, have been ob-

served. The outcome of these patients is much worse when cardiac manifestations

occur in conjunction with pulmonary disease [3].

Joint involvement

DM and PM are systemic disorders and arthralgia can be present in one fourth

of patients. It is generally noted early in the disease and responds to therapy of the

underlying muscle disease. It commonly involves hands, wrists, feet, and ankles

symmetrically and is nondeforming. Morning stiffness is common.

Clinical manifestations in selected subgroups

Cancer-associated myositis

The exact nature of the relationship between malignancy and myositis hascreated continued controversy; however, most authorities agree that there is an

increased incidence of malignancy in myositis patients [12]. The association is

much stronger for DM than PM, especially in the first 5 years after diagnosis of

myositis. The malignancies seen in patients with DM and PM reflect those found

in an age-matched population, except for a possible preponderance of ovarian

cancer. Most experts recommend that patients with DM have an age-and risk-

specific examination for occult malignancy with further evaluation of any

suggestive symptoms or abnormal findings. Older age at onset, and male gender

may be independent predictive factors; interstitial lung disease may be protectivefor malignancy in myositis patients [15].

Amyopathic DM

Some patients with characteristic cutaneous findings of DM have no overt

clinical evidence of muscle disease. This syndrome, also known as DM sine



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myositis, makes up about 10% of all patients with rashes consistent with DM.

Overt muscle weakness may not be demonstrated; however, fatigue may be a

complaint and extensive testing can reveal subtle, subclinical myopathic abnor-malities [14]. Many of these patients go on to develop obvious myopathy after a

delay of several months, and rarely, longer.

Antisynthetase syndrome

This entity occurs most often among women in their middle years and is

characterized by inflammatory myopathy associated with low grade fevers,

interstitial pulmonary infiltration, Raynauds syndrome, mechanics hands, and

arthritis of the small joints of the hands. The hallmark of this disorder is thepresence of antibodies to aminoacyl-tRNA synthetases in the serum of affected

individuals. In some patients, the associated findings of Raynauds syndrome

and pulmonary disease may precede or even overshadow the concurrent pres-

ence of myopathy.

IBM

IBM is an illness much like chronic PM. It usually occurs in older patients,

often men, and patients may have more distal weakness, particularly of themuscle of the forearm and hand. The disease onset is frequently insidious and a

considerable delay of months to years may elapse before recognition of the

disease occurs. In many patients, weakness, initially ascribed to the effects of age,

may delay diagnosis leading to irreparable myofiber loss, with atrophy and

disability prior to presentation. Most patients wirth IBM patients do not have

extramuscular manifestations, but dysphagia is not uncommon.

Histologically, the inflammatory infiltrate is similar to that of PM with the

presence of cytotoxic CD8+ lymphocytes invading the endomysium. Addition-

ally, rimmed or beaded vacuoles, containing eosinophilic inclusions, are presentin the cytoplasm. Eosinophilic inclusions can also be found in the nucleus.

Immunohistology revealed the presence ofb amyloid, ubiquitin, phosphorylated

t protein, B crystalline, and transglutaminases as well as other components

within inclusions [13]. The role of these materials in the pathogenesis of inclusion

body myositis remains to be fully elucidated.

Summary

The hallmark of the inflammatory myopathies is muscle weakness. Although

this feature can lead to significant disability and impairment of activities of daily

living, its initial presentation may not be recognized early. Older individuals, in

particular, may feel that the changes caused by myositis reflect the effects of

aging rather than those of a disease process, and diagnosis, therefore, may be

delayed. This factor has negative impact on the response to therapy. Inclusion



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body myositis, with its insidious onset in older people, and laboratory findings

which may not be markedly abnormal, presents a diagnostic challenge. DM, with

its characteristic symptomatic rash, is generally brought to medical attentionmore quickly.

Another area of diagnostic concern occurs when associated organ involvement

precedes myopathy. This has been observed, for example, with interstitial lung

disease, and again represents a challenge to physicians. In this connection, the

antisynthetase syndrome presenting with fevers, Raynauds features, arthritis, or

pulmonary involvement may not initially be recognized as a manifestation of

inflammatory muscle disease.

Each subgroup of IIM may present with a variety of extramuscular features

that can complicate diagnosis and alter therapy and prognosis. This is particularlytrue for the pulmonary, GI, and cardiac manifestations and when cancer is

associated with myositis. For these reasons, such features of IIM should be

carefully evaluated, treated, and monitored over the course of the illness; in some

cases these may play a greater role in determining the outcome of patients with

IIM than the muscle involvement itself. It is hoped that in the future increased

familiarity with the manifestations of the inflammatory myopathies, together with

a better understanding of the underlying pathogenesis, will lead to more rapid

diagnosis and more effective treatments.

References

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Opin Rheumatol 1998;10:556 61.

[3] Callen JP. Dermatomyositis. Lancet 2000;335:53 7.

[4] Fusade T, Belanyi P, Joly P, et al. Subcutaneous changes in dermatomyositis. B J Dermatol 1993;128:4513.

[5] Vaughan Jones SA, Black MM. The value of direct immunofluorescence as a diagnostic aid in

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Clinical Presentation of the Idiopathic Inflammatory Myopathies Clinics Clinics 2002