1. Connective Tissue Diseases
Rick Lin, DO MPH

3. Predominant locations of inflammatory infiltrates in subsets of cutaneous lupus erythematosus . The types of cutaneous lupus erythematosus are: acute cutaneous lupus (ACLE), subacute cutaneous lupus (SCLE), chronic cutaneous lupus (CCLE), tumid lupus (TLE), and lupus panniculitis (LEP).The primary locations of the infiltrates are as follows: superficial dermis, ACLE and SCLE; superficial plus deep dermis and periadnexal, DLE; deep dermis, TLE; and subcutaneous fat, LEP.

4. Lupus Erythematosus Chronic Cutaneous LE DLE Verrucous LE
Lichen Planus-LE overlap.
Chiblain LE
Lupus Panniculitis (LE profundus)
With DLE
With Systemic LE

5. Discoid LE Young adults. F:M=2:1
Cat’s Tongue (Langue au chat) = carpet tacks
Lesions heal centrally first with atrophy, scarring, and dyspigmentation
Up to 24% will have mucosal involvement.
95% of cases confine to the skin at the onset and will remain so.

6. Chronic cutaneous lupus erythematosus (CCLE) with discoid lesions
Chronic cutaneous lupus erythematosus (CCLE) with discoid lesions. The ear is a common site of involvement. Note the central depigmentation and scarring. In addition to the obvious, intensely inflamed, indurated lesion on the side of the face, there is a small lesion in the uppermost portion of the concha of the ear.

7. The widespread discoid lesions in this person resulted in depigmentation on the face, arms, and trunk.

8. Discoid LE Spontaneous involution with scarring is common
Progression to SLE is rare and may be identified by abnormal labs.
ANA – elevated
Leukopenia, hematuria, or abuminuria

9. Histology Thinned epidermis Loss of normal rete ridges
Follicular plugging
Hydropic changes of basal layer
Lymphocytic perivascular infiltrate
Increase mucin
DIF is positive more than 75% of case with Igs located at DEJ

10. prominent periadnexal localization.

11. Treatment
SUNSCREEN!!!!
Topical steroid, high potency with occlusion if needed.
Intralesional Injection with Kenalog
Antimalarias: safest and most beneficial system therapy.
Plaquenil for 3 month, if no response switch to Aralen.
If response is still incomplete, change to Quinacrine

12. Verrucous LE AKA hypertrophic LE Resembling KA or hypertrophic LP
Treatment with TAC or Intralesional
Also can be treated with Accutane or Plaquenil.

13. LE-LP Overlap syndrome
Large atrophic hypopigmented bluish-red patches and plaques.
Response to treatment is poor
Dapsone or Accutane maybe effective

14. Chilblain LE
Chronic, unrelenting form of LE with fingertips, rims of ear, calves and heels in women.
Chilblain lesions are due to cold
Usual LE treatment

15. LE Panniculitis AKA LE Profundus Deep subcutaneous nodules 1-4cm
Head, face, and upper arms
Woman age 20-45
Histology shows lymphocytic panniculitis, hyaline degeneration of the fat, hyaline papillary bodies. Over lying epidermis shows hydropic changes and follicular plugging
Treatment with Antimalarials.

17. SCLE Subacute cutaneous LE Papulosquamous Annular
Syndromes commonly exhibiting similar morphology
Neonatal LE
Complement deficiency syndromes

18. SCLE Psoriasiform, polycyclic annular lesions
Shawl distribution: V neck, upper outer and inner arms.
¾ of the patients have arthralgia,
20% have leukopenia
80% have positive ANA
Associated with Ro/SSA and HLA-DR3-Positive.
Hydrochlorothiazide can induce SCLE

19. Subacute cutaneous lupus (SCLE) lesions
Subacute cutaneous lupus (SCLE) lesions. Annular plaques with crusted margins.

20. The lesions on the hands conform to the typical distribution of lupus lesions, sparing the knuckles.

21. SCLE displays a superficial and deep perivascular infiltrate of lymphocytes with interface changes at the epidermis.

22. Neonatal LE Annular scaling erythematous macules and plaques
Appear on head and extremities
First few months of life in babies born to mothers with LE, RA, or other connective tissue disease
Resolve spontaneously by 6 month of age
HALF of the patient has associated congenital heart block, usually 3rd degree

23. Acute Cutaneous LE Characteristic butterfly facial erythema
May last from days to several weeks
Bullous lesion occur as single or grouped vesicle or bullae
Subepidermal bulla containing neutrophils.
HLA-DR2 positive
Minute telangiectases appear in time on the face or elsewhere and commonly appear about the nail folds.
Rowell Syndrome: EM-like lesion dominant in LE

25. Acute cutaneous lupus (ACLE)
Acute cutaneous lupus (ACLE). The patient shown in this photo had ACLE lesions on the arms as well as the face.

