Abstract
Autoimmune cutaneous conditions are an important part of medical dermatology . This chapter will cover the most common immunobullous diseases including bullous pemphigoid and pemphigus vulgaris, connective tissue diseases including dermatomyositis, lupus , morphea and systemic sclerosis, as well as psoriasis and pyoderma gangrenosum . The differential diagnosis, work-up pearls, ‘what not to miss’ and treatment ladder are included for a straightforward approach to common autoimmune cutaneous diseases.
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Keywords
Bullous Pemphigoid
What Not To Miss
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Drug induced
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◦ PEARL: PF ChaNGs—Penicillamine, PCN derivatives, PUVA, furosemide, captopril, NSAIDs, gold, sulfasalazine
-
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Early Disease
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◦ Urticarial plaques or pruritus alone can be early manifestation, especially in the elderly
-
Key DDx
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Diabetic bullae
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Bullous impetigo
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Bullous insect bite reaction
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Epidermolysis Bullosa Acquisita
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Pemphigus Vulgaris
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Cicatricial pemphigoid
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Allergic contact dermatitis
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Bullous drug eruption
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Porphyria cutanea tarda or pseudoporphyria
Work Up Pearls
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Do two biopsies
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◦ One for H&E (lesional—edge of a blister)
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◦ Second for immunofluorescence (perilesional)
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Ideally, a lesion less than 72 h old
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PEARL: If only urticarial lesions, DIF should be lesional
-
-
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Serum tests used if biopsy is inconclusive
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◦ Some areas, such as scalp, that may have extensive excoriation, may show nonspecific biopsy and negative DIF so IIF can be diagnostic in these cases
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◦ IIF for circulating anti-BMZ IgG
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◦ ELISA to detect Ab to BP180 and BP230
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ELISA can also be used to monitor disease activity
-
-
Treatment Ladder
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Mild-moderate disease
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Moderate-severe disease
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◦ Prednisone taper (slow), consider starting steroid sparing agent at or shortly after starting oral prednisone [3]
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0.5–1.0 mg/kg daily controls disease over 1–3 weeks, slowly taper once disease is controlled over 3 months
-
-
◦ Methotrexate 10–25 mg weekly
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Need lower doses in elderly and CKD patients [4]
-
-
◦ Mycophenolate mofetil 1–3 g per day, divided twice daily [5]
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◦ Dapsone for mucosal-predominant or neutrophil/eosinophil-rich BP [6]: 50–200 mg daily
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◦ Azathioprine [5] titrate up to dose of 2.5 mg/kg daily
-
-
Severe or refractory disease
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◦ IVIG [7] 1–2 g/kg per cycle divided into 3–5 consecutive days per month for 3–6 months
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◦ Pulse solumedrol 2 gm IV total, divided over 3–5 days
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◦ Rituximab 1000 mg once and repeated in 2 weeks is 1 cycle [8, 9]
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Patients often need more than 1 cycle
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May need to continue second immunosuppressive until rituximab starts to work
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Consider ordering CD20 lab after infusion to assess effect of medication
-
-
◦ Omalizumab 150–300 mg every 4 weeks [10]
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Dermatomyositis
What Not To Miss
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Drug induced
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◦ Hydroxyurea (MC), statins, D-penicillamine, cyclophosphamide, BCG vaccine, TNF-α inhibitors
-
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Occult malignancy
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◦ Up to 40% of adults may have an occult malignancy
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◦ Strong association with ovarian cancer in women
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Amyopathic DM
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◦ Must do pulmonary and malignancy work up
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DM associated with anti-MDA5 antibody
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◦ Can be fatal
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◦ Painful palmar papules, ulcerations in oral mucosa and overlying Gottron’s papules on elbows/knees
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◦ Rapidly progressive interstitial lung disease, panniculitis, arthritis, less muscle involvement [11]
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ILD diagnosed with PFTs with DLCO (diffusing capacity of the lungs for carbon monoxide) and high resolution chest CT if needed
-
-
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Children with DM can present with calcinosis cutis
Key DDx
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Systemic lupus erythematosus
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Mixed connective tissue disease
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Phototoxic/photoallergic drug eruption
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PMLE
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Contact dermatitis
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CTCL
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Clinical findings
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◦ Cutaneous findings: heliotrope rash, Gottron’s papules overlying joints of hands, photosensitivity, poikiloderma, shawl and V sign, holster sign, calcinosis cutis, mechanic’s hands, dilated capillary loops of nail folds, jagged cuticles, scalp erythema and scaling
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◦ Muscle disease: progressive symmetric proximal muscle weakness +/− esophageal muscles (dysphagia), cardiac disease (mostly subclinical EKG findings)
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◦ Other: pulmonary (15–65% with interstitial lung disease), arthralgia/arthritis
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◦ Remember DM can cause panniculitis and vasculitis in addition to the more common cutaneous manifestations
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◦ Also consider dermatomyositis in the differential of intractable scalp pruritus/dysesthesia
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Labs
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◦ + ANA in 40%, CK, aldolase, CBC, CMP, TSH, UA
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◦ Antibodies to consider
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Anti-Mi-2, anti-Jo-1, anti-SRP, anti-NXP-2, anti-PM-Scl, anti-Ku, anti-MDA5, anti-TIF-1-γ, anti-U1RNP
-
-
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Diagnostics
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◦ PFTs with diffusing capacity of the lungs for carbon monoxide (DLCO), EMG, MRI or muscle biopsy , ECG, barium swallow (if esophageal symptoms).
