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M EDICAL G RANDROUNDS

New season. M EDICAL G RANDROUNDS. Michelle Anne Rosales Ozaeta , MD Department of Internal Medicine FIRST YEAR RESIDENT Fellow In-Charge: Maria Princess M. Landicho , M.D. Moderator : Maria Jocelyn C. Isidro, M.D Resource Speaker: Marysia T. Recto, M.D. Objectives. GENERAL :

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M EDICAL G RANDROUNDS

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  1. New season MEDICAL GRANDROUNDS Michelle Anne Rosales Ozaeta, MD Department of Internal Medicine FIRST YEAR RESIDENT Fellow In-Charge: Maria Princess M. Landicho, M.D. Moderator: Maria Jocelyn C. Isidro, M.D Resource Speaker: Marysia T. Recto, M.D.

  2. Objectives • GENERAL : • Discuss multiple autoimmune disorders in a 19 year old male with alopecia universalis. • Specific : • Discuss a patient with newly diagnosed diabetes mellitus with diabetic ketoacidosis at presentation. • Determine other possible autoimmune diseases that may accompany diabetes mellitus and alopecia universalis. • Explore immunodeficiency as a possible cause of recurrent infections since childhood.

  3. What we theoretically read in books is someone else’s reality.

  4. JMC, 19 yearold male admitted on Oct. 10, 2010 Chief complaint: FEVER and CHILLS

  5. HISTORY OF PRESENT ILLNESS CHILDHOOD Patchy hair loss when he was 10 Diagnosed to have alopecia universalisat 11 of unknown etiology. Bouts of flu-like symptoms every 4-5 months; Pneumonia 1x/year

  6. HISTORY OF PRESENT ILLNESS CHILDHOOD He was admitted at MMC for 8 days and treated as a case of pneumonia Negative AFB smear and culture 2 months

  7. HISTORY OF PRESENT ILLNESS CHILDHOOD 2 months 2 weeks Polyphagia, polydipsia, polyuria, nocturia (+) Generalized weakness, anorexia, undocumented weight loss (+) thirst, nausea, dizziness 5 days Few hours (+) Fever and chills, vomiting Admission

  8. REVIEW OF SYSTEMS

  9. REVIEW OF SYSTEMS

  10. BriefPediatricHistory • Birth/Maternal History: Born to a then 38 year old G2P1 (1001) via Caesarian Section, no complications. No maternal illnesses during pregnancy. • Immunization History: Completely immunized child. (BCG, DPTx3, OPVx3, HepBx3, Measles, MMR) • Nutritional History: Initially breastfed then shifted to formula milk. No food preferences. • Developmental History: At par with age

  11. PAST MEDICAL HISTORY • Bronchial asthma: (last attack in past year) on as needed salbutamol inhaler, no oral/inhaled steroid use • Not known diabetic, non-hypertensive, no thyroid/liver/kidney disease • No cancer • No surgeries/blood transfusion • No history of trauma

  12. FAMILY MEDICAL HISTORY • Hypertension and stroke: father • Endometrial carcinoma, stage 1: mother • Cancer (unrecalled type): paternal grandfather (-) Alopecia (-) Diabetes, asthma, thyroid disease (-) Autoimmune or connective tissue disease (-) Fetal death in-utero or recurrent abortion in the mother

  13. PERSONAL / SOCIAL HISTORY • Second of 2 siblings • Had an active childhood • 2nd year philosophy student • Non smoker, occasional alcoholic drinker • Had ear piercing done 2 years ago • Tattoo on chest painted in August 2010. • Denies illicit drug use, denies sexual contact

  14. PHYSICAL EXAM

  15. PHYSICAL EXAM Awake, weak-looking, slender, ambulatory, tachypneic, speakswith an adult male voice

  16. PHYSICAL EXAM Generalized absence of hair: head, face, axilla, trunk, extremities. Dry skin especially on lower extremities, no hypo-/hyperpigmented skin lesions.

