INFLAMMATORY MYOPATHIES

INFLAMMATORY MYOPATHIES is a topic covered in the Harrison's Manual of Medicine.

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The most common group of acquired and potentially treatable skeletal muscle disorders. Five major forms: dermatomyositis (DM), inclusion body myositis (IBM), polymyositis (PM), immune-mediated necrotizing myopathy, and antisynthetase syndrome. Usually present as progressive and symmetric muscle weakness; extraocular muscles spared but pharyngeal weakness (dysphagia) and head drop from neck muscle weakness are common. Respiratory muscles may be affected in advanced cases. IBM is characterized by early involvement of quadriceps (leading to falls) and distal muscles; IBM may have an asymmetric pattern. Progression is over weeks or months in PM and DM, but typically over years in IBM. Skin involvement in DM may consist of a heliotrope rash (blue-purple discoloration) on the upper eyelids with edema, a flat red rash on the face and upper trunk, or erythema over knuckles (Gottron’s sign). A variety of cancers are associated with DM. Features of each disorder are summarized in Table 198-1.

TABLE 198-1: Inflammatory Myopathies: Clinical and Laboratory Features
DISORDERSEXAGE OF ONSETRASHPATTERN OF WEAKNESSLABORATORY FEATURESMUSCLE BIOPSYCELLULAR INFILTRATERESPONSE TO IS THERAPYCOMMON ASSOCIATED CONDITIONS
DMF > MChildhood and adultYesProximal > distalNormal or increased CK (up to 50× normal or higher); various MSAs (anti-MDA5, anti-TIF1, anti-Mi-2, anti-NXP2)Perimysial and perivascular inflammation; IFN-1 regulated proteins (MHC-1, MxA), MAC deposition on capillariesCD4+ Dendritic cells; B cells; macrophagesYesMyocarditis, ILD, malignancy, vasculitis, other CTDs
PMF > MAdultNoProximal > distalIncreased CK (up to 50× normal or higher)Endomysial and perivascular inflammation; ubiquitous expression of MHC-1CD8+ T-cells; macrophages; plasma cellsYesMyocarditis, ILD, other CTDs
NMM = FChildren and adultsNoProximal > distalElevated CK (> 10× normal or higher); anti-HMGCR or anti-SRP antibodiesNecrotic muscle fibers; minimal inflammatory infiltrateMacrophages in necrotic fibers undergoing phagocytosisYesMalignancy, CTD, HMGCR antibody cases can be triggered by statin use
ASSF > MChildren and adultsSometimesProximal > distalElevated CK (>10× normal or higher); antisynthetase antibodiesPerimysial and perivascular inflammation; perimysial fragmentation with alkaline phosphatase staining; perimysial muscle damage with necrosisCD4+ Dendritic cells; B cells; macrophagesYesNon-erosive arthritis, ILD, Raynaud phenomenon, mechanic hands, and fever
IBMM > F

Older adults

(>50 yrs)

NoProximal and distal; predilection for: finger/wrist flexors, knee extensorsNormal or mildly increased CK (usually <10× normal); anti-cN-1A antibodies; large granular lymphocytes on flow cytometry and reduced CD4/CD8 ratio with increased CD8 countEndomysial and perivascular inflammation; ubiquitous expression of MHC-1; rimmed vacuoles; p62, LC3, TDP-43 aggregates; EM: 15–18 nm tubulofilaments; ragged red and COX negative fibersCD8+ T-cells; macrophages; plasma cells; myeloid dendritic cells; large granular lymphocytesNone or minimalGranular lymphocytic leukemia/lymphocytosis, sarcoidosis, SICCA or Sjogren’s syndrome
Abbreviations: CK, creatine kinase; cN-1A, cytosolic 5′-nucleotidase 1A; CTDs, connective tissue diseases; COX, cytochrome oxidase; DM, dermatomyositis; F, female; g, immunoglobulin; IBM, inclusion body myositis; IFN-1, type 1 interferon; ILD, interstitial lung disease; IS, immunosuppressive; M, male; MAC, membrane attack complex; MDA5, melanoma differentiation antigen; MHC-1, major histocompatibility antigen 1; NCP2, nuclear matrix protein 2 (NXP2); NM, necrotizing myopathy; PM, polymyositis; TIF1, transcriptional intermediary factor 1.
Source: Adapted with permission from Amato AA, Russell JA (eds): Neuromuscular Disorders, 2nd ed. New York, McGraw-Hill; 2016.

