White : Diseases of the Skin - Collagen Vascular Diseases

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Gary M. White & Neil H. Cox

Diseases of the Skin

13	Collagen Vascular Disease

DERMATOMYOSITIS

Etiology and pathogenesis

Dermatomyositis is an inflammatory eruption of the skin associated with myositis. It overlaps with polymyositis without skin involvement, but conversely may occur as an ‘amyopathic’ form with characteristic rash but no myositis. The skin changes most commonly precede or accompany the myositis.
About 25% of cases are paraneoplastic, mostly in patients aged over 40 years. A small proportion of cases are overtly autoimmune, being associated with other disorders such as LE, and many other ‘idiopathic’ cases will have some detectable autoantibodies (Table 13.7). Antibodies to various tRNA synthetases are infrequent but relatively speciﬁc, and correlate with clinical features such as fever, lung involvement, and polyarthropathy. A positive ANA is found in about 50% of patients.

Table 13.7 AUTOANTIBODIES IN DERMATOMYOSITIS

Category	Antibodies	Comments
Myositis- speciﬁc antibodies (MSA)	Cytoplasmic: anti-aminoacyl tRNA synthetases (e.g. Jo1, PL7, PL12), anti-tRNA, anti-SRP Nuclear: Mi2	Antisynthetase and anti- tRNA antibodies are associated with the ‘antisynthetase syndrome’, which includes mechanic’s hands, myositis,arthritis, Raynaud phenomenon, and interstitial lung disease. They can be positive in lupus erythematosus and in Sjögren syndrome. Anti-SRP is associated with polymyositis and poor response to treatment. Anti-Mi2 is associated with good prognosis dermatomyositis, and occurs in up to 20%. Anti-p155 and anti-Se have recently been linked with amyopathic disease. Anti- U1RNP is usually positive in mixed connective tissue disease, and may be positive in several lupus erythematosus variants. Anti-Pm-Scl is positive in some sclerodermas.
Myositis- associated antibodies (MAA	Anti-U1RNP, anti-Pm-Scl	Anti-U1RNP is usually positive in mixed connective tissue disease, and may be positive in several lupus erythematosus variants. Anti- Scl is positive in some sclerodermas.
Other autoantibodies that maybe positive in patients with dermatomyositis	Tissue-speciﬁc autoantibodies:antimuscle antibodies, anti-endothelial cell antibodies. Antibodies associated with autoimmune diseases: antinuclear antibody (ANA), antiphospholipid, antihistone

tRNA, transfer RNA; SRP, signal recognition particle.

Childhood dermatomyositis has several features that are uncommon in the adult variant, and may therefore have a different etiology; vasculitic lesions and cutaneous calcinosis are more common (and are now known to be associated with the presence of the tumor necrosis factor-a 308A allele), and gingival telangiectasia is often present.

Drug triggers of dermatomyositis or a dermatomyositis-like rash include hydroxyurea (skin features only), penicillin, sulfonamides, hydroxymethylglutaryl-CoA reductase inhibitors, and interferon-alpha.

Clinical features, diagnosis, and investigations

The rash of dermatomyositis is typically purplish and often has a streaky pattern, which may appear flagellate or zebra-striped. Notably affected body sites (Figs 13.60 – 13.68) are as follows:

•	Around the eyes, with eyelid edema (heliotrope rash)—this may be an early (sometimes the only) feature.
•	Dorsum of the hands, where it may produce streaks along the ﬁngers (Gottron sign, also over knees and elbows) or may be accentuated over bony prominences (Gottron’s papules).
•	Upper trunk, where a V-of-neck photosensitivity distribution (V sign) or upper-back (shawl sign) may be apparent.
•	Knees and elbows—underestimated sites that may cause diagnostic confusion (Fig. 13.67).
•	Nail folds—telangiectasia of nail folds is a prominent feature, with ‘giant’ capillary loops being readily visible, and the cuticles are elongated and ragged.
•	Scalp—itch and scaling are common, sometimes severe, and often not adequately considered.

