Download Challenging Cases From the Dermatology

Challenging cases from the
Dermatology-Rheumatology Clinic
Alisa Femia, MD
Assistant Professor
Director of Inpatient Dermatology
The Ronald O. Perelman Dept. of Dermatology
NYU Langone Medical Center
September 23, 2016
Disclosures

The content of this presentation does not relate
to any product of a commercial interest;
therefore, there are no relevant financial
relationships to disclose

This presentation will include the discussion of
off-label use of medications
Case 1
Cutaneous Manifestations of
Dermatomyositis
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Pathognomonic
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Heliotrope
Gottron’s papules
Characteristic
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Malar erythema
Photoexposed poikiloderma
Nailfold changes
Scalp disease
Holster sign
Pruritus
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Other
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Ulcerations
Calcinosis (children >
adults)
Mechanic’s hands
Flagellate erythema
Others: vasculitis,
panniculitis, etc.
Dermatomyositis and Malignancy

Population-based data suggests 18-32% of
DM is associated with a malignancy

Malignancy can precede, occur
concomitantly with, or follow DM
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Risk remains elevated for 3-5 years
Sigurgeirsson B, et al. New Engl J Med. 1992;326:363-367.
Chow WH, et al. Cancer causes & control. 1995;6:9-13.
Buchbinder R, et al. Ann Int Med. 2001;134:1087-1095.
Evaluation
Routine and Serum
Studies
• CBC, CMP, TSH, UA,
CA125, CA19-9
• Stool occult blood OR
age-appropriate
colonoscopy
• Women—Papanicolaou
smear
• Yearly physical examination
Radiography
• CT
chest/abdomen/pelvis
• Women – Transvaginal
pelvic ultrasound,
mammography
Evaluation

Repeat annually for 3-5 years!
Pearls

Rely on physical examination to diagnose
cutaneous dermatomyositis

Malignancy strongly associated with
dermatomyositis

Broad screening for malignancy
Case 2
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21% amyopathic, 76% women

10% CADM -> Classic DM
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Incidence:

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Dermatomyositis – 9.63 per million
Clinically amyopathic – 2.08 per million

23% with ILD
 29% skin-predominant, 17% classic
Klein et al. J Am Acad Dermatol. 2007;57(6):938-943.

100 patients

No significant difference in rates of lung
disease in CDM vs. ADM. vs. HDM

No significant difference in rates of
malignancy in CDM vs. ADM vs. HDM
Case 3
Malignancy and JDM
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Malignancy rare in JDM

only 12 cases reported
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Often have findings on physical exam
(hepatosplenomegaly, lymphadenopathy)

Lymphoma most common

No routine screening indicated
Morris, P. & Dare, J. J Pediatr Hematol Oncol. 2010;32:189-191.
Lung disease and JDM

Much less common than in adults

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1 - 4.8% of patients
No formal screening recommendations for
lung disease in JDM
Shah M, et al. Medicine. 2013;97(1):25-41.
Treatment of Calcinosis
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Treat the underlying
disease!
Intralesional
corticosteroids
Diltiazem
Bisphosphonates
Minocycline
Aluminum Hydroxide
Warfarin
Sodium thiosulfate
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TNF-alpha inhibitors
Intravenous
immunoglobulin
Probenecid
Colchicine
Salicylates
Rituximab
Hematopoietic SCT
Surgical Excision
Laser (CO2, Er:YAG)
Pearls

Malignancy and pulmonary screening in
dermatomyositis is warranted regardless of
muscle involvement

No need for malignancy or pulmonary workup in children

Calcinosis common in juvenile
dermatomyositis
Case 4
Dermatomyositis: Role of serology in
evaluation?
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ANA: 15-35%