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◦ Cancer screenings (age appropriate): CT chest/abdomen/pelvis, transvaginal/testicular ultrasound, colonoscopy, pap smear and mammogram.
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Biopsy
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◦ PEARL: Can be identical to lupus erythematosus
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Treatment Ladder
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Skin-limited disease
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◦ 1st line (will not treat muscle disease): photoprotection , topical CS/CNI +/− hydroxychloroquine 5 mg/kg daily up to 200 mg twice daily; Caution: 30% of patients will get cutaneous drug eruption
-
◦ 2nd line: systemic steroids, methotrexate, mycophenolate mofetil, IVIG
-
-
Skin + muscle disease
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1st line:
-
systemic steroids [15] (slow taper) 0.5–1.0 mg/kg daily controls disease over 1–3 weeks, slowly taper once disease is controlled over 3 months
-
Methotrexate [16] 10–25 mg weekly
-
Mycophenolate mofetil 1.0–3.0 g daily, divided into twice daily dosing [15]
-
Azathioprine [17] titrate up to dose of 2.5 mg/kg daily
-
-
◦ 2nd line: IVIG [18] 1–2 g/kg per cycle divided into 3–5 consecutive days per month for 3–6 months
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Other: rituximab, cyclophosphamide, cyclosporine, leflunomide, chlorambucil, tacrolimus
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If interstitial lung disease: steroids, rituximab, cyclophosphamide
-
-
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Monitoring
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◦ Malignancy screens [13]
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Most important within first 2 years, risk decreases 5 years after dx
-
-
◦ Review of systems
-
Outside the Box Treatment Options
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Tofacitinib for refractory patients
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PEARL: TNF inhibitors are contraindicated as they can worsen myositis
Lupus Erythematosus
What Not To Miss
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Active systemic involvement
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◦ Malar rash can be a sign so need at least CBC, CMP and UA
-
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PEARL: Malar rash is persistent (vs. rosacea which waxes and wanes) and spares the nasolabial folds (vs. dermatomyositis and seborrhea, which involve NLF)
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Drug induced
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◦ Procainamide, hydralazine, isoniazid, d-penicillamine, minocycline, TNF-α inhibitors
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Rowell Syndrome [19]
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◦ EM-like lesions in a lupus patient
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◦ + ANA, Anti-Ro, RF
-
Work Up Pearls
2012 SLICC criteria: need 4, at least 1 clinical and 1 immunologic OR biopsy proven lupus nephritis and +ANA or dsDNA [20] | |
Dermatologic | ACLE, CCLE, non-scarring alopecia , oral/nasal ulcers |
Systemic | Synovitis, serositis, renal, neurologic |
Hematologic | Hemolytic anemia, leukopenia/lymphopenia, thrombocytopenia |
Immunologic | ANA, anti-dsDNA, anti-Sm, antiphospholipid, low complement (C3, C4 or CH50), direct Coombs’ test |
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Labs including CBC with diff, CMP, UA with microscopy, ANA, dsDNA, Ro/La, Sm, RNP, anti-phospholipid Abs (anticardiolipin, b2-glycoprotein, lupus anticoagulant ), C3/C4, CH50, ESR, CRP, +/− anti-histone (drug-induced), anti-U1RNP
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◦ Anti-dsDNA—nephritis, CNS
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◦ Anti-Smith—most specific for SLE
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◦ Ro and La—photosensitivity, Rowell’s, SCLE
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◦ Ro—counsel females of child bearing potential risk of neonatal lupus
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If positive, refer to maternal-fetal-medicine or high-risk OB
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Skin biopsy
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Multidisciplinary evaluation based on lab abnormalities
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◦ Particularly rheumatology and nephrology
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◦ Cardiology and pulmonary as needed based on review of symptoms
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Treatment Pearls [21]
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Preventive interventions: smoking cessation, photoprotection
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Mild disease
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◦ Hydroxychloroquine 5 mg/kg daily actual body weight (max 400 mg daily)
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◦ Chloroquine <2.3 mg/kg daily
