1. Connective tissue diseases: A focus on lupus and sclerosing disorders
Alisa Femia, MD
Assistant Professor
Director of Inpatient Dermatology Ronald O. Perelman Department of Dermatology
New York University School of Medicine
September 23, 2016 1

2. 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 includes discussion of off-label use of medications

3. Case 1

4. Acute Cutaneous Lupus Erythematosus (ACLE)
Often confused with:
Erythrotelangiectatic rosacea
Seborrheic dermatitis
Dermatomyositis
Drug or viral eruption (especially when generalized)
Broader Ddx: Contact dermatitis, flushing disorders

5. Acute Cutaneous Lupus Erythematosus (ACLE)
Clinical Clues:
Spares the nasolabial folds
Often associated alopecia, particularly of the frontal scalp
May have peri-oral hemorrhagic crusting
Relatively fixed
Generalized ACLE often involves areas that are protected from the sun

6. Acute Cutaneous Lupus Erythematosus (ACLE)
What percentage of patients with the “butterfly rash” have or will develop SLE?

7. Acute Cutaneous Lupus Erythematosus (ACLE)
What percentage of patients with the “butterfly rash” have or will develop SLE?
Virtually 100%

8. Acute Cutaneous Lupus Erythematosus (ACLE)
What percentage of patients with the “butterfly rash” have or will develop SLE?
Virtually 100%
May occur prior to symptoms of SLE
Flares tend to parallel SLE activity

10. Pearls Malar rash has characteristic clinical features
Generalized acute cutaneous lupus can involve non-photoexposed sites
Associated with SLE in virtually 100%

11. Case 2

12. Discoid Lupus Erythematosus
PASTED
P – follicular Plugging
A – atrophy
S – scale
T – telangiectasia
E – erythema
D - dyspigmentation

13. Discoid Lupus Erythematosus
PASTED
P – follicular Plugging
A – atrophy
S – scale
T – telangiectasia
E – erythema
D - dyspigmentation

14. 43 patients with CLE treated with MTX
31 refractory to anti-malarials
12 refractory to additional agents
Improvement in 98%

15. Therapeutic Ladder Photoprotection Smoking cessation
Topicals, intralesional triamcinolone

16. Therapeutic Ladder Photoprotection, smoking cessation, local therapy
Antimalarial therapy
Alone or in combination

17. Antimalarials
Hydroxychloroquine
Chloroquine

18. Antimalarials
Hydroxychloroquine
Chloroquine
Quinacrine

19. Therapeutic Ladder Photoprotection, smoking cessation, local therapy
Antimalarial therapy
Methotrexate

20. Therapeutic Ladder Photoprotection, smoking cessation, local therapy
Antimalarial therapy
Methotrexate
Mycophenolate mofetil, belimumab, azathioprine, IVIG, acitretin/isotretinoin, dapsone, thalidomide, lenalinomide

21. Therapeutic Ladder Photoprotection, smoking cessation, local therapy
Antimalarial therapy
Methotrexate
Mycophenolate mofetil, belimumab, azathioprine, IVIG, acitretin/isotretinoin, dapsone, thalidomide, lenalinomide

22. Therapeutic Ladder Photoprotection, smoking cessation, local therapy
Antimalarial therapy
Methotrexate
Mycophenolate mofetil, belimumab, azathioprine, IVIG, acitretin/isotretinoin, dapsone, thalidomide, lenalinomide

23. Thalidomide R.E.M.S (Risk Evaluation and Mitigation Strategy) program
Prescriber and pharmacy certify with Celgene REMS program
Patients sign a patient-physician agreement form
Pregnancy testing for women
Present in semen of males

24. Discoid lupus erythematosus (DLE)
What percentage of patients will be ANA positive?

25. Discoid lupus erythematosus (DLE)
What percentage of patients will be ANA positive?
Roughly 35%

26. Discoid lupus erythematosus (DLE)
How many patients with DLE will develop SLE?

27. Risk of subsequent diagnosis of SLE in DLE patients = 17%27

28. Discoid lupus erythematosus (DLE)
How many patients with DLE will develop SLE?
Roughly 15-20%

29. ç DLE in children less common than in adults
Equal sex distribution prior to puberty
Higher progression to SLE

32. Pearls DLE is scarring, treat early
Higher risk of progression to SLE than previously thought
Low threshold for antimalarials
Often require escalation beyond antimalarials

33. Case 3

34. Chronic Cutaneous Lupus
Suspect lupus panniculitis with any substantial contour change
Involves fatty areas (cheeks, upper outer arms, hips, thighs)
Lupus profundus = DLE overlying lupus panniculitis

35. Lupus Panniculitis Erythema Nodosum
Face, upper outer arms, hips, thighs
Lobular panniculitis
Permanent contour change
Chronic
Anterior lower legs
Septal panniculitis
Non-scarring
Usually self-resolving

36. Lupus Mastitis
Carducci M, et al. J Eur Acad Dermatol Venereol. 2005;19(2): Dandinoglu T, et al. Orthop Muscul Syst. 2014;3(1).
Fernández-Torres R, et al. J Am Acad Dermatol. 2009;60(6): Rosa M, et al. Ann Diagn Pathol. 2013;17(2):230-3.