Fig. 13.60 Eyelid edema may be an early and dramatic sign in dermatomyositis. It may mimic angioedema and contact allergies, but is less variable from day to day. Nail fold changes may be present even if the rash has not evolved at other cutaneous sites.

Fig. 13.61 Dermatomyositis on the dorsum of the hands. A pattern of longitudinal purplish-colored stripes is common (Gottron sign).

Fig. 13.62 (a,b) Dermatomyositis showing the violaceous heliotrope rash, in these cases predominantly affecting the upper eyelid. Heliotropes are a type of plant with purplish-colored flowers. (Panel b courtesy of Dr. G. Dawn.)

Fig. 13.63 Close-up of Gottron papules over the interphalangeal joints of the ?ngers in a patient with dermatomyositis.

Fig. 13.64 A photodistributed pattern of dermatomyositis in a patient without evidence of malignancy. Photoaggravation is relatively common, but rarely as limited to sun-exposed skin as in this case.

Fig. 13.65 Poikilodermatous change on the thumb in a patient with dermatomyositis. The white sclerotic areas are reminiscent of scleroderma disorders.

Fig. 13.66 A streaky or ‘flagellate’ pattern of purplish or violaceous lesions on the trunk is strongly suggestive of dermatomyositis. In this case, there was an underlying non-Hodgkin lymphoma.

Fig. 13.67 Rash on the elbow in a patient with dermatomyositis; the frequency of this is often underestimated, but it is important in differential diagnosis terms, as it often closely resembles the distribution (the knees are also affected) and the plaque morphology of psoriasis.

Fig. 13.68 Mechanic’s hands pattern of dermatomyositis, in a patient with associated interstitial lung disease. There is an appearance similar to chronic hand dermatitis, but with prominence of thickening over the ?nger joints.

Some patients have prominent poikilodermatous or scleroderma-like white areas within the rash, vasculitic lesions may occur (especially in children), and extensive subcutaneous calciﬁcation may be a feature of childhood dermatomyositis (Fig.13.69). True photosensitivity may occur. Mechanic’s hands, a pattern associated with antisynthetase antibodies, consist of ﬁssuring, redness, and scaling, resembling a contact dermatitis (Fig.13.68). Itch is a common, and sometimes dominant, feature of the rash. Occasionally, the facial rash may affect the nasolabial folds and resemble seborrheic dermatitis.

Fig. 13.69 Radiograph showing subcutaneous calci?cation in dermatomyositis. This is a particular feature of the childhood variant of this disorder.

A small number of patients may have typical rash without ever having muscle symptoms, a situation known as ‘dermatomyositis sine myositis’ or ‘amyopathic dermatomyositis’. This latter group may have a higher frequency of photosensitivity and associated autoimmune disease, and possibly have a lower risk of associated malignancy (discussed later), although this may be an artifact of analysis, as they constitute a minority of patients. It has been suggested that this diagnosis can be made with reasonable certainty only if the absence of muscle involvement continues for 2 years after diagnosis of the cutaneous rash, as some patients may have subtle or absent muscle disease for a period after presentation.
The muscle disease is symmetric and predominantly affects proximal muscle girdles. Difﬁculties in brushing hair, or in standing from a sitting position, are typical symptoms. The myositis is diagnosed on the basis of history, elevated muscle enzymes (creatine phosphokinase, aldolase, myoglobin, and urinary creatine:creatinine ratio), electromyography, and, if required, muscle biopsy. Less speciﬁc but often abnormal tests include the ESR. Autoantibody tests such as Jo-1 are also useful if positive.

Association with internal malignancy, and investigations

About 25% of patients with dermatomyositis have an underlying malignancy, with approximately equal proportions diagnosed before, after, and at the time of the skin eruption. Several studies have demonstrated that simple screening tests are adequate to identify the vast majority of malignancies, provided that any abnormal features in the history, examination, or simple tests are pursued. However, these conclusions predated ready availability of computed tomography (CT) or magnetic resonance imaging (MRI) scanning, and it is uncertain to what extent these tests may be important in early detection of asymptomatic tumors: CT of chest, abdomen, and pelvis is increasingly performed in patients with dermatomyositis. Ovarian tumors, in particular, appear to be difﬁcult to detect but are signiﬁcantly linked with dermatomyositis. Bronchial (Fig.13.70), colonic, and breast carcinomas are the most frequently associated tumors in patients with dermatomyositis, essentially reflecting their frequency in the general population; in South-East Asia, nasopharyngeal carcinoma is an important association.

