Dermatomyositis (overview) M33.-

Author: Prof. Dr. med. Peter Altmeyer

Co-Autors: Johannes Fritz, Lea Kiefer

Our authors

Last updated on: 29.10.2020

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Synonym(s)

Acute cases; acute parenchymatous; Dermatomucomyositis; imflammatory myopathies; Muscle inflammation; Muscle inflammation acute; Myositis; Myositis acute parenchymatous; Myositis universalis acuta infectiosa; Polymyositis; Pseudo-Trichinosis (Hepp); Purple Disease; Purple disease white spotted; Purple sickness; Wagner(-Unverricht)-Syndrome; white stained (Glanzmann)

History
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Wagner, 1863; Unverricht, 1887

Definition
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Rare, acquired, systemic, antibody or immunocomplex-mediated group of autoimmune diseases with immunological responses against vascular and muscle fibre proteins and diagnostically path-breaking inflammatory skin symptoms. Furthermore, there are inflammatory atrophying vascular connective tissue reactions as well as segmental necroses of the striated musculature, which manifest themselves in a clinically usually clearly prominent muscle weakness.

Like other autoimmune myositides, dermatomyositis can also occur as overlap syndromes with further "collagenoses" and in association with malignant tumors as paraneoplastic syndrome ( dermatomyositis, malignoma-associated).

Classification
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Clinically are distinguished (with frequencies):

Occurrence/Epidemiology
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  • Incidence (juvenile dermatomyositis): 0.2/100,000 inhabitants/year.
  • Incidence (adult dermatomyositis): 0.6-1.0/100,000 inhabitants/year.
  • African-Americans are more frequently affected than Caucasians.

Etiopathogenesis
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Together with polymyositis and inclusion body myositis, dermatomyositis belongs to the group of inflammatory myopathies. Environmental factors, especially sun exposure, can lead to exacerbation of dermatomyositis.

  • Genetic predispositions
    • exist for all idiopathic myositides for the haplotypes HLA-B8, HLA DRB 03; HLA-A68 and HLA-DR3 for classical and juvenile dermatomyositis. In drug-associated dermatomyositis the haplotypes HLA-B 08 and HLA-DR4 were detected. No HLA associations are known for amyoplastic dermatomyositis.
  • Infections:
    • Etiologically significant is the formation of antibodies against muscle antigens (AK against the nuclear Mi-2 antigen, antisynthetase-AK). Viral infections ( picornaviruses or Coxsackieviruses) are discussed as a trigger mechanism. Antibodies against viral surface antigen genes may have structural similarity to nuclear antigens and induce antibody formation. In children, bacterial focal events can also cause antibody formation.
  • A humoral immune mechanism is described:
    • This leads to the deposition of C5b-9 complement complexes on the endothelium of the skin and skeletal muscles. For polymyositis as well as for dermatomyositis there is an increased frequency of haplotypes with DR3 with up to 75%. Dermatomyositis symptoms have been observed in congenital immunodeficiencies ("X-linked immunodeficency") as well as in AIDS and HTLV-1 associated T-cell lymphomas (see below lymphoma, cutaneous T-cell lymphoma).
  • Drugs:
  • Dermatomyositis as cutaneous paraneoplasia:
    • in 18-32% of patients; mostly patients > 50 years): clustering in individual families. The relative risk of developing malignancies is 2.4 to 3.8 times higher than in the average population. The risk of tumour development is highest in the first year of diagnosis and decreases continuously in the following years. The most common tumours are ovarian carcinomas, gastrointestinal carcinomas, lung and breast carcinomas, prostate carcinomas and non-Hodgkin's lymphomas. In Asians, nasopharyngeal carcinomas are the most common. In juvenile dermatomyositis, the tumour association is missing.

Manifestation
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  • In the adult form there is gynecotropia: women are affected about 1.5-2 times more often than men. In adult dermatomyositis there are 2 peaks in frequency, 35-44 LJ and 55-60 LJ.
  • No sex preference in childhood (this statement is not found in other studies, here: F:M=6:1). First manifestation of juvenile dermatomyositis: Mostly 7-8th LJ.