  17. PHYSICAL EXAM Anictericsclerae, pink palpebral conjunctivae, with dry lips, and buccal mucosa, no oral thrush, non hyperemic posterior pharyngeal wall and tonsils, no neck mass, flat neck veins. Equal chest expansion, no retractions, no use of accessory muscles of respiration, clear lungs, no wheezes nor rales Quiet precordium, distinct heartsounds, tachycardic, regularrhythm, no murmurs

  18. PHYSICAL EXAMINATION PHYSICAL EXAM Flat abdomen, normoactivebowelsounds, soft, nontender, no palpable masses, no CVA tenderness Sparsepubichair: Tanner stage 2 Size of penisadequate for age No edema, no cyanosis, pulses full and equal PUBIC HAIR 12-13 yo 13-14 yo 14-15 yo PENIS 15-16yo

  19. PHYSICAL EXAMINATION NEURO EXAM Alert, GCS 15, oriented to 3 spheres Pupils 2mm ERTL Visual acuity 20/25, botheyes Full range of extraocular muscle motions Muscle strength 5/5 all extremities No sensorydeficits Normoreflexive No nystagmus, dysmetria, dysdiadochokinesia No Babinsky

  20. PERTINENT FINDINGS 19 year old male Recurrent respiratory infections Underweight, tachycardic, tachypneic, weak-looking, dehydrated FEVER, CHILLS, VOMITING Polydipsia, polyuria, polyphagia, nocturia, urinary frequency Generalized absence of hair, Sparse pubic hair (tanner 2) Anorexia, weight loss, generalized weakness, nausea, dizziness

  21. COURSE IN THE WARDS

  22. S> fever, chills, urinary frequency occasional nonproductive cough and colds no abdominal pain, no BM changes O> normotensive, tachycardic at 104, RR 22, temp 37.5 no tonsillopharyngeal congestion Clear lungs, nontender abdomen, no CVA tenderness URINALYSIS: Significant pyuria and few-many bacteria, RBC CBC: leukocytosis 14,430, segmenter predominance CHEST XRAY: no infiltrates, no effusion PROBLEM #1 FEVER & CHILLS

  23. IMPRESSION Complicated urinary tract infection PROBLEM #1 Antibiotic coverage: Cefuroxime 750 mg IV q8 Hydration: PNSS 100ml/hour Antiemetic: Metoclopromide 10 mg IV now; Ondansetron drip FEVER & CHILLS BLOOD CS: No growth after 5 days URINE CS: No growth after 2 days

  24. S> Progressing to loss of appetite, malaise, weight loss, vomiting O> BMI 15 CBG = 588 mg/dl URINALYSIS: Sugars 2+, Ketones +2, negative protein SERUM KETONES: 6.6mmol/L HbA1C: 8.5% PROBLEM #2 Polyphagia, polydipsia, polyuria

  25. Diabetic Ketoacidosis OR Hyperglycemic Hyperosmolar State Kitabachi, A., et. Al. 2009. Hyperglycemic crises in adult patients with diabetes. Diabetes Care, 32: 7 (1335-43).

  26. IMPRESSION Diabetic Ketoacidosis, moderate Control of hyperglycemia: Hydration, insulin Monitoring: CBGs, Hydration status (Central line inserted: CVP; accurate I/O), K+ Acidosis: Sodium bicarbonate PROBLEM #2 HYPERGLYCEMIA

  27. GLUCOSE MONITORING DKA acute phase CBG (nth) hour of admission

  28. Input – output monitoring CVPinitial=5-6 CVP =8-10

  29. Serum Sodium Day 1 2 3 4 5 Corrected Na = (RBS - 100) x 0.016 + actual Na

  30. Serum Potassium Day 1 2 3 4 5 6

  31. SERUM CHEMISTRIES

  32. DIABETES

  33. DIABETES Usually develops over a long period of time (months to years) Associated with metabolic syndrome, insulin resistance Harrison’s Internal Medicine 17th ed.

