What Are the Complications of Duchenne Muscular Dystrophy?

Patient Presentation
A 17-year-old male with Duchenne muscular dystrophy (DMD) came to the intensive care unit intubated after nephrolithotripsy and surgical evacuation of ureteral stones bilaterally.
The patient had increasing renal colic and with conservative management did not improve.
The past medical history showed that he was diagnosed as a preschooler when he was noted to have muscle weakness.
He became non-ambulatory at age 11. He currently uses a mechanized wheelchair. He had a history of a single urinary stone that was treated conservatively 1 year previously.
The family history was negative for neuromuscular or genetic disease.
The pertinent physical exam showed an intubated male who was awakening after anesthesia.
His face was symmetric with brisk pupillary reflexes.
Heart examination revealed a regular rate and rhythm without murmurs.
He had significant weakness of all extremities (2/5).
He had contractures of elbows, wrists, knees and ankles and moderate right thoracolumbar scoliosis.
A foley catheter was in place with light pink urine.
The diagnosis of ureteral stone extraction and DMD were made.
The patient’s clinical course improved over next day allowing him to be extubated and later transferred to the regular inpatient floor.
He remained on his home respiratory regiment of BiPAP (bilateral positive airway pressure) at night.
He went home on day 3 post-operatively and was to followup with urology in one week.
The laboratory evaluation of the renal caliculi showed them to be calcium oxalate.

Discussion
Duchenne muscular dystrophy is a progressive, muscle-wasting, lethal disease that affects about 1 in 3500 boys.
It is an X-linked recessive disorder with ~1/3 of patients having a spontaneous mutation.
The genetic abnormality causes an absence or marked deficiency in the quantity of dystrophin protein in muscles.
Muscle cells without dystrophin are more easily damaged during contraction with muscle inflammation, necrosis and fibrosis occurring.
Patients classically have proximal muscle weakness (neck flexor, anterior abdominal, hip and shoulder girdle muscles) that presents usually by late preschool/early school-age. This is associated with a greatly elevated muscle creatinine phosphokinase level.
Over ime, patients become weaker and lose the ability to ambulate between 7-12 years of age typically. Early death in the teens and early 20s is usually due to complications of respiratory insufficiency secondary to muscle weakness.

Prednisone and Deflazacort (a corticosteroid similar to prednisone) have been shown to improve muscle strength and function and are recommended for treatment. Their mechanism of action is as an immunosuppressant.
Prednison or Deflazacort are recommended to start before symptoms and usually are begun in the preschool period. They are stopped based upon patient respone and side effect profile.
Other treatments being evaluated include methods to increase protein synthesis, decrease proteolysis, decrease the inflammatory response, and methods to increase muscle proliferation and regeneration.
Ultimately, gene therapy may be the answer to long-term cure.

Learning Point
Common complications in patients with DMD include:

  • Cardiac
    • Arrhythmias
    • Cardiomyopathy
  • Orthopaedic problems
    • Joint contractures
    • Osteopenia – because of immobility but also secondary to steroid treatment
    • Scoliosis
  • Infectious
    • Pulmonary infections
  • Pulmonary
    • Respiratory insufficiency with decreased total lung capacity, decreased residual lung volume
  • Steroid treatment problems
    • Behavioral changes
    • Bone demineralization
    • Cushingoid appearance
    • Growth suppression
    • Hirsutism
    • Weight gain
  • Miscellaneous
    • Aspartate aminotransferase (AST) elevation
    • Mental retardation
    • Renal stones secondary to bone demineralization

Questions for Further Discussion
1. What other congenital myopathies are in the differential diagnosis of DMD?
2. What resources are available for families with chronic diseases in my local community?
3. When is mechanical ventilation appropriate for patients with DMD?

Related Cases

To Learn More
To view pediatric review articles on this topic from the past year check PubMed.

Evidence-based medicine information on this topic can be found at the National Guideline Clearinghouse and the Cochrane Database of Systematic Reviews.