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The most common group of acquired and potentially treatable skeletal muscle disorders. Five major forms: dermatomyositis (DM), inclusion body myositis (IBM), polymyositis (PM), immune-mediated necrotizing myopathy, and antisynthetase syndrome. Usually present as progressive and symmetric muscle weakness; extraocular muscles spared but pharyngeal weakness (dysphagia) and head drop from neck muscle weakness are common. Respiratory muscles may be affected in advanced cases. IBM is characterized by early involvement of quadriceps (leading to falls) and distal muscles; IBM may have an asymmetric pattern. Progression is over weeks or months in PM and DM, but typically over years in IBM. Skin involvement in DM may consist of a heliotrope rash (blue-purple discoloration) on the upper eyelids with edema, a flat red rash on the face and upper trunk, or erythema over knuckles (Gottron’s sign). A variety of cancers are associated with DM. Features of each disorder are summarized in Table 198-1.

TABLE 198-1: Inflammatory Myopathies: Clinical and Laboratory Features
DISORDERSEXAGE OF ONSETRASHPATTERN OF WEAKNESSLABORATORY FEATURESMUSCLE BIOPSYCELLULAR INFILTRATERESPONSE TO IS THERAPYCOMMON ASSOCIATED CONDITIONS
DMF > MChildhood and adultYesProximal > distalNormal or increased CK (up to 50× normal or higher); various MSAs (anti-MDA5, anti-TIF1, anti-Mi-2, anti-NXP2)Perimysial and perivascular inflammation; IFN-1 regulated proteins (MHC-1, MxA), MAC deposition on capillariesCD4+ Dendritic cells; B cells; macrophagesYesMyocarditis, ILD, malignancy, vasculitis, other CTDs
PMF > MAdultNoProximal > distalIncreased CK (up to 50× normal or higher)Endomysial and perivascular inflammation; ubiquitous expression of MHC-1CD8+ T-cells; macrophages; plasma cellsYesMyocarditis, ILD, other CTDs
NMM = FChildren and adultsNoProximal > distalElevated CK (> 10× normal or higher); anti-HMGCR or anti-SRP antibodiesNecrotic muscle fibers; minimal inflammatory infiltrateMacrophages in necrotic fibers undergoing phagocytosisYesMalignancy, CTD, HMGCR antibody cases can be triggered by statin use
ASSF > MChildren and adultsSometimesProximal > distalElevated CK (>10× normal or higher); antisynthetase antibodiesPerimysial and perivascular inflammation; perimysial fragmentation with alkaline phosphatase staining; perimysial muscle damage with necrosisCD4+ Dendritic cells; B cells; macrophagesYesNon-erosive arthritis, ILD, Raynaud phenomenon, mechanic hands, and fever
IBMM > F

Older adults

(>50 yrs)

NoProximal and distal; predilection for: finger/wrist flexors, knee extensorsNormal or mildly increased CK (usually <10× normal); anti-cN-1A antibodies; large granular lymphocytes on flow cytometry and reduced CD4/CD8 ratio with increased CD8 countEndomysial and perivascular inflammation; ubiquitous expression of MHC-1; rimmed vacuoles; p62, LC3, TDP-43 aggregates; EM: 15–18 nm tubulofilaments; ragged red and COX negative fibersCD8+ T-cells; macrophages; plasma cells; myeloid dendritic cells; large granular lymphocytesNone or minimalGranular lymphocytic leukemia/lymphocytosis, sarcoidosis, SICCA or Sjogren’s syndrome
Abbreviations: CK, creatine kinase; cN-1A, cytosolic 5′-nucleotidase 1A; CTDs, connective tissue diseases; COX, cytochrome oxidase; DM, dermatomyositis; F, female; g, immunoglobulin; IBM, inclusion body myositis; IFN-1, type 1 interferon; ILD, interstitial lung disease; IS, immunosuppressive; M, male; MAC, membrane attack complex; MDA5, melanoma differentiation antigen; MHC-1, major histocompatibility antigen 1; NCP2, nuclear matrix protein 2 (NXP2); NM, necrotizing myopathy; PM, polymyositis; TIF1, transcriptional intermediary factor 1.
Source: Adapted with permission from Amato AA, Russell JA (eds): Neuromuscular Disorders, 2nd ed. New York, McGraw-Hill; 2016.

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