26. Systemic LE Young to middle age women
Skin involvement occur 80% of the case
American Rheumatism Association has 11 criteria
If 4 or more of the criteria are satisfied, the patient is said to have SLE

27. ARA SLE criteria Malar Erythema Discoid Lupus Photosensitivity
Oral Ulcers
Arthritis
Serositis
Nephritis
Hematologic
CNS Changes
Immunologic disorder
ANA

29. Systemic Manifestation.
Arthralgia is the earliest abnormality.
95% of SLE patient will have arthralgia.
Avascular necrosis of femoral head.
Thrombosis in vessels secondaary to presence of lupus anticoagulant.
Renal involvement in nephritic or nephrotic type.
Mycocarditis, cardiomegly, EKG changes.

30. Systemic Manifestation.
CNS involvement
Ideopathic throbocytopenic purpura.
Sjorgen’s syndrom
Mixed with dermatomyositis

31. Treatment of SLE
Treatment of depending on the organ system(s) involved.
Skin, musculoskeletal, and serositis-type manifestations generally respond to treatment with hydroxychloroquine and nonsteroidal anti-inflammatory medications.
Porphoria cutaneous tarda may co-exist with LE, in this case, Plaquenil is TOXIC!!!
More serious organ involvement, such as CNS involvement or renal disease, often necessitates immunosuppression with high-dose steroids and cyclophosphamide.

34. Dermatomyositis Gratton's sign - flat-topped violaceous papules
Heliotrope - reddish -purple flush around the eyes
Over knuckle streak erythema
Shawl pattern
Calcinosis Cutis may occur in oer half of the children with DM
Associated with Malignancy

35. Dermatomyositis Symmetrical muscle weakness
assoc c malignant neoplasm when over 40
periungual telangiectasia
Prednisone 60mg until severity decrease. Sunscreen, antimalarial
Mechanics hand: hyperkeratosis, fissuring, scaling involvement in the palm of the hand.

36. Muscle involvement Symmetrical muscle weakness
Unable to raise arms to comb their hair
Cardiac involvement with cardiac failure in terminal phase
Amyopathic dermatomyositis or dermatomyositis sine myositis: DM without muscle changes

37. Violaceous poikiloderma of the face

38. Violaceous poikiloderma of the face, plus thin plaques on the elbows that are sometimes misdiagnosed as psoriasis.

39. Gottron's sign with violaceous poikiloderma over the knuckles.

40. Calcinosis cutis on the abdomen of a child with dermatomyositis

41. Interface dermatitis in biopsy of dermatomyositis .

45. Scleroderma
characterized by symmetric thickening, tightening, and induration of the skin of the fingers and the skin
These changes may affect the entire extremity, face, neck, and trunk (thorax and abdomen).

46. Localized Morphea
Smooth, hard, somewhat depressed, yellowish white, or ivory-colored lesions.
Common on the trunk
Margins surrounded by light violaceous zone or by telangiectases.
Resemble pigskin
Slowly involute over a 3-5 year period.

47. Generalized Morphea Widespread hard indurated plaque.
No systemic involvement
Patient appear young because of the firmness of the skin.
Resolution less likely than the localized version.

48. Early inflammatory plaque type morphea of the trunk

49. Plaque-type morphea of the trunk.

50. Atrophoderma of Pasani and Pierini
Reduction of thickness of derma connective tissue
Upperback and lumbar sacral area
Benign course, usually resolve after few months or few years.
No effect treatment
Variant of morphea.

51. Atrophoderma of Pasini and Pierini
Atrophoderma of Pasini and Pierini. A Multiple depressed, slightly hyperpigmented patches on the back. B Coalescent hyperpigmented patches on the abdomen.

52. Linear Scleroderma Linear lesions extend to length of arms or leg
Begin first decade of life
May also occur parasagitally down the forehead, known as en coup de sabre
Parry-Romberg syndrome: progressive facial hemiatrophy, epilepsy, exophalmos, and alopecia, maybe a form of linear scleroderma.