Information prescriptions for patients can be found at MedlinePlus for this topic: Muscular Dystrophy

To view current news articles on this topic check Google News.

To view images related to this topic check Google Images.

Roland EH.
Muscular dystrophy.
Pediatr Rev. 2000 Jul;21(7):233-7.

Tidball JG, Wehling-Henricks M.
Evolving therapeutic strategies for Duchenne muscular dystrophy: targeting downstream events.
Pediatr Res. 2004 Dec;56(6):831-41.

Moxley RT 3rd, Ashwal S, Pandya S, Connolly A, Florence J, Mathews K, Baumbach L, McDonald C, Sussman M, Wade C. Quality Standards Subcommittee of the American Academy of Neurology; Practice Committee of the Child Neurology Society.
Practice parameter: corticosteroid treatment of Duchenne dystrophy: report of the Quality Standards Subcommittee of the American Academy of Neurology and the Practice Committee of the Child Neurology Society.
Neurology. 2005 Jan 11;64(1):13-20.

ACGME Competencies Highlighted by Case

  • Patient Care
    1. When interacting with patients and their families, the health care professional communicates effectively and demonstrates caring and respectful behaviors.
    2. Essential and accurate information about the patients’ is gathered.
    4. Patient management plans are developed and carried out.
    7. All medical and invasive procedures considered essential for the area of practice are competently performed.
    8. Health care services aimed at preventing health problems or maintaining health are provided.
    9. Patient-focused care is provided by working with health care professionals, including those from other disciplines.

  • Medical Knowledge
    10. An investigatory and analytic thinking approach to the clinical situation is demonstrated.
    11. Basic and clinically supportive sciences appropriate to their discipline are known and applied.

  • Systems Based Practice
    24. Cost-effective health care and resource allocation that does not compromise quality of care is practiced.
    25. Quality patient care and assisting patients in dealing with system complexities is advocated.

    Author
    Donna M. D’Alessandro, MD
    Professor of Pediatrics, University of Iowa Children’s Hospital

    Date
    October 27, 2008

  • What Are the Most Common Food Allergies?

    Patient Presentation
    A 14-year-old female came to the emergency room because of increasing respiratory distress.
    She was known to be allergic to peanuts and other tree nuts and had moderate, persistent asthma.
    She was visiting relatives and the entire family had gone hiking and picked up butternuts and walnuts.
    She did not pick up or touch any of the nuts, but did ride home in a station wagon where some of the nuts were transported in the back end of the car.
    During the ride, she became nauseated. The family stopped for a while and she seemed to be better. However, when the car ride resumed so did the nausea.
    When they reached home she was wheezing. Her rescue inhaler did not help and her parents took her to the emergency room. She did not use her injectable epinephrine.
    The past medical history showed peanuts and tree nuts triggering significant asthma flares and severe pruritus. She had never had laryngospasm or needed intubation.
    The most recent episode had been 2 years previous when she had ingested some frozen yogurt that initially had a cookie in it.
    She did not eat the cookie, but it was suspected that the cookie’s oil was peanut or tree nut and had permeated the yogurt.
    The family history showed mild asthma and eczema.
    The review of systems was otherwise normal.
    The pertinent physical exam showed a wide-eyed young female who could speak with difficulty but was alert and oriented. Her heart rate was 148 beats/minute, respiratory rate was 64 respirations/minute, her blood pressure was 108/70 and her saturation was 90% on room air.
    Her skin examination revealed diffuse hives. HEENT was normal. She had increased work of breathing with intercostal retractions and tracheal tugging. She had diffuse wheezing throughout her lung examination.
    The diagnosis of a severe allergic reaction was made.
    She and her family realized that either she inadvertently contacted the nuts, or that the oils from the nuts were aerosolized within the car triggering her symptoms.
    In the emergency room, the patient’s clinical course improved somewhat with subcutaneous epinephrine, oral diphenhydramine and oral prednisone.
    She, her parents and the emergency room staff felt she should be monitored and so she was admitted overnight and then discharged home.