Jo-1: 5-15%
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Mi-2: 5-15%; highly specific
Dermatomyositis and Autoantibodies
Autoantibody
Clinical associations
Anti-SAE
Skin disease -> muscle disease; dysphagia
Anti-Jo-1
Pulmonary involvement
Anti-Mi-2
Highly specific, classic DM, better prognosis
Anti-CADM140/MDA-5
Clinically amyopathic, rapidly progressive ILD
(Asian literature), ulcerations, palmoplantar
papules
Anti-p155/TIF-1Υ
Malignancy
Anti-MJ/NXP-2
Calcinosis; Malignancy in adult DM
Fujimoto. Ann Rheum Dis. 2013;72:151-153., Sugiura K, et al. JAAD. 2012;64(4):e167-168.,
Tarrgoff IN, Riechlin M. Arthritis Rheum. 185;28)7):796-803., Sato S et al. Mod Rheum. 2012 May 29 [Epub ahead of print];
Targoff IN, et al. Arthritis Rheum. 2006;54(11):3682-3689.)
Dermatomyositis and Autoantibodies
Autoantibody
Clinical associations
Anti-SAE
Skin disease -> muscle disease; dysphagia
Anti-Jo-1
Pulmonary involvement
Anti-Mi-2
Highly specific, classic DM, better prognosis
Anti-CADM140/MDA-5
Clinically amyopathic, rapidly progressive ILD
(Asian literature), ulcerations, palmoplantar
papules
Anti-p155/TIF-1Υ
Malignancy
Anti-MJ/NXP-2
Calcinosis; Malignancy in adult DM
Fujimoto. Ann Rheum Dis. 2013;72:151-153., Sugiura K, et al. JAAD. 2012;64(4):e167-168.,
Tarrgoff IN, Riechlin M. Arthritis Rheum. 185;28)7):796-803., Sato S et al. Mod Rheum. 2012 May 29 [Epub ahead of print];
Targoff IN, et al. Arthritis Rheum. 2006;54(11):3682-3689.)
Dermatomyositis and Autoantibodies
Autoantibody
Clinical associations
Anti-SAE
Skin disease -> muscle disease; dysphagia
Anti-Jo-1
Pulmonary involvement
Anti-Mi-2
Highly specific, classic DM, better prognosis
Anti-CADM140/MDA-5
Clinically amyopathic, rapidly progressive ILD
(Asian literature), ulcerations, palmoplantar
papules
Anti-p155/TIF-1Υ
Malignancy
Anti-MJ/NXP-2
Calcinosis; Malignancy in adult DM
Fujimoto. Ann Rheum Dis. 2013;72:151-153., Sugiura K, et al. JAAD. 2012;64(4):e167-168.,
Tarrgoff IN, Riechlin M. Arthritis Rheum. 185;28)7):796-803., Sato S et al. Mod Rheum. 2012 May 29 [Epub ahead of print];
Targoff IN, et al. Arthritis Rheum. 2006;54(11):3682-3689.)
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376 patients
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Anti-p155/140 (7%) – 68% with malignancy

MDA-5 (11%) – amyopathic DM (77%) and
rapidly progressive ILD (93%)
Y Hamaguchi et al
From: Clinical Correlations With Dermatomyositis-Specific Autoantibodies in Adult Japanese Patients With
Dermatomyositis: A Multicenter Cross-sectional Study
Arch Dermatol. 2011;147(4):391-398. doi:10.1001/archdermatol.2011.52
Anti-Mi2
Anti-p155
Anti-MDA5
Figure Legend:
Cumulative survival rates from the time of diagnosis in 77 Japanese patients with dermatomyositis with serum anti–Mi-2, anti–
155/140, and anti–CADM-140 autoantibodies. Cumulative survival rates were compared using log-rank tests.
Copyright © 2012 American Medical
Association. All rights reserved.
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77 DM patients
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13% anti-MDA5
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67% with anti-MDA5 had ILD
Typical clinical manifestations of patients with anti-MDA5 Ab. The palmar pustules (A) were
mainly located near the MCP and PIP joints (arrows) and multiple ulcer regions (B) were also
observed.
Koga T et al. Rheumatology 2012;51:1278-1284
© The Author 2012. Published by Oxford University Press on behalf of the British Society for
Rheumatology. All rights reserved. For Permissions, please email:
[email protected]
Pearls

Serology can help prognosticate patients
with dermatomyositis

MDA5 associated with amyopathic
dermatomyositis and rapidly progressive
interstitial lung disease

Cutaneous ulcerations and palmar papules
often present in MDA5+ patients
Case 5
Anti-TIF-1Υ
Anti-TIF1Υ
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Psoriasiform patches
“Red on white” patches
Hyperkeratotic papules
Pearls
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Auto-antibodies generally not helpful in
diagnosis of DM
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Anti-TIF1Υ associated with malignancy
even more so than baseline population
with dermatomyotisis
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Psoriasiform patches, red-on-white
patches, hyperkeratotic papules are
cutaneous clue to anti-TIF1Υ
Case 6
Dermatomyositis: Therapy
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Is myositis present?
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Is there internal organ involvement?
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How bothersome is skin disease?
Health-Related Quality-of-life in
Dermatomyositis
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Pilot-test of a novel quality-of-life
measure of dermatomyositis
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Physical comfort, pruritus, and
photosensitivity highly ranked by 60-90%