Clinical features
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Accommodation/General: General fatigue with muscle weakness and sore muscles. Patients can only perform their normal activities (e.g. climbing stairs, combing their hair) with difficulty or not at all.

Note: The patient appears tired during the consultation, leans on the chair when getting up, the hands are closed, the gait is sluggish, the voice is soft to broken.

Integument (often the first sign of dermatomyositis: skin symptoms precede muscle weakness in 1/3 of cases).

Initial stage: Initially flat facial swellings with conspicuous eyelid edema, heliotropic, red to blue-violet, areactive but also itching or painful erythema and/or plaques which appear butterfly-shaped over the cheeks, leaving a perioral zone free and affecting the neckline heliotropically. More rare are blurred, flat, deep red erythema on the back. The following phenomena are described in detail:

  • Gottron's sign: Of diagnostic significance are deep red, streaky erythema and papules on the sides of the fingers (= Gottron's sign in about 70% of patients).
  • Nail fold hyperkeratosis: (the attempt to push back the nail fold is very painful = Keining sign) with mega and tuft capillaries, extended and torqued capillaries possibly with bleeding (capillary microscopy).
  • Heliotropic erythema:wine-red, diffuse erythema is particularly visible in sun-exposed skin areas (face, eyelids, décolleté).
  • Perioral pallor: characteristic of this condition is the absence of erythema in the perioral region (this makes the perioral region appear pale: perioral pallor).
  • V-sign: confluent macular erythema spread in a V-shape over the lower anterior neck and upper chest (symptoms are often associated with the anti-Mi-2 autoantibody)
  • Shawl sign: confluent flat erythema localized like a scarf.
  • Holster sign: red or red-violet flat erythema, limited to the lateral thighs or hips in form of a worn holster.

Late stage: Colorful (poikilodermatic) skin due to brown-red discoloration of the foci with sunken atrophic areas, sometimes also coarse sclerotic plaques with calcification processes (especially in children and adolescents). The skin lesions are often combined with a diffuse effluvium .

  • Mechanic hands: hyperkeratotic cracked skin on the palmar and lateral side of the fingers.

Muscles: Increasing, symmetrical, painful (sore) muscular weakness, particularly in the proximal parts of the limbs. Calcification of the muscles is possible, in adults rather rare, in children and adolescents up to 40% (see below dermatomyositis, juvenile).

Skeletal system: About 25% of patients with inflammatory muscular diseases suffer from arthralgia and arthritis. Partly type of symmetrical polyarthritis, also known as oligo- or monarthritis. Rarely mutating arthritis (DD: antisynthetase syndrome; see below overlap syndrome). Also: Severe osteoporosis, more extensive calcification of soft tissues (tendons, muscles, aponeuroses) as well as considerable joint deformities (joint space remains!).

Lung: Lung involvement (primarily interstitial pneumonitis) in 15-30% of patients.

Vessels: An accompanying Raynaud's phenomenon or scleroderma-like oedemas (hands) indicate an overlap syndrome. This symptomatology is rarely associated with a malignant tumor.

Fatty tissue: Rare but clinically established manifestation of dermatomyositis with indurated painful nodules or plaques on the abdomen, buttocks and arms. Ulcerations and lipodystrophy may occur.

Mucous membranes: in 10% to 20% ulcers of the oral mucosa

Internal organs: involvement of heart, intestine and kidneys. Dysphagia due to weakness of the oropharyngeal muscles. Associated: bronchopneumonia (aspiration by dysphagia), hepato-splenomegaly, nephritis, pressure pain in large nervous systems, psychic changes, focal retinitis peripapillosa, cotton-wool exudate, small streaky hemorrhages in the nerve fiber layer, papilloedema, more rarely episcleritis and scleritis.

