Juvenile Dermatomyositis, Inflammation, and Calcifications

Juvenile Dermatomyositis, Inflammation, and Calcifications

Autoimmune diseases, when the immune system attacks certain areas of the body, affect more than 23 million Americans, more so women than men. Some autoimmune diseases are well known, such as systemic lupus erythematosus, and others are rarer, such as juvenile dermatomyositis. Juvenile dermatomyositis (JDM) is found in people less than 18 years of age and is the most common pediatric inflammatory myopathy in children (Urganus et al., 2009). There are up to five cases per million children in the U.S. (Ravelli et al., 2009). Ideas as to why this disease occurs have been proposed with no definite answers. The symptoms are quite broad and make it difficult to reach a diagnosis. Over the years, advances in treatment have helped put the disease in remission for some individuals, but for others, without treatment, the disease can result in chronic disability or even death.

JDM causes inflammation of the connective tissues in the body such as tendons, blood, and adipose tissue, which in turn cause muscle weakness and a skin rash. The characteristic rash of JDM developed on the eyelids, cheeks, elbows, and knees is called a heliotrope rash, and Gottron’s papules is a rash which develops on the fingers and nail folds. Symptoms of the disease include weakness of the upper and lower extremities, causing an overall weakness of the body, fever, muscle pain, arthritis, fatigue, and weight loss. Dysphagia (difficulty swallowing) and lipodystrophy (abnormal distribution of fat) are both very common symptoms in JDM. Weakness of the legs and arms can hinder physical movement such as walking and sitting up on one’s own, showering, and sometimes just the simple act of sitting. A muscle biopsy, which can show the amount of damage to the muscle, is usually done to make the correct diagnosis.

The development of calcifications is common in children with juvenile dermatomyositis. Up to 30% of children with JDM are affected by the complication of pathologic soft tissue calcifications (Urganus et al., 2009). Calcium deposits are believed to affect high areas of inflammation of the body, mainly the muscular extremities and joints.  Inflammation is the result of a type of immune response where the body rushes certain white blood cells to the infected area, causing redness and pain. In juvenile dermatomyositis, however, the body signals for calcifications to form at those infected areas. These localized regions of pain and swelling make it hard for the joints and muscles to be used. These symptoms can mimic a serious infection, making it difficult to diagnose (Kumar and Aggarwal, 2010). The inflammation is said to be the bodies’ way of “healing” itself and in turn, calcium deposits are formed at these areas as a way of masking the so-called injury. These calcifications, similar to calcified areas of heart valves, increase the prevalence of morbidity and mortality. “A delay in diagnosis is associated with the presence of calcifications, indicating that chronic inflammation and/or tissue injury plays a role.” (Pachman et al., 2006).

The composition of calcifications is very similar to bone.  Both contain the bone matrix proteins osteopontin, osteonectin, and bone sialoprotein, although calcifications contain more osteonectin and less osteopontin than regular bone (Pachman et al., 2006). The bone-like structure of calcifications is the main reason they are so debilitating. Growth of unwanted, hard, brick-like structures inhibits movement and causes severe pain throughout the body.

Environmental as well as genetic factors may play a role in the prevalence of JDM. Like some recessive genes that are inherited but are not part of an individuals’ phenotype, JDM might be caused by a recessive allele that gets triggered by certain things in the environment, such as sun (ultraviolet radiation) exposure. “Current evidence suggests that autoimmune diseases result from environmental exposures, such as UV radiation, in genetically susceptible individuals … and is associated with diseases that have a photosensitive rash such as juvenile dermatomyositis” (Love et al., 2009). One of the first symptoms to be recognized in patients with JDM is this particular rash that seems to get worse when out in the sun and seems to persist even with relative amounts of sunscreen. The more exposure to UV radiation, the more occurrences of inflammation, and with increased amounts of inflammation, calcifications are formed.

Genetic components are being studied in the prevalence of JDM. A certain recessive allele, TNF alpha-308A, has been found in children with JDM who did not receive treatment right away, resulting in calcifications. The increased frequency of the TNF alpha-308A allele may be the cause of the inflammation occurring in patients with JDM (Pachman et al., 2000). The autoantigen Mi-2 is an antigen that triggers an immune response towards ones own body, creating autoantibodies. Autoantibodies are helpful in creating a diagnosis for a person with juvenile dermatomyositis because there will be high amounts of these found in the muscle (Casciola-Rosen et al., 2005).

Treatment for juvenile dermatomyositis and calcifications varies, but is quite similar to treatment for most autoimmune diseases. The most common medicinal treatment would be the use of oral corticosteroids i.e. prednisone. Corticosteroids are an immunosuppressant that weaken the body’s immune system and generally slow down the progress of the disease. Slowing down the progress makes for less inflammation which will not trigger the body to produce calcifications. For more severe cases of JDM, the use of intravenous steroids such as methylprednisolone would be used. Methotrexate, a chemotherapeutic medication, has been used to treat JDM, as well as Plaquenil, another medication to reduce the amount of inflammation in the body. Colchicine, a medicine used to treat gout, has been used in treating calcifications along with the medication Probenecid. Physical and occupational therapy can be paired with medicinal treatment to help with the limited range of motion caused by the calcifications. When treatment fails, surgical removal of the calcifications would be the last option, but even that shows little success for the fact that the calcifications usually grow back.

