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

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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

2

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

• ANA = 1:160 (<40)
• CK = 983 IU/L (24-175)
• Aldolase = 20.9 U/L (3.4-8.6)
• LDH = 1050 IU/L (425-975)
• AST = 115 IU/L (23-58)
• ALT = 37 IU/L (6-35)

Normal

• CBC
• ESR
• CRP
• GGT
• 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

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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 n = 26 Asymptomatic n = 20 Weak on exam n = 10 Clinically amyopathic n = 10 Hypomyopathic n = 8 Amyopathic n = 2

Oberle EJ, Bayer ML, Chiu YE, Co DO. Pediatr Dermatol 2017;34:50-57.

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Fatigue is Most Common Symptom

Muscle Symptoms All JDM (n=46) Clinically Amyopathic (n=10) Weakness 26 (57%) Fatigue 31 (67%) 3 (30%) Dysphagia 6 (13%) Shortness of Breath 4 (9%) Change in Voice 5 (11%)

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 + + ̶ + + + 3 ̶ ̶ + ̶ ̶ NA 4 ̶ ̶ ̶ + ̶ – 6 ̶ ̶ +

• +

– 7 + + ̶ + ̶ – 8 ̶ ̶ ̶ ̶ ̶ + 9 ̶ ̶ ̶ ̶ ̶ + 5 ̶ ̶ ̶ ̶ ̶ – 10 ̶ ̶ ̶ ̶ ̶ –

2/10: abnormal MRI 6/10: ↑ muscle enzymes Oberle EJ, Bayer ML, Chiu YE, Co DO. Pediatr Dermatol 2017;34:50-57.

Sensitivity Increases with Testing of More Muscle Enzymes

Enzyme(s) tested Sensitivity (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.

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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

6 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, 7th

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

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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

Abnormal MRI No symptoms N = 2 Abnormal MRI Neuro symptoms N = 2 Normal MRI Neurologic symptoms N = 7

32 patients with head involvement 21 patients had neuroimaging

Abnormal MRI N = 4 (19%) T2 hyperintensities most common Neurologic symptoms N = 9 (28%) Seizures and headaches most common

Chiu et al, Pediatr Dermatol, 2012.

8 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 Manifestations Odds Ratio (95% CI) p- value Linear morphea 38% 22.3 (2.8 – 178) 0.0035 Circumscribed morphea 3% Age of onset < 10 years 36% 10.0 (2.1 – 47.6) 0.0036 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

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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; 5th grade

• ROS: negative

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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.

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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

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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), 5th grade

• FH: thyroid disease in maternal aunt and
• grandmother. Eczema, asthma, and allergies

in maternal uncle. Stroke in maternal grandfather.

• ROS: negative

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Laboratory Results

Abnormal

• ANA = 1:1280 (speckled)
• (+) anti-dsDNA, anti-Sm,

anti-RNP

• C3 = 49.4 mg/dL (84-168)
• C4 < 6.0 mg/dL (13-44)
• AST = 129 IU/L (16-46)
• ALT = 184 IU/L (6-35)
• ESR = 45 mm/hr (0-10)

Normal

• CBC
• BUN and Cr
• Urinalysis
• CRP
• (-) anti-SSA, anti-SSB

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

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SLICC Classification Criteria

• Clinical criteria

– Acute cutaneous lupus – Chronic cutaneous lupus – Nonscarring alopecia – Oral or nasal ulcers – Joint disease – Serositis – Renal involvement – Neurologic involvement – Hemolytic anemia, leukopenia, lymphopenia, or thrombocytopenia

• Immunologic criteria

– ANA – Anti-dsDNA – Anti-Sm – Antiphospholipid antibodies – Low complement – Direct Coombs’ test

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.

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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

16 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

• Anti-SSA = 81 U (<5)

Normal

• CBC
• Liver panel
• EKG

17 Neonatal Lupus Erythematosus

• Transplacental passage of anti-SSA(Ro)

antibodies

– Anti-SSB(La) or anti-U1RNP in <5% – Most mothers are asymptomatic

• Average age of onset at 6 weeks
• Self-resolves in 6-12 months with

clearance of maternal antibodies

Spectrum of NLE

• Cutaneous in 16%
• Cardiac

– Prolonged QT interval in 41% – Complete congenital heart block in 1.6%

• Hematologic in 27%

– Anemia – Thrombocytopenia – Neutropenia

• Hepatitis in 26%

Cimaz R et al, J Pediatr, 2003.

Management

• Work-up

– CBC – Liver panel – ANA, anti-SSA, anti-SSB, anti-RNP – EKG

• Monitor abnormal labs

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Management

• Treatment

– Topical steroids for cutaneous manifestations – Pacemaker or cardiac surgery for CCHB

• Counseling

– Risk of future autoimmune disease for child – 25% risk of second affected child

• Mother should be monitored and treated in

subsequent pregnancies

Summary

• Neonatal lupus presents with annular

plaques and/or periorbital involvement

• Evaluate for cardiac, hematologic, or

hepatic involvement

Questions?