Laboratory
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  • Serum: CK i.S. (especially MM-type) up to 50-fold increased, aldolase, GOT, GPT, LDH increased. Creatinine excretion increased in 24h urine.
  • Antibodies have an increasingly important role. A distinction is made between myositis associated antibodies (MAA) and myositis specific antibodies (MSA). Antinuclear antibodies (ANA) can be detected in about 33% of cases. An important indicator for dermatomyositis are antibodies against MI-2. Furthermore, the following antibody profile is possible:
Autoantibodies Frequency (%) Clinical association

Myositis-specific autoantibodies (varies n.Volc burst) DM = Dermatomyositis

Mi-2

20-30%

5%

Classic DM

Paraneoplastic DM

MDAS (CADM140) 50% Amyopathic DM
SAE 5-8% Adults DM
TIF1 (p155/140)

40-75%

20-25%

30%

Paraneoplastic DM

Adults DM

Juvenile DM

NXP-2 25% juvenile dermatomyositis
t-RNA synthetases (e.g. Jo-1) 5-20% Antisynthetase Syndrome
SRP 5% adult dermatomyositis

Myositis-associated antibodies (varies by Volc-Platzer)

Autoantibodies Frequency% Clinical association
Ro (SSA) 19% Antisynthetase Syndrome (Anti-Jo-1 Syndrome
U1-RNP 8% Mixed Connective Tissue Syndrome
PM/Scl (75-100kd) 2% Sclerodermatomyositis
Ku 1% Overlap myositis

  • Blood count: Lymphopenia, often pronounced eosinophilia, also leukocytosis with left shifting occurs.
  • BSG: moderate to medium acceleration.
  • Serum electrophoresis: increase of alpha 2- and gamma-globulin.
  • Urine: creatine and creatininuria. Proteinuria in relapse, myoglobinuria.

Histology
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  • Integument: Uncharacteristic interface dermatitis of varying severity, possibly with mild acanthosis or atrophy with degeneration of the basal keratinocytes.
  • Electron microscopy: Tubulovesicular inclusions in the vascular endothelium.
  • Muscle: segmental muscle fibre necrosis, loss of transverse striation, eosinophilic granular necrosis, interstitial mononuclear infiltrate, possibly vascular alterations with intimal hypertrophy and fibrin deposits in the small arterioles. Relative reduction of CD4 T cells and lymphocytes.
  • Adipose tissue: Mixed septal/lobal panniculitis with dominating infiltrate of lymphocytes, plasma cells and focal membranocystic fat tissue necrosis. Lymphocytic vasculitis may occur.

Diagnosis
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  • Clinic
  • Histology and immunohistology from skin biopsy and muscle biopsy
  • Electromyogram: Short polyphase potentials, fibrillations
  • Creatine excretion in 24-hour urine
  • ANA in majority of patients low-titer positive
  • Myositis-associated AK are (in contrast to polymyositis) rather rare in dermatomyositis (Jo-1-AK, Mi-2-AK). In patients with AK against aminoacyl-t-RNA synthases, SRP or Mi-2, myositis is at the forefront of the disease. Jo-1-AK is of the greatest clinical importance (see below antisynthetase syndrome).
  • For the diagnosis "polymyositis" at least 3 of the following criteria should be positive:
    • Muscle enzymes (creatine kinase)
    • EMG
    • Muscle biopsy.
  • In many cases, the suspected diagnosis must be made solely on the basis of the clinical symptoms, as other parameters are inconsistent.

Differential diagnosis
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  • Systemic lupus erythematosus (mostly acute onset, absence of the Gottron sign; classical serology)
  • Acute contact allergic eczema of the face (flat "contact-related" eczema, possibly weeping (dermatoymositis never weeping), severe itching, no general complaints!)
  • Mixed connective tissue disease (serological clarification)
  • Rosacea erythematosa (At first glance, skin changes are quite similar. Accompanying follicular papules or even pustules exclude DM. Mostly nutritive or emotionally triggered flush phenomena. Never general complaints:-)
  • Dermatomyositis-like skin signs in case of infection by B. burgdorferi, in case of T-cell lymphoma, atopic eczema (serological and histological clarification of the underlying disease).
  • Trichinosis and cysticercosis (myalgias, fatigue, urticarial, often esosinophilic exanthema; marked blood eosinophilia. Eosinophilia would be unusual in dermatomyositis)
  • Myositides of other genesis (no dermatological component)
  • Thyrotoxic myopathy and muscular dystrophies (neurological clarification; the pioneering dermatological phenomena of dermatomyositis are missing).

