Skin Signs of Systemic Disease Blank Childrens Conference Kristen - PDF document

Skin Signs of Systemic Disease Blank Children’s Conference Kristen E. Holland, MD Learning Objectives • Recognize skin findings that suggest a systemic disease • Choose the appropriate tests to make a timely diagnosis • Understand when to obtain consultation from a pediatric dermatologist Case #1 1

History • PMH: healthy • Meds: multivitamin • All: Bactrim and Augmentin cause hives. • SH: lives with parents, no siblings, K4 • FH: MGF with rheumatoid arthritis • ROS: Cough and sore throat due to strep pharyngitis 2 months ago Laboratory Results Abnormal Normal • ANA = 1:160 (<40) • CBC • CK = 983 IU/L (24-175) • ESR • Aldolase = 20.9 U/L (3.4-8.6) • CRP • LDH = 1050 IU/L (425-975) • GGT • AST = 115 IU/L (23-58) • ALT = 37 IU/L (6-35) • MRI Pelvis: extensive multifocal muscle edema without atrophy Juvenile Dermatomyositis • Autoimmune inflammatory disease that affects skin and skeletal muscles – Proximal muscle weakness • Female predominance • Mean age of onset at 7-years-old • No association with malignancy 2

Other Features • Nondestructive, asymmetric arthritis • Dysphagia • Vasculopathy of GI tract  ulceration or hemorrhage • Interstitial lung disease • Cardiac conduction defects Amyopathic Dermatomyositis • Rare variant with cutaneous disease only Classic Rash n = 46 Symptomatic Asymptomatic n = 26 n = 20 Clinically Weak on exam amyopathic n = 10 n = 10 Hypomyopathic Amyopathic n = 8 n = 2 Oberle EJ, Bayer ML, Chiu YE, Co DO. Pediatr Dermatol 2017;34:50-57. 3

Fatigue is Most Common Symptom Clinically All JDM Muscle Symptoms Amyopathic (n=46) (n=10) Weakness 26 (57%) 0 Fatigue 31 (67%) 3 (30%) Dysphagia 6 (13%) 0 Shortness of 4 (9%) 0 Breath Change in Voice 5 (11%) 0 Oberle EJ, Bayer ML, Chiu YE, Co DO. Pediatr Dermatol 2017;34:50-57. Physical Exam is Unreliable 10 CADM Patients Patient AST ALT CK LDH Aldolase MRI 1 ̶ ̶ ̶ + ̶ + 2 + + ̶ + + + 6/10: 3 ̶ ̶ + ̶ ̶ NA ↑ muscle – 4 ̶ ̶ ̶ + ̶ enzymes – 6 ̶ ̶ + - + – 7 + + ̶ + ̶ 2/10: 8 ̶ ̶ ̶ ̶ ̶ + abnormal MRI 9 ̶ ̶ ̶ ̶ ̶ + – 5 ̶ ̶ ̶ ̶ ̶ – 10 ̶ ̶ ̶ ̶ ̶ Oberle EJ, Bayer ML, Chiu YE, Co DO. Pediatr Dermatol 2017;34:50-57. Sensitivity Increases with Testing of More Muscle Enzymes Sensitivity Enzyme(s) tested (n=44) AST 64% ALT 59% CK 61% LDH 68% Aldolase 77% CK + Aldolase 84% All five labs 95% Oberle EJ, Bayer ML, Chiu YE, Co DO. Pediatr Dermatol 2017;34:50-57. 4

Management • Work-up – Muscle enzymes (CK, aldolase, LDH, AST, ALT) – ANA, ESR, CRP • Referral to Dermatology and Rheumatology – Skin biopsy – MRI of proximal muscles – EMG – Muscle biopsy Management • Treatment – Sun avoidance – Corticosteroids + methotrexate are first line – Adjunctive therapy • Topical corticosteroids • Hydroxychloroquine JDM: Summary • Often misdiagnosed as eczema but look for Gottron’s papules • Ask about fatigue and check muscle enzymes 5

Case #2 History • PMH: healthy • Meds: none • All: NKDA • FH: PGM with psoriasis, MA with inflammatory bowel disease, sister with asthma • SH: lives with parents and 18 yo sister, 7 th grade • ROS: negative Morphea (Localized Scleroderma) • Distinct from systemic sclerosis • Autoimmune fibrosing disease of the skin – Insidious and slowly progressive – Delay in presentation and diagnosis • Equal incidence in adults and children • Caucasian and female predominance 6

Classification • Circumscribed (plaque) – Superficial – Deep • Linear – Trunk/limb variant – Head variant • En coup de sabre • Parry-Romberg • Generalized • Pansclerotic • Mixed Neurologic Manifestations • Occurs in 20-40% • Most common when head is involved • Signs and symptoms – Headaches – Seizures – Neuropathy – Asymptomatic MRI abnormalities CHW Experience 32 patients with head involvement 21 patients had neuroimaging Abnormal MRI N = 4 (19%) T2 hyperintensities most common Abnormal MRI Abnormal MRI Normal MRI No symptoms Neuro symptoms Neurologic symptoms N = 2 N = 2 N = 7 Neurologic symptoms N = 9 (28%) Seizures and headaches most common Chiu et al, Pediatr Dermatol , 2012. 7

