Juvenile Dermatomyositis

NeuroLearn NeuroHelp Muscle @

Background    Histopathology & Immunohistochemistry    Dermatomyositis vs. polymyositis

BACKGROUND AND CLINICAL INFORMATION: Head  

Summary: Dermatomyositis has different clinical features in adult and childhood cases but similar pathology. Dermatomyositis in childhood is an inflammatory muscle disease that is not linked with malignancy. They may overlap with other connective tissue disease and the degree of skin involvement is variable. The consistent abnormalities in blood vessels highly suggest that dermatomyositis is closely related to connective diseases. The three cardinal clinical features are muscle weakness, skin lesions and constitutional symptoms such as malaise, listlessness and lethargy. Low-grade fever is common. The salient pathologic features are inflammatory cell infiltration, peripheral atrophy, and vasculopathy. Ultrastructurally there are tubuloreticular structures and cylindrical confronting cisternae.

Peak age: Around 9 years old.

Sex: male to female ratio is 2:3.

Autoantibodies: About 10% of juvenile cases have anti-MI-2 antibodies (antinuclear antibody), other myositis specific antibodies may also be present.

Clinical features:

·        The three cardinal features are muscle weakness, skin lesions and constitutional symptoms such as fever and malaise. Onset of symptoms is classically insidious and the rash and weakness appear together. The childhood cases tend to have more wide spread organ involvement than adult cases.

·        Weakness and pain: usually proximal, symmetrical, and tends to starts in lower extremities. The arms and neck can alos be involved. Younger patients may have more generalized weakness. Pain and tenderness may occur but not constant; palpable nodules may be present. Contracture is often found.

·        Constitutional symptoms: low-grade fevere is often present accompanied by lethargy and listlessness.

·        Skin lesions are highly variable. They are more often subtle than florid. The most common presentation is violaceous discoloration of the upper eyelids and a malar (butterfly) erythematous eruption that is slightly scaly.

·        Mass: Occasionally, dermatomyositis may present as small masses.

·        Calcinosis: This is much more common in juvenile than adult cases, usually in the intertistitial tissue of the muscle or subcutaneous tissue. Calcification is most often found two years after the onset of disease and is a good indicator of chronicity. Calcifications may subsequently resovle.

·        Other organs: Colonic perforation due to vascular occlusion has been well documented. Arthritis, lymphadenopathy and splenomegaly, respiratory system, gastrointestinal tract, cardiovascular and renal functions may all be altered.

·        Differences from adult cases: Dermatomyositis has a distinctive clinical presentation in children and is relatively common. In contrast to adult cases, they are not linked with malignancy. They have a different pattern of autoantibodies and they tend to have widespread involvement of organs.

·        Polymyositis is quite rare and can represent dermatomyositis without skin involvement. In these cases, however, acute and chronic myositis of other etiology such as virus must be carefully ruled out.

Pathogenesis: Damage to the muscle fibers is largely resulted from vascular damage including damage of endothelial cells, thrombosis and destruction of capillaries.

HISTOPATHOLOGY AND IMMUNOHISTOCHEMISTRY: Head  

• Light microscopy and histochemistry:

• Variability: The pathology varies from case to case and from muscle to muscle.

• Inflammatory infiltrates: Most but not all cases have inflammatory cell infiltration consistuted by lymphocytes, macrophages, and plasma cells. They are usually in septa or less commonly inside fascicles or both. Both B- and T-cells are present and T-cells are more common around blood vessels. Unlike polymyositis, partial invasion of non-necrotic muscle fibers is not seen.

• Vessels: Thrombosed and recanalized vessels can be found. There is a progressive destruction of capillaries that may vary from region to region and the residual capillaries may be dilated. Blood vessels may also look abnormal and semithin sections are helpful.

• Peripheral atrophy: In childhood cases, atrophy of muscle cells on the periphery of fascicle is the most helpful diagnostic sign.

• Necrotic: Necrotic fibers are seen in most adult cases but not all childhood cases. Bundles of necrotic fibers that suggest infarction may be seen. Macrophages may not be abundant and the necrotic foci are surrounded by plump myoblasts or myotubules.

• Regenerating fibers: They are found in the same distribution as necrotic fibers. They may appear as groups of small fibers and may suggest neurogenic atrophy.

• Punched out fibers: Junvenile cases tend to have punched-out areas (vacuoles) of myofibrillar loss within fibers.

• Z-disc streaming may be present (demonstrated by modified Gomori’s trichrome or in semithin sections).

• Myofibrillary loss: This is more prominent in juvenile cases and less frequent and less pronounced in adult cases.

Immunohistochemistry:

• Class I MHC antigens are expressed by damaged fibers but not usually in intact fibers (unlike polymyositis).

• Membrane attack complex in capillary walls can be demonstratrated by immunohistochemistry in both muscle and skin lesions. Acid phosphatase is demonstrated in blood vessels indicating phagocytosis of capillary debris.

Electron microscopy:

   Endothelial changes:

• Abnormal endothelial cells are present in all cases of dermatomyositis and the changes are similar in adult and juvenile cases. Blood vessel changes in the muscle may be different from vessels from other regions. Vessels in blood vessels are often necrotic. Blood vessels often contains enlarged endothelial cells that contains an increased number of organelles, autophagic vacuoles, lipid droplets, multivesicular bodies, and an excess amount of intermediate filaments. Empty capillary tubes are almost always seen.

• Tubuloreticular structures in endothelial cells: They may contain tubuloreticular structures (underlating tubules) in the smooth endoplasmic reticulum, most often seen in the perinuclear cisternae. They may also be seen in lymphocytes and even in vessels of the skin but never in muscle cells. They are highly suggestive but not diagnostic for dermatomyositis and they may be seen in other conditions and viral infection.

• Cylindrical confronting cisternae: They are also highly suggestive of dermatomyositis but can also be seen in othe conditions including viral infection. These structures are not as common as tubuloreticular structures.

   Mucle cells:

• Z-disc streaming and areas with complete lost of myofibrils. A variety of non-specific pathology secondary to ischemia are present.