Medicine has come a long way in discovering new ways to treat juvenile dermatomyositis. Symptoms of JDM are very extensive and can lead to misdiagnosis and incorrect treatments. In the past, people diagnosed with JDM had little chance of survival because of the lack of knowledge about the disease. Now, there are several treatments that can work to stabilize the disease such as medicinal (corticosteroids, chemotherapeutic drugs), physical therapy, and surgical treatments. Calcifications can be the main dilemma in patients with JDM, and often are linked to a late diagnosis with possible chronic handicaps, but even then, a positive outcome can be reached. Prognosis is promising and when caught early, with the correct treatments, chances of remission are great.

http://onlinelibrary.wiley.com/doi/10.1002/1529-0131(200010)43:10%3C2368::AID-ANR26%3E3.0.CO;2-8/abstract  (pachman 2000)

http://onlinelibrary.wiley.com/doi/10.1002/art.22158/full   (pachman 2006)

http://onlinelibrary.wiley.com/doi/10.1002/art.24702/full   (Love)

http://onlinelibrary.wiley.com/doi/10.1002/art.24391/full  (urganus)

http://resources.metapress.com/pdf-preview.axd?code=d8711149vu43l773&size=largest    (kumar and aggarwal)

http://onlinelibrary.wiley.com/doi/10.1002/acr.20015/full  (Ravelli)

http://jem.rupress.org/content/201/4/591.full (casciola-Rosen)

Abstract:
Juvenile Dermatomyositis (JDM) is an autoimmune disorder affecting children. Its main cause is unknown but symptoms can be devastating. Inflammation is said to be the primary culprit in this disease. The inflammation can cause calcifications to form in the upper and lower extremities of the body. UV radiation and children who are genetically susceptible can promote the disease. Treatments have advanced within the past 20 years, making prognosis better and remission possible.

Casciola-Rosen, L., Nagaraju, K., Plotz, P., Wang, K., Levine, S., Gabrielson, E., Corse, A., Rosen, A. (2005), Enhanced autoantigen expression in regenerating muscle cells in idiopathic inflammatory myopathy. The Journal of Experimental Medicine, 201: 591-601.

Kumar, T. S., Aggarwal, A. (2010), Approach to a patient with connective tissue disease. Symposium on Pediatric Rheumatology-II.
Love, L. A., Weinberg, C. R., McConnaughey, D. R., Oddis, C. V., Medsger, T. A., Reveille, J. D., Arnett, F. C., Targoff, I. N. and Miller, F. W. (2009), Ultraviolet radiation intensity predicts the relative distribution of dermatomyositis and anti–Mi-2 autoantibodies in women. Arthritis & Rheumatism, 60: 2499–2504.

Pachman, L. M., Liotta-Davis, M. R., Hong, D. K., Kinsella, T. R., Mendez, E. P., Kinder, J. M. and Chen, E. H. (2000), TNFα-308A allele in juvenile dermatomyositis: Association with increased production of tumor necrosis factor α, disease duration, and pathologic calcifications. Arthritis & Rheumatism, 43: 2368–2377.

Pachman, L. M., Veis, A., Stock, S., Abbott, K., Vicari, F., Patel, P., Giczewski, D., Webb, C., Spevak, L. and Boskey, A. L. (2006), Composition of calcifications in children with juvenile dermatomyositis: Association with chronic cutaneous inflammation. Arthritis & Rheumatism, 54: 3345–3350.

Ravelli, A., Trail, L., Ferrari, C., Ruperto, N., Pistorio, A., Pilkington, C., Maillard, S., Oliveira, S. K., Sztajnbok, F., Cuttica, R., Beltramelli, M., Corona, F., Katsicas, M. M., Russo, R., Ferriani, V., Burgos-Vargas, R., Magni-Manzoni, S., Solis-Valleoj, E., Bandeira, M., Zulian, F., Baca, V., Cortis, E., Falcini, F., Alessio, M., Alpigiani, M. G., Gerloni, V., Saad-Magalhaes, C., Podda, R., Silva, C. A., Lepore, L., Felici, E., Rossi, F., Sala, E. and Martini, A. (2010), Long-term outcome and prognostic factors of juvenile dermatomyositis: A multinational, multicenter study of 490 patients. Arthritis Care & Research, 62: 63–7.

Urganus, A. L., Zhao, Y.-d. and Pachman, L. M. (2009), Juvenile dermatomyositis calcifications selectively displayed markers of bone formation. Arthritis Care & Research, 61: 501–508.

Tags: calcifications inflammation