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◦ Quinacrine 100 mg once daily
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◦ NSAIDs
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◦ Prednisone 5–15 mg daily for mild-moderate disease
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Moderate-severe
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◦ Prednisone 1–2 mg/kg daily, can do IV pulse methylprednisolone 0.5–1.0 g daily for 3 days in acutely ill patients
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◦ Methotrexate 10–15 mg weekly
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◦ Azathioprine titrate up to dose of 2.5 mg/kg daily
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Severe disease with major organ involvement
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◦ High dose prednisone + cyclophosphamide
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◦ Mycophenolate mofetil 1–3 g per day, divided into twice daily dosing
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◦ Azathioprine titrate up to dose of 2.5 mg/kg daily
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Other
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◦ Thalidomide
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PEARL: Thalidomide requires Thalomid REMS program
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◦ Lenalidomide
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◦ Dapsone
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Out of the Box Treatment Options
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Recalcitrant disease
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◦ Rituximab or belimumab
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◦ Abatacept
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◦ anti-IL-6 Ab
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◦ anti-IL-10 Ab
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◦ Ustekinumab
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◦ JAK inhibitors such as tofacitinib 5 mg twice daily
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◦ IVIG 1–2 g/kg per cycle divided into 3–5 consecutive days per month for 3–6 months
-
◦ Clinical trials
-
Discoid Lupus Erythematosus
What Not To Miss
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Progression to SLE
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◦ Widespread (above and below the neck) and childhood DLE have higher rates of progression [22]
-
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Squamous cell carcinomas
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◦ May form in chronic DLE scars
-
Key DDx
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Scalp: tinea capitis, CCCA, lichen planopilaris
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Face/body: seborrheic dermatitis , sarcoidosis, PMLE, granuloma faciale, Jessner’s, burn scar, syphilis
Diagnostic Pearls
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Review of systems
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Rare to see DLE below the neck if there is not involvement above the neck
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ANA + in 5–25%
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Treat aggressively if active disease given risk for scarring
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Camouflage cosmetics
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Strict photoprotection
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Topical
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◦ Topical or intralesional steroids
-
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Systemic
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◦ Hydroxychloroquine 5 mg/kg daily up to 200 mg twice daily
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◦ Chloroquine < 2.3 mg/kg daily
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◦ +/− quinacrine 100 mg daily
-
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Refractory disease
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◦ Methotrexate 10–20 mg weekly
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◦ Retinoids: acitretin 10–50 mg daily, isotretinoin 0.5–1.0 mg/kg daily
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◦ Systemic steroids (not recommended long term): 20–40 mg daily
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◦ Mycophenolate mofetil 1–3 g per day, divided into twice daily dosing
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◦ Dapsone 25–2’00 mg daily
-
Out Of The Box Treatment Options
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Severe refractory disease: thalidomide, lenalidomide, IVIG
Subacute Cutaneous Lupus
What Not To Miss
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Progression to SLE
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◦ Up to 30–50% can progress
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◦ Often is mild disease
-
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Drug induced in up to 1/3 of cases [25]