    Discussion
    Food allergies are relatively common but it can be difficult to tease out if it is a true allergy, a food intolerance or is actually something else.
    Risk factors that increase the likelihood of food allergy include:

    • Reactions that occur minutes to hours of the ingestion
    • Accidental ingestion of same food that produces the same symptoms
    • Onset of symptoms as an infant or young child
    • Close family history of other allergic diseases such as allergic rhinitis, asthma, atopic dermatitis or food allergies
    • The suspected food is known to be higher risk for producing allergic reactions

    Children with a possible food allergy may receive testing by skin-prick, patch testing or RAST (radioallergosorbent testing).
    RAST is a blood test that has a high sensitivity but has only ~50% specificity. It is commonly performed in young children because it is often easier to obtain blood than to do skin-prick or patch testing. It also does not carry a risk of inducing potential allergic reactions.

    Children with a history of anaphylaxis should be treated as if they have severe food allergies and should be evaluated and treated by a specialist.
    Children with a history of symptoms after ingestion of a food, but no anaphylaxis and with positive testing may need further testing with a blinded or unblinded food challenge.
    Children with a history of symptoms after ingestion of a food, but no anaphylaxis and negative testing often can be allowed the food and monitored. But if there is a family history of anaphylaxis the patient should be evaluated by a specialist and most likely will have the food re-introduced in a supervised setting.

    If in doubt about if the child is allergic, they should be treated as if they are.
    Patients should be given injectable epinephrine and have it available at all times. This may mean that they need several injectors to be available at school, home, other locations the patient frequents and also available in backpacks/purses, etc. if the child is old enough to use the injector themselves.
    Patients and parents need to be told that if the epinephrine is given then they must go to the nearest hospital as soon as possible for evaluation. Second injectors are also sometimes recommended as the epinephrine wears off in about 20 minutes and this may not be enough time for the patient to have gotten to the hospital yet. The second epinephrine injection can therefore be given enroute.

    Parents should be educated to CONSTANTLY read all labels and ask about food preparation at restaurants, schools and other non-home locations.
    Label reading is extremely important as ingredients and preparation may have changed from the last time the food was ingested.
    Generic and brand name products may be prepared differently so every label must be checked.
    Patients and parents should be educated that if they are in doubt about a food, the entire food and anything it came in contact with should be avoided (see the yogurt incident above).

    Peanut allergies are highly genetic with a child have 7 times greater risk of being allergic if his/her parent or sibling has a peanut allergy. In monozygotic twins there is a 64% likelihood of peanut allergy if the other twin has the problem.
    Genetics does not account for all of the reasons for food allergy and it may be multi-factorial. There are several hypotheses for food allergies which include dual-allergens, antioxidants, dietary fat, vitamin D, and general hygiene.

    Learning Point
    The prevalence of food allergies depends on the definition and location internationally. Some are regional allergies such as mustard allergy in France or royal jelly allergy in Hong Kong.
    A recent metaanalysis of international studies showed there is a large difference between self-reported and challenge-proven prevalence.

    Prevelence of food allergies. All numbers are percentages.

    Food		Self reported	Challenge-proven
    Milk		1.2-17		0-3
    Egg		0.2-7		0-1.7
    Peanut		0-2		0.2-1.6
    Any food 	3-35		1-10.8
    

    Overall, egg and milk are the most common food allergies.
    In children, egg, milk, soy, wheat and peanut allergies predominate.
    In adults, crustaceans, tree nuts, peanuts and fish predominate.

    Questions for Further Discussion
    1. How can children with severe food allergies be accommodated in the lunch room at school?
    2. How can airplane flights be made safer for patients with severe food allergies?
    3. Up to what age can exclusive breast feeding prevent or delay atopic dermatitis, cow milk allergy and wheezing?

