Page 793 - Clinical Immunology_ Principles and Practice ( PDFDrive )

764 Part SIX Systemic Immune Diseases

with immunosuppressive agents. 34,35 Patients with limb-girdle
Corticosteroids muscular dystrophies may mimic PM clinically. They may have
Corticosteroids are the main immunosuppressive agents used inflammation on muscle biopsy and may occasionally have
in myositis treatment. An initial course of pulses of methyl- associated autoantibodies. Thus patients with a suspected IIM
prednisolone may be helpful, particularly in disease of acute who do not respond to immunosuppressive therapy should
onset, and may also be helpful in managing disease flares. If undergo further evaluation, including genetic testing, to search
active muscle inflammation persists or the side effects of for a limb-girdle muscular dystrophy.
corticosteroids are severe, other immunosuppressive treatments
are employed. Nonskeletal Muscle Involvement
Other organs frequently involved in myositis include the skin,
Second-Line and Third-Line lungs, and joints. Such organ involvement and the systemic
Immunosuppressive Therapies features of myositis (fever and weight loss) usually improve with
The most frequently used second-line agents in the treatment immunosuppressive therapy that controls inflammation in the
of myositis are azathioprine and methotrexate. Azathioprine skeletal muscle. Hydroxychloroquine and other antimalarials are
reduces long-term disability. Methotrexate is useful in patients useful in controlling the rashes associated with myositis.
with little or no response to corticosteroid therapy. Combination
therapies, such as methotrexate with azathioprine, are useful DIAGNOSTIC TOOLS, EVALUATION, AND
even if patients have failed to respond to one of the agents alone. DIFFERENTIAL DIAGNOSIS
High-dose intravenous immunoglobulin (IVIG) is of proven
25
benefit in DM. Whereas patients with statin-associated anti-
26
HMGCR myopathy may be particularly responsive to IVIG, CLINICaL PEarLS
its usefulness in PM is less predictable. Apheresis proved ineffective
27
in a controlled blinded study. Both cyclosporine and tacrolimus Clinical Features That Suggest a Non-Idiopathic
have been effective in some cases, as have cyclophosphamide Inflammatory Myopathy Diagnosis
and chlorambucil. The most recent therapeutic options include
mycophenolate and rituximab. Recently a large randomized • Family history of a similar illness
• Weakness related to exercise, eating, or fasting
placebo-phase clinical trial was conducted to elucidate the role • Sensory, reflex, or other neurological signs
of a 44-week course of rituximab therapy in adults and children • Cranial nerve involvement
with refractory PM and DM. In general, 83% of refractory myositis • Fasciculations
patients met the Definition of Improvement (DOI), and the • Muscle cramping (severe)
presence of antisynthetase and anti–Mi-2 autoantibodies was • Myasthenia (increasing weakness with repeated contractions)
associated with a shorter time to improvement. 28,29 In refractory • Myotonia (difficulty relaxing a contracted muscle)
• Significant atrophy or hypertrophy early in the illness
patients who have not responded to the above-mentioned treat- • Marked asymmetry
ments, biological agents such as etanercept, adalimumab, anakinra, • Dyspnea due to diaphragmatic weakness with normal chest x-ray
abatacept, and high-dose cyclophosphamide have been tried with
variable success. 16,30–33 Thus far, there has been no effective
therapeutic regimen for IBM. However, IVIG has been reported Clinical, laboratory, pathological, and electrodiagnostic findings
to provide a transient response. 13 contribute to the proper diagnosis of IIM. Even in individuals
with typical clinical features, it is essential to exclude other diseases
Monitoring Disease Activity that may have similar symptoms and signs (Table 56.6). Certain
Improvement in strength and normalization of serum CK activity clinical features should suggest a different diagnosis. These include
are the best indirect measures of disease activity. A decrease in a family history of a similar illness; sensory, reflex, or other
serum CK activity may herald clinical improvement, but cortico- neurological changes; fasciculations; a relationship of the weakness
steroid treatment alone can reduce CK activity without associated to exercise, food intake, or fasting; major muscle cramping,
clinical improvement. A lack of improvement in strength in a myotonia (difficulty relaxing a contracted muscle), or myasthenia
corticosteroid-treated patient may be due to the resistance of the (increasing weakness with repeated contractions); significant
inflammatory process, the presence of a corticosteroid-induced early muscle atrophy or hypertrophy; marked asymmetry; weak-
myopathy, muscle atrophy, and/or misdiagnosis. A diagnostic and ness in the distribution of the cranial nerves; and dyspnea due
therapeutic taper of the corticosteroids may then be warranted. If to diaphragmatic weakness rather than lung fibrosis.
inflammation is present concurrently, other immunosuppressive The single most useful laboratory feature of muscle destruction
agents are useful as the dosage of corticosteroids is lowered. If is elevation of the serum CK, although this is nonspecific, and
the CK value begins to rise, even if it is still within the normal a small proportion of patients—probably <5%—have a bonafide
range, and the symptoms of myositis are worsening in a patient inflammatory muscle disease without ever having an elevated
whose disease has previously been controlled with corticosteroids, CK. Elevations of the serum levels of aldolase, serum glutamic-
an increase in the dose may be warranted. oxaloacetic transaminase (SGOT), serum glutamate pyruvate
transaminase (SGPT), and lactate dehydrogenase (LDH) are as
Treatment-Resistant Myositis frequent but less specific for muscle disease. Unlike inflammatory
Some treatment-resistant PM patients have another disease. In markers for other autoimmune inflammatory diseases, those
such cases IBM or a liED-girdle muscular dystrophy should be such as the erythrocyte sedimentation rate (ESR) and C-reactive
suspected. Unlike other myositis patients, those with IBM rarely, protein are often not elevated. Although some studies have shown
if ever, improve in strength with immunosuppressive therapy, ESR to be elevated in 50% of patients, most experts find a
but stabilization of strength can be achieved in some IBM patients substantially lower proportion of IIM patients to have an elevated