Impact on quality-of-life more dramatic
than seen in psoriasis and cutaneous
lupus patients
Femia AN, Vleugels RA. Data,
2014.
Cutaneous DM Treatment Ladder
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1) Pruritus
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2) Photoprotection
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Avoid mid-day sun, wide-brimmed hat, tinted car
windows, vitamin D
3) Topicals
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Around-the-clock antihistamines, Sarna lotion
Coticosteroids, tacrolimus
4) Antimalarials
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Alone or in combination
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1/3 of DM patients develop cutaneous
reaction to HCQ
Usually morbilliform
May tolerate alternative antimalarials
Therapeutic Ladder: Cutaneous DM
Photoprotection
Topical
corticosteroids
Topical
calcineurin
inhibitors
Antipruritics
Antimalarials
IVIG
Methotrexate
Mycophenolate
mofetil
Dapsone
Thalidomide
Azathioprine
Rituximab
Calcineurin
inhibitors
Tofacitinib
IVIG for Recalcitrant
Cutaneous Dermatomyositis
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13 patients with refractory cutaneous DM
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8 with complete response
2 with marked response (>75%)
3 with partial response (<75%)
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Corticosteroid-sparing in 6/6 patients
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Minimal side effects (headaches in 2 patients)
IVIG
Immunesuppressants
Steroids
Additional Therapies
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Anti-TNF-α
Leflunomide
Dapsone
Azathioprine
Thalidomide
Sirolimus
Rituximab
Tofacitinib
Hematopoietic stem cell transplant

16 patients; 11 randomized to etanercept, 5 to
placebo
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5 etanercept treated patient had
corticosteroid-sparing
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5 had flares of cutaneous DM
Conclusion

Cutaneous dermatomyositis has a profound
impact on quality-of-life

Methotrexate and IVIG particularly helpful
for refractory cutaneous dermatomyositis

Several additional systemic treatment options
may be beneficial
Case 7
Su, et al. Int J of Dermatol
2004;43:790

240 charts
identified
with a
diagnosis of
PG

95 cases had
definitive
evidence of
alternative
diagnosis
Pearls

Pyoderma gangrenosum is a diagnosis of
exclusion
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Tissue biopsy and tissue cultures warranted
in essentially all cases
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Do not be afraid of pathergy!
Case 8
Pathergy and Pyoderma
Gangrenosum
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Not all patients will exhibit pathergy
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Debridement or other surgical intervention
likely to exacerbate pathergy
Wound Care and PG
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Essential component of therapy

Gentle cleansing with sterile saline or mild
antiseptic prior to dressing changes
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Maintain most environment
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Avoid wet-to-dry dressings, silver nitrate
Pearls

Close collaboration with surgical colleagues
and local wound care centers necessary
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Wound care necessary in healing

Inflammatory response in PG may mimic
sepsis
Case 9
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At least 50% of pyoderma gangrenosum is
associated with systemic disease
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Hematologic malignancy, inflammatory bowel
disease
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At least 50% of pyoderma gangrenosum is
associated with systemic disease
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Hematologic malignancy, inflammatory bowel
disease
Other associations: arthritis, PAPA, PASH,
other autoimmune disorders (ie: systemic
lupus, rheumatoid arthritis), thyroid disease,
metabolic syndrome
Pyoderma Gangrenosum: Work-up
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Thorough history and review of systems
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CBC
CMP
GI evaluation
Serum electrophoresis and immunofixation
ANCA screen
Anti-phospholipid panel
Consider: ANA, rheumatoid factor,
hypercoaguable studies, CXR, hepatitis panels
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Pearls
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Pyoderma gangrenosum is often associated
with systemic disease
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No established treatment algorithm –
consider comorbidities and disease
associations

Prednisone, cyclosporine, infliximab,
dapsone often helpful
Case 10
Past Medical History
- ? SLE
- Hepatitis C
- Levamisole-induced vasculopathy
- IVDU
Past Medical History
- ? SLE
- Hepatitis C
- Levamisole-induced vasculopathy
- IVDU
Labs
-
ANA 1:160, speckled
p-ANCA positive
Neutropenic
Utox + cocaine
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5/6 patients initially misdiagnosed
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Lupus anticoagulant or anti-cardiolipin,
ANA, anti-dsDNA, ANCAs
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Retiform purpura, ear and digit involvement
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Latency 1-4 weeks
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100% lower extremity, 75% multiple site
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All had (+) pANCA and/or (+)
antiphospholipid antibodies, 2 neutropenia
Pearls

Pyoderma gangrenosum may occur as result
of levamisole-adulterated cocaine

Clinical and histologic findings similar to
other forms of pyoderma gangrenosum

Serology can resemble levamisole-associated
vasculopathies
Case 11
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Pyoderma gangrenosum in 1-3% of IBD
patients (UC > CD)
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Sweet’s syndrome less common
Azathioprine-induced Sweet’s
Syndrome
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Generally occurs roughly 2 weeks after
initiation of azathioprine
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May resolve with drug withdrawal alone

On a spectrum with azathioprine-induced
hypersensitivity syndrome
Pearls

Azathioprine-induced SS is easily
overlooked, may mimic other disease-related
dermatoses, sepsis

Differentiate from IBD-associated SS,
pustules or vesicles common in drugassociated SS
Pearls
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Neutrophilic dermatoses overlap clinically
and histologically, cannot rely on biopsy
alone
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Azathioprine-induced SS may resolve with
drug withdrawal alone
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Avoid re-challenge
Questions?