  34. DIABETES • Latent Autoimmune Diabetes of Adults • Slow-onset diabetes or type 1.5 • Form of type 1 diabetes, similar to juvenile diabetes, however, occurs in adults typically over the age of 25.   • Destruction of the pancreas occurring slowly, usually over years. Latent Autoimmune Diabetes in Adults: Symptoms, Diagnosis, Treatment, and Prognosis (http://www.isletsofhope.com/diabetes/symptoms/latent_autoimmune_diabetes_lada_1. html).

  35. DIABETES • Maturity Onset Diabetes of the Young • Age of onset before 25 with an autosomal dominant mode of inheritance (“monogenic diabetes”) with variable penetrance. • Confirmed by specific gene testing • Ineffective insulin production or release by pancreatic β-cells; Mild to moderate hyperglycemia "What is maturity-onset diabetes of the young (MODY)?" (http://www.diabetes.niddk.nih.gov/dm/pubs/mody/#3).

  36. DIABETES • Classic:  polyuria, polydipsia, polyphagia, tiredness, and weight loss. Commonly with DKA as presenting symptom • Polygenic disease, environmental influence, immunologic factors • Autoimmune destruction of pancreatic beta cells, regardless of causative entity. http://www.ncbi.nlm.nih.gov/omim/222100

  37. DIABETES

  38. DIABETES

  39. T1DM SPECIAL TESTS Shivam Champaneri, M.D. and Christopher Saudek, M.D. Autoantibodies in Type 1 Diabetes. 02-03-2011

  40. ALOPECIA UNIVERSALIS • Rapid loss of all hair, including eyebrows and eyelashes. It is the most severe form of alopecia areata *Alopecia Totalis = loss of all scalp hair only • Most cases linked to underlying autoimmune disease, but some cases may be inherited as an autosomal recessive trait (gene HR in 8p21.2). PERSON IN THE PHOTO IS NOT THE PATIENT

  41. Type 1 diabetes : 0.1 to 37 in 100,000 5-10% of all diabetes cases Alopecia universalis: 1 in 100,000 What we already know… PROBLEM #3 RULE OUT OTHER POSSIBLE AUTOIMMUNE DISEASES

  42. PROBLEM #3 RULE OUT OTHER POSSIBLE AUTOIMMUNE DISEASES

  43. PROBLEM #3 RULE OUT OTHER POSSIBLE AUTOIMMUNE DISEASES

  44. Van den Driessche, A,, et al. 2009. Type 1 diabetes and autoimmune polyglandular syndrome: a clinical review. Netherlands J of medicine 67(11): 376-384.

  45. POLYGLANDULAR AUTOIMMUNE SYNDROMES • Different clusters of autoimmune disorders and are rare endocrinopathies characterized by the coexistence of at least two glandular autoimmune mediated diseases • The definition of the syndrome depends on the fact that if one of the component disorders is present, an associated disorder occurs more commonly than in the general population. Kahali. 2010. Polyglandular autoimmune syndromes. European J or Endocrinology 116:11-20.

  46. POLYGLANDULAR AUTOIMMUNE SYNDROMES

  47. POLYGLANDULAR AUTOIMMUNE SYNDROMES • Alopecia • Hypogonadism • Type 1 diabetes • Hypothyroidism • Dental enamel hypoplasia • Malabsorption • Chronic active hepatitis • Vitiligo • Pernicious anemia • Interstitial nephritis • Keratoconjunctivitis Harrison’s Internal Medicine 17th ed.

  48. POLYGLANDULAR AUTOIMMUNE SYNDROMES • Alopecia • Primary hypogonadism • Hypophysitis • Myasthenia gravis • Vitiligo • Pernicious anemia • Celiac disease • Seronegative arthritis • Parkinson’s disease Carpenter'ssyndrome Majeroni, B. 2007. Autoimmune Polyglandular Syndrome Type II. American Family Physician 75(5): 667-670.

  49. POLYGLANDULAR AUTOIMMUNE SYNDROMES vomiting, anorexia, unexplained weight loss, and malaise hyperpigmentation of the skin and mucosal surfaces hypotension, hypoglycemia, and craving for salt Carpenter'ssyndrome Majeroni, B. 2007. Autoimmune Polyglandular Syndrome Type II. American Family Physician 75(5): 667-670.

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