Fig. 13.70 Malignant disease is present in about 25% of cases of adult dermatomyositis. The most frequent neoplasm in men is bronchial carcinoma.

A suggested approach to patients with probable dermatomyositis is shown in Table 13.8.

Table 13.8 INVESTIGATIONS IN DERMATOMYOSITIS

Investigation

Reasons and comments

Thorough history and examination

Skin biopsy

Appropriate autoantibody screen

‘Routine’ blood tests

Malignancy evaluation; baseline for systemic therapy (complete blood count, chemistry, sedimentation rate, glucose)

Malignancy evaluation

Symptoms due to the disease; malignancy evaluation; possible drug triggers; include breast, rectal, and pelvic examination

To exclude cutaneous differential diagnoses, see bulleted list in Differential diagnosis section

To evaluate likelihood of autoimmune collagen vascular disease etiology and overlap syndromes; speciﬁc antibodies, if respiratory symptoms

Malignancy evaluation; baseline for systemic therapy (complete blood count, chemistry, sedimentation rate, glucose)

To detect or monitor muscle involvement

History and bloods as above, plus chest radiograph, stool for occult blood, abdominal and pelvic imaging (at least ultrasound, but increasingly computed tomography or magnetic resonance imaging)

Differential diagnosis

This may include the following.

•	Systemic lupus erythematosus—photosensitive pattern, nail fold changes, malaise, and arthralgia.
•	Scleroderma and overlap diseases—rash of dermatomyositis may have sclerodermatous areas and nail fold changes.
•	Psoriasis—especially if rash is prominent on hands, knees, or elbows.
•	Photodermatoses—especially drug-related and photosensitivity dermatitis.
•	Drug eruptions—especially hydroxyurea, which may produce a rash that mimics dermatomyositis.
•	Dermatitis—mainly if prominent on the face (atopic; seborrheic; contact, especially reactions to eyedrops); also, contact dermatitis is in the differential of the mechanic’s hands pattern.
•	Graft-versus-host disease—may resemble dermatomyositis.
•	Trichinosis—may present as myalgia with periorbital edema.
•	Mycosis fungoides—poikilodermatous rash may resemble dermatomyositis.

Treatment

If there is an underlying malignancy, this should be treated, as usually the disease remits after curative surgery. Additionally, patients who respond poorly to treatment or relapse should be reinvestigated for this possibility.
Patients with amyopathic dermatomyositis may be treated with topical corticosteroids and oral antihistamine, and hydroxychloroquine can be useful in those with photosensitivity.
Most commonly, myositis determines the need for systemic therapy, which is usually with systemic corticosteroids and immunosuppressive agents such as azathioprine, methotrexate (especially in adults), or cyclophosphamide (especially in children). Ciclosporin has also been used recently, and appears to be particularly useful in children. Intravenous gamma-globulin has been used, with good results in a few cases.
Myositis in dermatomyosis may require urgent treatment, as it may affect respiratory muscles, leading to respiratory failure, or may cause dysphagia and a risk of aspiration pneumonia due to pharyngeal myositis. Note that respiratory symptoms due to muscle disease need to be distinguished from the interstitial lung disease that may also occur, or from symptoms due to an underlying bronchial carcinoma or metastases in some patients.

PRACTICE POINTS

•	Do not forget ovarian carcinoma as a cause of dermatomyositis; it may be difficult to detect.
•	Beware of delayed development or deterioration of myositis.
•	Lung disease in dermatomyositis may be directly or indirectly due to muscle disease, may be due to an underlying neoplasm, or may be due to interstitial lung disease.
•	Repeat investigations for malignancy if symptoms alter.