53. Linear morphea of the leg

54. Morphea en coup de sabre

55. Parry–Romberg syndrome

56. CREST Syndrome AKA Thibierge-Weissenbach Syndrome.
Systemic sclerosis may be limited to the hands, and is called acroslerosis.
Not as severe as PSS
ANA shows anticentromere antibody, and is highly specific.
Most favorable diagnosis

57. Matted telangiectasias

58. Calcinosis cutis of the thumb in a patient with scleroderma

59. Progressive Systemic Sclerosis
Raynaud’s is the first manifestation of PSS most of the time and is eventually nearly always present
Round fingerpad sign: loose the normal peaked contour and appear round from the side.
Pterygium inversum unguis: distal part of nailbed remains adherent to ventral surface of nail plate. Seen also in LE, or congenital

60. Progressive Systemic Sclerosis
75% have dilated nail fold capillary loops
Esophageal involvement in 90% of patients
Pulmonary fibrosis
Cardiac involvement
Articular pain, swelling, polyarthritis.

61. Prognosis Skin involvement after 1 year of diagnosis:
Group I – sclerodactyly alone – 71% 10 year survival rate
Group II - Skin stiffness above metacarpal-phalangeal joints but not involving trunk – 58% survival rate.
Group III – truncal involvement – 21% survival.

62. LAB Finding
Topoisomerase I (formerly Scl–70) is present in 20-30% of patients with diffuse disease (absent in limited disease) and has an increased association with pulmonary fibrosis
Anticentromere antibodies are present in about 60-90% of patients with limited disease and 10-15% with diffuse disease.

63. Histology Increased collagen bundle and thickness of the derma.
Pilosebaceous units are absent. Eccrine glands and ducts are compressed by collagen.
Eccrine glands present at the mid dermis rather than at the junction of dermis/subQ fat.

64. There is a dense sclerosis of the dermis with decreased adnexal structures, and ‘trapping’ of remaining adnexal structures encased by collagen. Sparse perivascular lymphocytes are present.

65. Treatment of morphea and lichen sclerosus
Treatment of morphea and lichen sclerosus. +++ Highly effective; ++,effective +, moderately effective; 0, low efficacy or ineffective. 1, double-blind controlled trials; 2, clinical trial; 3, anecdotal report.

66. Eosinophilic Fasciitis
Patient engaging in strenuous muscular effort few days or week before acute onset of weakness. Follow by severe induration of the skin and subQ tissue of forearms and legs.
Coarse peau d’orange appearance.
Groove sign: depression follow the course of underlying vessles when arms are hold laterally.
Excellent response to corticosteroid.

67. Comparison of deep morphea and eosinophilic fasciitis
Comparison of deep morphea and eosinophilic fasciitis. A Note the ‘pseudo-cellulite’ appearance of the involved skin of the thigh in deep morphea. B In eosinophilic fasciitis, the level of fibrosis is also deep.

68. Histology
Patchy lymphocytic and plasma cell infilrate in the fascia and subfacial muscle and great thickening, times normal of the fascia.

69. Mixed Connective Tissue Disease
Mixed features of scleroderma, SLE, and dermatomyositis
IgG deposition on the Direct IF is a distinctive finding in MCTD
Treatment with daily dose of prednisone 1mg/kg shows good improvement.

70. Sjogren’s Syndrome AKA Sicca syndrome
Triad of keratoconjunctivitis sicca, xerostomia, and thrumatoid arthritis.
RF is usually positive
Elevated C-reactive Protein, IgG, IgA, and IgM
80% has anti-Ro/SSA antibody.
>50% have anti-La/SSB antobodies
Only symptomatic treatment available.

71. Rheumatoid Nodules 20-30% of RA patients Subcutaneous nodules
Found anywhere on the body
Histologically shows dense foci of fibrinoid necrosis surrounded by histiocytes in palisaded arrangement.

73. Relapsing Polychondritis
Intermittent episodes of inflammation of the articular and nonarticular cartilage eventualing in chondrolysis.
MAGIC syndrome = Behcet’s + Relapsing Polychondritis (Mouth And Genital ulcers with Inflamed Cartilage)
Treatment with Dapsone for few weeks, then maintenance for 4-6 asymptomatic months.