38. Pearls Lupus panniculitis is a scarring lobular panniculitis
Can affect the breasts as well (mimics malignancy)
Consider filler therapy only once disease quiescence has been ascertained

39. Case 4

40. SQ panniculitis-like T-cell lymphoma
Rare TCL with predilection for SQ tissue
Can clinically and histologically mimic lupus panniculitis
19% have associated autoimmune disease
Most commonly SLE

41. Diffuse MxA staining correlated with LEP
Endothelial staining also correlated with LEP
Minimal MxA staining correlated with SPTCL

42. Pearls
Maintain high suspicion for LEP that fails to respond to therapy -> incisional biopsy
SPTL often associated with autoimmune disease

43. Case 5

44. Subacute Cutaneous Lupus
Approximately 50% associated with SLE
Anti-Ro positive 60-90%, highly photo-sensitive!
Heals with dyspigmentation, not scarring

45. Approximately 30% of SCLE cases are drug-induced
Terbinafine, HCTZ, proton-pump inhibitors
Anti-TNF-α

46. Neonatal Lupus Skin involvement most frequent manifestation
Cardiac involvement in roughly 65%
Hepatobiliary, hematologic involvement

47. 63% required pacemakers
19% mortality
82% detected prior to 30 weeks gestational age

48. Pearls Subacute cutaneous lupus is highly photosensitive
Psoriasiform and annular subtypes
Anti-Ro positive patients must obtain fetal echocardiograms

49. Case 6

50. Pediatric Morphea AKA “localized scleroderma”
Linear morphea is most common variant
Often involves deeper structures
Risk for permanent contractures and functional disability
Often lacks erythema – do not undertreat!

51. Linear morphea: 52% Undergrowth of the extremity: 33%
Contractures: 26%

52. 56% with permanent sequelae
Limited range of motion
Deep atrophy
Limb-length discrepancy
Joint contractures

55. Extremity Linear Morphea: Therapy
Topical therapy: 55 55

56. Extremity Linear Morphea: Therapy
Topical therapy:
Only adjunctive, not used alone 56 56

57. Extremity Linear Morphea: Therapy
Overlying a joint and/or changing rapidly:
MTX 1mg/kg (up to 25mg/week)
Prednisone 1mg/kg, ~3-6 months taper
Not overlying joint:
Consider MTX without prednisone
Second line:
Mycophenolate mofetil (adults 1.5gm BID, children 600mg/m2 BID) 57 57

58. Craniofacial Morphea
Includes “Parry-Romberg” Syndrome, en coup de sabre (ECDS)
Potential sequelae
Neurologic, ophthalmologic, dental
Cosmetic disfigurement

59. Therapy: Craniofacial Morphea/PHA
IV methylprednisolone 30mg/kg qweekly x 12 weeks
MTX 1 mg/kg/week (up to 25mg/week)
Often given IV along with methylprednisolone
Second line if fail MTX is mycophenolate mofetil
Topicals only adjunctive 59 59

60. Pearls
Linear morphea of the extremities is associated with functional limitation, treatment with methotrexate +/- prednisone
Craniofacial morphea is associated with severe disfigurement, treatment with IV methylprednisolone + methotrexate

61. Pearls
Hemifacial atrophy may present with early inflammatory erythema mimicking port-wine stain
Atrophy appears worse as child grows even once disease quiescent, counseling at onset is imperative
Aggressive therapy necessary to limit disfigurement

62. Case 7

63. Adult-onset Linear Morphea
61 patients
Mean delay in diagnosis 27 months
44% functional limitations
Severe cosmetic disfigurement

64. Adult-onset Linear Morphea
With methotrexate:
Resolution more likely (29% vs. 4%)
Progression and recurrence less likely

65. Pearls
Functional limitations are common with adult-onset linear morphea
Treatment algorithm similar to pediatric-onset morphea

66. Case 8

67. Systemic Sclerosis “Puffy hand” sign is often earliest clue
Look for Raynaud’s and nailfold capillary changes

68. Phosphodiesterase inhibitors,
Treatment options
Immuno-
modulators
Vascular
modulators
Anti-fibrotic
medications
Cyclophosphamide
Corticosteroids
MTX
MMF
IVIG,
etc.
CCB’s
ACE-I’s
Phosphodiesterase inhibitors,
etc.
D-penicillamine
Imatinib
ECP
Phototherapy

69. 25 patients with recent onset diffuse cutaneous systemic sclerosis
Statistically significant decrease in modified Rodnan Skin Score and Body Surface Area of involvement
Slow onset – typically still with worsening for 6 months
PFT’s stabilized

70. Eosinophilic Fasciitis
Edema, tightening of extremities
Often confused with systemic sclerosis but distinguish by lack of distal fingertip involvement, nailfold capillary changes
Raynaud’s also typically absent

71. Evaluated prednisone monotherapy, hydroxychloroquine(HCL) monotherapy, and combination therapy
25 had partial to complete response to prednisone, 6 to HCL monotherapy, and 4 to combination therapy

72. Retrospective review between 1995 and 2014 at three academic centers
1,626 patients, 63 with confirmed eosinophilic fasciitis

73. Pearls
Clinical history and physical examination will help distinguish SSc and EF
Early diagnosis and intervention essential
MMF may be helpful for cutaneous involvement in SSc
Systemic steroids + MTX seems to improve patient outcomes in EF

74. Thank you!