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◦ Hydrochlorothiazide, terbinafine, griseofulvin, statins, NSAIDS, CCBs, antihistamines, PPIs, docetaxel, ACE-I, TNF-alpha inhibitors, many others
-
Key DDx
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Erythema annulare centrifugum
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Erythema multiforme
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Annular psoriasis
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Secondary syphilis
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Tinea corporis
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PMLE
Diagnostic Pearls [26]
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Anti-Ro/SS-A (75–90%), Anti-La (30–40%), ANA (60–80%, usually speckled)
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◦ More common in Caucasians (vs. DLE)
-
-
1st line localized disease
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◦ Diligent photoprotection
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◦ Topical corticosteroid
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◦ Hydroxychloroquine 5 mg/kg daily up to 200 mg twice daily
-
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1st line severe disease
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◦ Topical corticosteroid
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◦ Hydroxychloroquine 5 mg/kg daily up to 200 mg twice daily + systemic corticosteroids
-
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2nd line—add
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◦ Quinacrine 100 mg daily
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◦ Methotrexate 10–25 mg weekly
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◦ Retinoids: acitretin 10–50 mg daily, isotretinoin 0.5–1.0 mg/kg daily
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◦ Dapsone 25–200 mg daily
-
◦ Mycophenolate mofetil 1–3 g per day, divided twice daily
-
Out Of The Box Treatment Options
-
Thalidomide for severe disease
Pemphigus Vulgaris
What Not To Miss [27]
-
◦ Drug induced
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◦ Thiol/sulfa containing drugs, penicillamine, captopril, cephalosporins, gold, rifampin, indocin, penicillin, piroxicam, pyritinol, pyrazolone derivatives, enalapril, aspirin
-
-
◦ Mucosal involvement
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◦ Ask about and examine ALL mucosal surface areas
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◦ Consider consultation with ophthalmology, dentistry/ENT, gynecology/urology
-
Key DDx
-
Paraneoplastic pemphigus
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Pemphigus foliaceus
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Bullous pemphigoid
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Cicatricial pemphigoid
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Erythema multiforme
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Stevens-Johnson syndrome
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Mycoplasma-induced rash and mucositis
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◦ PEARL: More common in young males
-
Diagnostic Pearls
-
◦ Nikolsky sign and Asboe-Hansen sign
-
◦ Biopsy
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◦ Lesional H&E
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◦ Perilesional DIF
-
-
◦ Serum to support diagnosis and monitor disease activity
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◦ ELISA (Dsg 1 and 3)
-
◦ IIF (monkey esophagus)
-
-
First line
-
◦ Systemic steroids + steroid sparing agent
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◦ Glucocorticoids 1.0–1.5 mg/kg daily
-
When no new lesions form, taper very slowly over months
-
-
◦ Rituximab 1000 mg once and repeated in 2 weeks is 1 cycle, repeat cycles every 6 months may be necessary
-
Emerging data supports this as first line with systemic steroids
-
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◦ Azathioprine titrate up to dose of 2.5 mg/kg daily
-
◦ Mycophenolate mofetil 2–3 g daily
-
-
Refractory disease
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◦ Methotrexate 10–25 mg weekly
-
◦ Dapsone 50–200 mg daily
-
◦ Cyclophosphamide 1–3 mg/kg daily
-
◦ Cyclosporine 2.5–5.0 mg/kg daily
-
◦ IVIG (may be combined with rituximab): 1–2 g/kg per cycle divided into 3–5 consecutive days per month for 3–6 months
-
Out Of The Box Treatment Options
-
Plasmapheresis or plasma exchange
-
Immunoadsorption
Psoriasis, Cutaneous
What Not To Miss
-
HIV infection
-
◦ Can precipitate or worsen existing psoriasis
-
-
Associated disorders
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◦ Cardiovascular disease
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◦ Metabolic syndrome
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◦ NASH
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◦ Lymphoma
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◦ Mood disorders
-
◦ May need multidisciplinary care
-
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Erythrodermic or pustular psoriasis
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◦ Make sure to ask about any systemic steroids from PCP or Urgent Care