Musculoskeletal Manifestations • Occurs in 20-50% • Most common with linear morphea on limbs • Signs and symptoms – Arthralgias – Arthritis – Joint contracture – Limb length and girth discrepancy – Functional limitations Risk Factors for Extracutaneous Manifestations Risk of Extracutaneous Odds Ratio p- Manifestations (95% CI) value Linear morphea 38% 22.3 0.0035 (2.8 – 178) Circumscribed morphea 3% Age of onset < 10 years 36% 10.0 0.0036 (2.1 – 47.6) Age of onset ≥ 10 years 5% Pequet et al, Br J Dermatol , 2014. Management • Serologic screening is not indicated or helpful • Referral to Dermatology or Rheumatology – MRI brain with linear involvement of the head • Treatment – Topicals for mild disease – Corticosteroids+methotrexate for moderate- severe disease 8

Morphea: Summary • Linear morphea and young age are risk factors for extracutaneous involvement • Timely diagnosis and treatment are essential to prevent complications Case #3 History • PMH: seasonal allergies, psoriasis • Meds: levocetirizine, desonide ointment • All: NKDA • FH: MGM with ulcerative colitis • SH: lives with mother, stepfather, and sister; 5 th grade • ROS: negative 9

Laboratory Results • Lip biopsy showed non-caseating granulomas Orofacial Granulomatosis • Lip and facial swelling • Mean age of onset at 11-years-old • Non-caseating granulomas on biopsy • Chronic course with recurrent attacks • Male and Caucasian predominance Subtype of Crohn’s Disease • 40.4% have Crohn’s disease – 19.6% at presentation – 20.8% during follow-up • 13.1 ± 11.6 mo • 6.4% have family history of Crohn’s disease Lazzerini et al, World J Gastroenterol , 2014. 10

Patient Course • Negative endoscopy and colonoscopy, declined MRE • Developed oral ulcers • 4 years later – Elevated fecal calprotectin – Repeat endoscopy and colonoscopy showed patchy inflammation but no granulomas Associated Features • Intraoral involvement in 48% – Oral ulcers – Gingival hyperplasia or hyperemia – Cobblestoning • Perioral involvement in 21% – Angular cheilitis – Perioral swelling • Perianal disease in 12% Lazzerini et al, World J Gastroenterol , 2014. Management • Referral to Dermatology and Gastroenterology – Lip biopsy – Work-up for GI disease • Treatment – Topical, intralesional, and oral steroids – Treatment of underlying Crohn’s disease 11

OFG: Summary • Manifestation of mucocutaneous Crohn’s disease • Screen and monitor for GI disease Case #4 History • PMH: healthy • Meds: hydrocortisone cream for rash • All: NKDA • SH: lives with mom and older sister (father not involved), 5 th grade • FH: thyroid disease in maternal aunt and grandmother. Eczema, asthma, and allergies in maternal uncle. Stroke in maternal grandfather. • ROS: negative 12

Laboratory Results Abnormal Normal • ANA = 1:1280 (speckled) • CBC • (+) anti-dsDNA, anti-Sm, • BUN and Cr anti-RNP • Urinalysis • C3 = 49.4 mg/dL (84-168) • CRP • C4 < 6.0 mg/dL (13-44) • (-) anti-SSA, anti-SSB • AST = 129 IU/L (16-46) • ALT = 184 IU/L (6-35) • ESR = 45 mm/hr (0-10) Systemic Lupus Erythematosus • Disease course – Developed arthritis and myositis – Class III lupus nephritis • Started on systemic steroids (IV and oral), hydroxychloroquine, and mycophenolate mofetil Systemic Lupus Erythematosus • Multi-organ autoimmune disease • More severe disease in children than adults • More common in females and Asian, black, and Latino patients 13

SLICC Classification Criteria • Clinical criteria • Immunologic criteria – Acute cutaneous lupus – ANA – Chronic cutaneous lupus – Anti-dsDNA – Nonscarring alopecia – Anti-Sm – Oral or nasal ulcers – Antiphospholipid antibodies – Joint disease – Low complement – Serositis – Direct Coombs’ test – Renal involvement – Neurologic involvement – Hemolytic anemia, leukopenia, lymphopenia, or thrombocytopenia Cutaneous LE • May be part of SLE or seen in isolation • 3 main types – Acute cutaneous LE (ACLE) – Subacute cutaneous LE (SCLE) – Chronic cutaneous LE (CCLE) Cutaneous LE • Children more likely to have lower extremity involvement • Isolated cutaneous LE is uncommon in children – 80% of SCLE had concomitant SLE • 20% of DLE progresses to SLE – May have milder phenotype Dickey BZ et al, Br J Dermatol , 2013. Arkin LM et al, J Am Acad Dermatol , 2015. 14

Management • Extent of initial work-up is controversial – CBC, CMP – ANA, anti-dsDNA, anti-SSA, anti-SSB, anti-Sm, anti-RNP – Complement levels – Antiphospholipid antibodies – Direct Coomb’s test – Urinalysis • Referral to Dermatology and Rheumatology Management • Treatment – Sun avoidance – Hydroxychloroquine – Topical steroids as adjunct • Treat SLE if present Lupus: Summary • Patients with SLE can present with cutaneous complaints • Have a high index of suspicion for SLE in cases of cutaneous LE 15

Case #5 History • PMH: full-term, NSVD, no pregnancy complications • Meds: none • All: NKDA • FH: mom is healthy • SH: lives with mom • ROS: negative Laboratory Results Abnormal Normal • Anti-SSA = 81 U (<5) • CBC • Liver panel • EKG 16