General therapy
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  • tumour exclusion (especially ovary, lung, pancreas, colon, non-Hodgkin lymphoma) at least 1 time per year
  • Exclusion of bacterial foci, if necessary remediation.
  • In acute phases of illness, bed rest and general robotic measures.
  • Due to the long-term glucocorticoid treatment, recommendations such as a low-salt diet and fluid restriction and, if necessary, the substitution of calcium and vitamin D (Vigantoletten 1000 1Tbl./day) should be carried out in the case of beginning osteoporosis.
  • Physiotherapeutic exercises or physical measures to improve muscle function are also recommended.
  • Photoprotective measures are necessary for all variants of dermatomyositis.

External therapy
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Application of textile and chemical/physical light protection. In individual cases, a short-term, concomitant, low-dose therapy with topical glucocorticoids can be performed.

Internal therapy
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  • Glucocorticoids such as prednisolone (e.g. Decortin H) at a dosage of (at least) 1.0-2.0 mg/kg bw/day In the case of highly acute courses of disease, steroid pulse therapy at a dosage of 1 g/day for 3-5 days can be carried out initially. Continuation with prednisolone at a dosage of 1.0-2.0 mg/kg bw/day, depending on clinical symptoms. Fluorinated glucocorticoids (e.g. dexamethasone, triamcinolone) should be avoided due to their potential to cause myopathy.
  • To save glucocorticoids, combination therapy with azathioprine (Imurek) 1.0-3.0 mg/kg bw/day is recommended at an early stage. Slow dose reduction of the glucocorticoids (e.g. every 2-4 weeks by 5-10 mg/day) depending on the clinical findings down to a maintenance dose (10-15 mg/day), which usually has to be maintained for months to years. Under certain circumstances, the dose may have to be increased again if the clinical findings deteriorate. In addition to the clinical findings, follow-up examinations and activity determinations are carried out by determining the muscle enzymes (creatine kinase, aldolase, lactate dehydrogenase). An outlet test can only be attempted after several months of freedom from symptoms (normalisation of serum creatine kinase values). A prior determination of the thiopurine methyltransferase (TPMT) can be performed to assess genetic mis-metabolism. Contraindications: combination with Allopuriol!
  • Methotrexate (MTX) is an alternative to azathioprine. Start with 7.5-10.0 mg/week p.o. or i.v., increase in weekly steps of 2.5 mg up to a maintenance dose of 25 mg/week Cave! No i.m. injections, as the increase in muscle enzymes means that it is no longer possible to monitor the progress of the treatment!
  • Alternatively: cyclophosphamide (e.g. endoxane) 100-150 mg/day; also described as shock therapy at a dosage of 0.5-1.0 g/m2 KO/month i.v.
  • Alternatively (only case reports): Ciclosporin A (sandimmune) 3.0-5.0 mg/kg bw/day divided into two doses.
  • Alternatively (case reports only): Mycophenolate mofetil (CellCept) 2.0 g/day p.o. Similar effect as azathioprine (antipurine metabolite) with a start-up period of approx. 3 months.
  • Alternative: high-dose immunoglobulins (IVIG) in doses of 0.5-1.0 g/kg bw/day for 3 days i.v. (repeated every 4 weeks) especially in therapy-resistant active dermatomyositis patients. Intravenous immunoglobulin therapy ( IVIG therapy) has also proven to be effective in juvenile forms of dermatomyositis. Cave! Very high therapy costs!
  • Alternative: in case of insufficient response to glucocorticoids and IVIG, initiation of a therapy with Rituximab (Mabthera) 100-375 mg/m2 KO i.v. 4 times a week. Clear evidence for the success of this therapy is missing so far.
  • Alternative: In severe, therapy-resistant cases, plasmapheresis remains as the ultima ratio; confirmed results are still pending.
  • In current clinical studies: Eculizumab (anti-complement C5), tocilizumab (anti-interleukin-6), anakinra (anti-IL-1-receptor, see interleukin-1), gevokizumab (anti-interleukin-1beta), anti-interleukin-17 (see interleukin-17).