    Related Cases

    To Learn More
    To view pediatric review articles on this topic from the past year check PubMed.

    Evidence-based medicine information on this topic can be found at the National Guideline Clearinghouse and the Cochrane Database of Systematic Reviews.

    Information prescriptions for patients can be found at MedlinePlus for these topics: Allergy and Food Allergy and at Pediatric Common Questions, Quick Answers for this topic: Milk Allergy

    .

    To view current news articles on this topic check Google News.

    To view images related to this topic check Google Images.

    Rona RJ, Keil T, Summers C, Gislason D, Zuidmeer L, Sodergren E, Sigurdardottir ST, Lindner T, Goldhahn K, Dahlstrom J, McBride D, Madsen C.

    The prevalence of food allergy: a meta-analysis.
    J Allergy Clin Immunol. 2007 Sep;120(3):638-46.

    Kurowski K, Boxer RW.
    Food allergies: detection and management.
    Am Fam Physician. 2008 Jun 15;77(12):1678-86.

    Lack G.
    Epidemiologic risks for food allergy.
    J Allergy Clin Immunol. 2008 Jun;121(6):1331-6.

    Zuidmeer L, Goldhahn K, Rona RJ, Gislason D, Madsen C, Summers C, Sodergren E, Dahlstrom J, Lindner T, Sigurdardottir ST, McBride D, Keil T.
    The prevalence of plant food allergies: a systematic review.
    J Allergy Clin Immunol. 2008 May;121(5):1210-1218.e4.

    ACGME Competencies Highlighted by Case

  • Patient Care
    1. When interacting with patients and their families, the health care professional communicates effectively and demonstrates caring and respectful behaviors.
    2. Essential and accurate information about the patients’ is gathered.
    4. Patient management plans are developed and carried out.
    5. Patients and their families are counseled and educated.
    7. All medical and invasive procedures considered essential for the area of practice are competently performed.
    8. Health care services aimed at preventing health problems or maintaining health are provided.
    9. Patient-focused care is provided by working with health care professionals, including those from other disciplines.

  • Medical Knowledge
    10. An investigatory and analytic thinking approach to the clinical situation is demonstrated.
    11. Basic and clinically supportive sciences appropriate to their discipline are known and applied.

  • Interpersonal and Communication Skills
    17. A therapeutic and ethically sound relationship with patients is created and sustained.
    18. Using effective nonverbal, explanatory, questioning, and writing skills, the healthcare professional uses effective listening skills and elicits and provides information.
    19. The health professional works effectively with others as a member or leader of a health care team or other professional group.

  • Systems Based Practice

    26. Partnering with health care managers and health care providers to assess, coordinate, and improve health care and how these activities can affect system performance are known.

    Author
    Donna M. D’Alessandro, MD
    Professor of Pediatrics, University of Iowa Children’s Hospital

    Date
    October 20, 2008

  • What Is The Differential Diagnosis of Hepatomegaly?

    Patient Presentation
    A 9-year-old male came to clinic with fever and stomachache. His rapid strep was positive and he was treated with penicillin.
    Three weeks later he complained of abdominal pain again, accompanied by a low-grade fever, some nausea, early satiety and mild fatigue.
    He had no sore throat, diarrhea, changes in bowel or urinary patterns, upper respiratory symptoms, or rashes.
    Some of his friends had colds, and he had no pet exposure or travel history.
    The past medical history showed a healthy male.
    The review of systems revealed no night sweats, weight loss, pruritus, jaundice, bleeding, bruising, or other pain.
    The pertinent physical exam showed a slightly tired male in no distress. His temperature was 38.2° Celsius, he had a 1 pound weight loss from the previous visit, but the rest of the vital signs were normal.
    HEENT showed no icterus and some anterior cervical nodes that were <0.5 cm. He had no other lymphadenopathy.
    His abdominal examination showed fullness of the right side of the abdomen and a liver edge that was 2-3 cm above the umbilicus and crossing the midline. He had no splenomegaly, other palpable masses or ascites.
    He had no skin changes including prominent vessels.
    The radiologic evaluation of right upper quadrant ultrasound found a large heterogeneous mass in the right lobe of the liver.
    The patient was transferred to a regional children’s hospital for further evaluation where a CT scan confirmed the diagnosis.
    He was taken to the operating room where a resection of the right lobe of the liver and mass was completed.
    Anatomic pathology reported a diagnosis of embryonal cell sarcoma with tumor free surgical margins and negative abdominal lymph node biopsies.
    The laboratory evaluation included liver function tests, hepatitis panel, alpha-fetoprotein levels, human chorionic gonadotropin levels, carcinoembryonic antigen, and routine cancer markers. All were negative.
    The patient’s clinical course post-operatively was uneventful and he was begun on chemotherapy.