-
-
Psoriatic arthritis
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◦ Affects up to 30% of patients
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◦ Associated with morning stiffness, nail changes, tendon/ligament involvement
-
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Concurrent or antecedent perianal or body fold cutaneous group A strep infection, especially in a child presenting with sudden onset guttate psoriasis
Key DDx
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Atopic dermatitis
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Contact dermatitis
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Nummular dermatitis
-
Seborrheic dermatitis
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Pityriasis rubra pilaris
-
Lichen planus
-
Subacute cutaneous lupus erythematosus
-
Mycosis fungoides
-
Tinea corporis
-
Crusted scabies
-
Secondary syphilis
-
Bowen’s —if few, smaller lesions
Work Up Pearls
-
Atypical appearing psoriasis can be psoriasiform drug eruption
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◦ Think of lithium, IFNs, B-blockers, ACE inhibitors, antimalarials, terbinafine, NSAIDs
-
-
Biopsy
-
Consider imaging for psoriatic arthritis
-
◦ May need rheumatology consultation to help evaluate
-
Treatment Ladder: Cutaneous [30, 31]
-
Topicals: for mild (as monotherapy) to severe disease
-
◦ Topical corticosteroids
-
◦ Calcipotriene
-
◦ Coal tar
-
◦ Anthralin
-
◦ Calcineurin inhibitors
-
◦ Calcitriol
-
◦ Tazarotene or salicylic acid for hyperkeratotic lesions
-
◦ Intralesional triamcinolone for treatment resistant plaques
-
-
Phototherapy [32]
-
◦ NBUVB two to three times weekly
-
◦ Excimer laser (localized lesions)
-
◦ PUVA is 2nd line
-
-
Systemic
-
◦ Methotrexate 10–25 mg weekly
-
◦ Acitretin (erythrodermic, pustular) 25 mg every other day to 50 mg daily
-
◦ Cyclosporine 3–5 mg/kg daily
-
◦ Apremilast 30 mg twice daily (after starter pack)
-
-
Biologics [33]: all given subcutaneously except infliximab which is given intravenously*
-
◦ TNF-a inhibitors:
-
PEARL: Avoid in patients with CHF or multiple sclerosis
-
Adalimumab: 80 mg initial dose, followed by 40 mg one week later then every other week
-
Etanercept: 50 mg twice weekly for the initial 3 months, then 50 mg weekly
-
Infliximab: 5 mg/kg given at weeks 0, 2, 6, then every 8 weeks thereafter *
-
Certolizumab: 400 mg at weeks 0, 2 and 4, followed by 200 mg every other week
-
-
◦ IL-12/23 inhibitor:
-
Ustekinumab: 45 mg at weeks 0, 4, and every 12 weeks thereafter; 90 mg for patients >100 kg (dosing is good for compliance concerns)
-
-
◦ IL-23 inhibitors:
-
Guselkumab:100 mg at weeks 0, 4, and then every 8 weeks
-
Tildrakizumab: 100 mg at weeks 0, 4, and then every 12 weeks
-
-
◦ IL-17 inhibitors:
-
PEARL: Avoid in patients with IBD. Look for mucocutaneous candidiasis
-
Secukinumab: 300 mg at weeks 0, 1, 2, 3, and 4 then every 4 weeks
-
Ixekizumab: 160 mg at week 0, followed by 80 mg at weeks 2, 4, 6, 8, 10, 12 and then every 4 weeks
-
Brodalumab: 210 mg at weeks 0, 1, 2 and then every 2 weeks
-
PEARL: requires participation in a Risk Evaluation and Mitigation Strategy program due to concerns for suicidality.
-
-
-
-
Other
-
◦ Consider “day hospital” (steroid wraps and phototherapy ) for severe disease—can be done in a clinic setting or with wraps alone at home
-
Treatment Ladder: Scalp [34]
-
Topicals
-
◦ 3 or 5% salicylic acid compounded with fluocinonide cream or ointment
-
◦ Clobetasol or betamethasone dipropionate-calcipotriene foam/solution
-
◦ Tar or salicylic based shampoos
-
◦ Intralesional triamcinolone for localized thick plaques
-
-
Excimer laser
-
◦ PEARL: NB-UVB will not reach the scalp through hair
-
-
Systemics as in cutaneous psoriasis section
-
◦ Particularly apremilast and biologics
-
Treatment ladder, Nails [35]
-
Gentle hand/foot care
-
◦ Avoid trauma (manicures)
-
◦ Apply emollients regularly
-
◦ Keep nails trimmed
-
-
High potency topical steroid under occlusion +/− vitamin D ointment to nail plate, hyponychium, proximal/lateral nail folds
-
2nd line: tazarotene or topical calcineurin inhibitors
-
1% 5FU solution or 5% 5FU cream without occlusion BID for 6 months
-
Intralesional triamcinolone 2.5 mg/ml into proximal nail fold/matrix
-
Systemic
-
◦ Biologics
-
◦ Acitretin
-
◦ Apremilast
-
◦ Methotrexate
-
Out Of The Box Treatment Options
-
Tofacitinib 5 mg BID
-
IVIG 1–2 g/kg per cycle divided into 3–5 consecutive days per month for 3–6 months
In The Context Of…
-
Erythroderma
-
◦ Cyclosporine usually has fastest onset of action
-
◦ If erythroderma and impaired kidney function, consider guselkumab, which may be faster acting [36]
-
-
Co-morbid metabolic syndrome
-
◦ Consider metformin
-
-
Pregnancy
-
◦ Topical steroids
-
◦ NBUVB
-
◦ Biologics (anti-TNFs, IL17, IL23) are mostly category B
-
Discuss if risks outweigh benefits, consider enrolling in pregnancy registry
-
Try to stop anti-TNFs at 30 weeks gestation and postpone live vaccinations in newborn babies
-
Certolizumab showed low transfer of the drug through placenta and minimal mother-to-infant transfer from breast milk in pharmacokinetic data.