Progression/forecast
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Unpredictable development of the course. The duration of the disease varies (months to decades). In smaller cohorts the 5-year survival rate was 95% and the 10-year survival rate 84%. 50-75% of the patients treated with immunosuppressive drugs show a significant improvement of the clinical findings. Higher age and association with a malignoma are associated with a poor prognosis.

Note(s)
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In individual cases the dermatological phenomena of "dermatomyositis" are also observed without myositis, thus as minus varinates: "dermatomyositis sine myositis".

Literature
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  1. Bernard P, Bonnetblanc JM (1993) Dermatomyositis and malignancy. J Invest Dermatol 100:128-132
  2. Bruce H et al (2009) Cutaneous manifestations of internal malignancy. Cancer J Clin 59:73-98
  3. Callen JP, Wortmann RL (2006) Dermatomyositis. Clin Dermatol 24: 363-373
  4. Cherin P et al (1991) Efficacy of intravenous gammaglobulin therapy in chronic refractory polymyositis and dermatomyositis: an open study with 20 adult patients On J Med 91: 162-168
  5. Dalakas MC (2003) Therapeutic approaches in patients with inflammatory myopathies. Seminar Neurol 23: 199-206
  6. Dalakas MC (2003) Polymyositis and dermatomyositis. Lancet 57: 971-982
  7. Gardner-Medwin JM et al (2002) Incidence of Henoch-Schonlein purpura, Kawasaki disease, and rare vasculitides in children of different ethnic origins. Lancet 360: 1197-1202
  8. Gürcan HM et al (2009) A review of the current use of rituximab in autoimmune diseases. Int Immunopharmacol 9: 10-25
  9. Levine TD (2005) Rituximab in the treatment of dermatomyositis: an open-label pilot study. Arthritis Rheum 52: 601-607
  10. Mendez EP (2003) US incidence of juvenile dermatomyositis, 1995-1998: results from the National Institute of Arthritis and Musculoskeletal and Skin Diseases Registry. Arthritis Rheum 49: 300-305
  11. Moghadam-Kia S et al (2017) Modern Therapies for Idiopathic Inflammatory Myopathies (IIMs): Role of Biologics. Clin Rev Allergy Immunol 52:81-87.

  12. Mori H et al (2005) Relapse of dermatomyositis after 10 years in remission following curative surgical treatment of lung cancer. J Dermatol 32: 290-294

  13. Sato S et al (2005) Autoantibodies to a 140-kd polypeptide, CADM-140, in Japanese patients with clinically amyopathic dermatomyositis. Arthritis Rheum 52: 1571-1576
  14. Sunderkötter C et al (2016) Leitlinie Dermatomyositis - Extract from the interdisciplinary S2k guideline on myositis syndromes of the German Society of Neurology. JDDG 14: 321-333
  15. Tersiguel AC et al (2014) Prevalence of cancer in the Afro-Caribbean population presenting dermatomyositis and anti-synthetase syndrome: a preliminary study conducted at Pointe-à-Pitre University Hospital, 2000-2012 Ann Dermatol Venereol141:575-580

  16. Unverricht H (1887) On a peculiar form of acute muscle inflammation with a clinical picture similar to trichinosis. Münch med Wschr 34: 488-492
  17. Wagner EL (1863) Case of a rare muscle disease. Arch healing 4: 282-283

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Last updated on: 29.10.2020