    Figure 67 – Axial image from an ultrasound exam of the
    liver shows a large inhomogenous mass in the right lobe of the liver.
    The mass is primarily hyperechoic in appearance, with multiple
    hypoechoic regions within it.


    Figure 68 – A coronal two dimensional reconstruction
    delayed phase image of the liver from a computed tomography exam of
    the abdomen performed with oral and intravenous contrast. A large
    lesion, measuring 12 cm in diameter, is seen in the right lobe of the
    liver. There is peripheral vascular enhancement of the mass, which
    has a primarily necrotic center. Differential diagnosis included
    hepatoblastoma, hepatocellular carcinoma, and embryonal sarcoma.

    Discussion
    Liver masses in children include primary liver cancer, metastatic cancer from other sites, cysts and inflammatory masses.
    Primary liver cancer only constitutes 1-2% of all pediatric malignancies.

    Primary liver malignancies in infants and young children usually are caused by hepatoblastoma. In older children hepatocellular carcinoma is the most common.
    For intermediate ages both are common along with transitional cell tumors and primary sarcomas. Other malignant liver tumors include angiosarcoma, biliary rhabdomyosarcoma, undifferentiated sarcomas and rhabdoid tumor.
    Benign liver tumors include adenoma, focal nodular hyperplasia, infantile hemangioma, mesenchymal hamartoma and teratoma.

    Primary hepatic sarcoma is rare with the outcome depending on tumor resection, sensitivity to chemotherapy and/or radiotherapy and tumor histology.
    In a study of 30 patients with primary liver sarcomas, 11 had resection plus chemotherapy. The overall actuarial 5 year survival was 70%. Those with embryonal sarcoma had an actuarial 5 year survival of 80%.

    Learning Point
    On physical examination, normal liver size is &lt; 3.5 cm below the right costal margin for newborns and < 2.0 cm for older children.
    A normal liver span for a newborn is ~4.5-5 cm and at 12 years of age is 6-6.5 cm for females and 7-8 cm for males. In between these times there should be appropriate linear growth with the child.

    Hepatomegaly is caused by inflammation, infiltration, obstruction, storage abnormalities and vascular congestion.
    The differential diagnosis of hepatomegaly includes:

    • Inflammation
      • Autoimmune disease
      • Bile acid enzyme defects
      • Canalicular bile acid transport defects
      • Infections – virus, abscess
      • Idiopathic neonatal hepatitis
      • Kupffer cell hyperplasia – granulomatous hepatitis, sepsis, vitamin A toxicity
      • Medications
      • Toxins
    • Infiltration
      • Cysts – choledochal, parasitic, polycystic liver disease
      • Extramedullary hematopoiesis – erythroblastosis fetalis
      • Hemophagocytic syndromes
      • Primary liver tumors – malignant and benign, as above
      • Metastatic liver tumors – histiocytosis, leukemia, lymphoma, neuroblastoma, Wilm’s
    • Obstruction
      • Biliary atresia
      • Cholelithiasis
      • Choledochal cyst
      • Liver tumors
    • Storage abnormalities
      • Fat – cystic fibrosis, diabetes, fatty acid oxidation defect, malnutrition, mucopolysaccharidoses, parenteral nutrition, Reye syndrome
      • Glycogen – diabetes, glycogen storage disease, parenteral nutrition
      • Lipid – Gaucher disease, Neimann-Pick disease, Wolman disease
      • Metal – hemochromtosis (iron), porphyria (heme), Wilson disease (copper)
      • Protein – alpha-1-antitrypsin deficiency, amyloidosis, carbohydrate-glycoprotein deficiency
    • Vascular congestion
      • Budd-Chiari syndrome (hepatic vein thrombosis)
      • Congestive heart failure
      • Pericardial disease (restrictive)
      • Suprahepatic web of the IVC.
      • Veno-occlusive disease

    Questions for Further Discussion
    1. What other organs can cause factitious enlargement of the liver?
    2. What laboratory testing should be considered for initial evaluation of hepatomegaly?
    3. What are the indications for liver transplantation?

    Related Cases

    To Learn More
    To view pediatric review articles on this topic from the past year check PubMed.

    Evidence-based medicine information on this topic can be found at the National Guideline Clearinghouse and the Cochrane Database of Systematic Reviews.

    Information prescriptions for patients can be found at MedlinePlus for this topic: Liver Cancer

    To view current news articles on this topic check Google News.

    To view images related to this topic check Google Images.

    Wolf AD, Lavine JE.
    Hepatomegaly in neonates and children.
    Pediatr Rev. 2000 Sep;21(9):303-10.

    Rudolph CD, et.al. Rudolph’s Pediatrics. 21st edit. McGraw-Hill, New York, NY. 2003:1478.

    Meyers RL.
    Tumors of the liver in children.
    Surg Oncol. 2007 Nov;16(3):195-203.

    Weitz J, Klimstra DS, Cymes K, Jarnagin WR, D’Angelica M, La Quaglia MP, Fong Y, Brennan MF, Blumgart LH, Dematteo RP.
    Management of primary liver sarcomas.
    Cancer. 2007 Apr 1;109(7):1391-6.

    ACGME Competencies Highlighted by Case

  • Patient Care
    1. When interacting with patients and their families, the health care professional communicates effectively and demonstrates caring and respectful behaviors.
    2. Essential and accurate information about the patients’ is gathered.
    3. Informed decisions about diagnostic and therapeutic interventions based on patient information and preferences, up-to-date scientific evidence, and clinical judgment is made.
    4. Patient management plans are developed and carried out.
    7. All medical and invasive procedures considered essential for the area of practice are competently performed.
    9. Patient-focused care is provided by working with health care professionals, including those from other disciplines.

  • Medical Knowledge
    10. An investigatory and analytic thinking approach to the clinical situation is demonstrated.
    11. Basic and clinically supportive sciences appropriate to their discipline are known and applied.

  • Practice Based Learning and Improvement
    13. Information about other populations of patients, especially the larger population from which this patient is drawn, is obtained and used.
    14. Knowledge of study designs and statistical methods to appraisal clinical studies and other information on diagnostic and therapeutic effectiveness is applied.

    Author
    Donna M. D’Alessandro, MD
    Professor of Pediatrics, University of Iowa Children’s Hospital

    Date
    October 13, 2008

  • Curators Note: Evidence-based Medicine Information Added to Each Case

    Beginning October 6, 2008, each case in PediatricEducation.org will now include evidence-based medicine information in the To Learn More section.

    The National Guideline Clearinghouse is an automated search on the case topic.
    The Cochrane Database of Systemic Reviews does not allow automated searching so a link to its main search page is used instead.

    We hope you find this new feature helpful.
    Donna M. D’Alessandro, M.D. and Michael P. D’Alessandro, M.D.
    Curators, PediatricEducation.org