-
-
◦ Cyclosporine (Category C) for severe disease
-
◦ PEARL: Impetigo herpetiformis is treated with systemic corticosteroids
Pyoderma Gangrenosum
What Not To Miss
-
Unusual sites
-
◦ Rarely PG can involve the eyes, lungs, heart, liver, gastrointestinal tract, CNS and lymphatics
-
-
Other PG variations
-
◦ Pustular, bullous, vegetative and suppurative panniculitis
-
-
PEARL: Avoid unnecessary elective surgical procedures and debridement—if absolutely necessary, perform while on immunosuppressive therapy.
Key DDx
-
Infection
-
◦ PG is a diagnosis of exclusion and infection must be ruled out with tissue culture
-
-
Consider underlying genetic causes including PAPA, PASH and PAPASH syndromes
Work Up Pearls [37]
-
Biopsy at edge of ulcer for H&E + tissue culture to rule out infection
-
Work-up (search for underlying disease)—CBC, ESR, LFTs, BUN/Cr, ANA, SPEP (IgA gammopathy), UA, hepatitis panel, ANCAs, RF, anti-phospholipid antibodies; +/− CXR, colonoscopy
Treatment Ladder [38]
-
Local wound care with non-adherent dressing, avoiding pathergy, pain management (important to keep it moist)
-
Topical
-
◦ Intralesional triamcinolone 10–20 mg/ml
-
◦ Topical corticosteroids/calcineurin inhibitors to periphery of ulcer and antimicrobial (i/e metronidazole gel) to the center of the ulcer
-
-
Antibiotics
-
◦ Doxycycline 100 mg twice daily
-
◦ Minocycline 100 mg twice daily
-
◦ Dapsone 50–200 mg daily
-
-
Systemic
-
◦ Glucocorticoid starting dose at 1 mg/kg
-
◦ Cyclosporine 4–5 mg/kg daily and taper as tolerated
-
◦ Azathioprine titrate up to dose of 2.5 mg/kg daily
-
◦ Methotrexate 10–30 mg per week
-
◦ Mycophenolate mofetil 2–3 g per day, divided twice daily
-
◦ IVIG 1–2 g/kg per cycle divided into 3–5 consecutive days per month for 3–6 months
-
-
Biologics : TNF-a inhibitors
Outside the Box Treatment Options
-
Thalidomide
-
Sulfasalazine
-
Clofazimine
-
Anakinra
-
Canakinumab
Morphea
What Not To Miss
-
Genital lichen sclerosus et atrophicus
-
◦ Can occur in patients with plaque-type morphea
-
-
Limb contractures or limb-length discrepancies
-
◦ This can result from linear morphea
-
-
Linear morphea of the head (En coup de sabre and Parry-Romberg syndrome) can result in alopecia , ocular, neurologic and dental abnormalities
-
◦ Both must be treated aggressively
-
Key DDx
-
Systemic sclerosis
-
Nephrogenic fibrosing dermopathy
-
Eosinophilic fasciitis
-
Lipodermatosclerosis
-
Drug or chemical induced sclerodermoid reaction (PEARL: Think taxanes or PVC)
Work Up Pearls
-
Skin biopsy is confirmatory
-
◦ PEARL: Biopsy containing fascia and muscle is needed if eosinophilic fasciitis is on the differential
-
-
X-rays for linear morphea
-
◦ MRI can evaluate for deeper involvement
-
-
Testing for auto-Abs only indicated if signs of another autoimmune disease [39]
Treatment Ladder [40]
-
Circumscribed lesions
-
◦ Topical or intralesional corticosteroids
-
◦ Topical calcineurin inhibitor
-
◦ Topical calcipotriene
-
◦ Topical imiquimod
-
◦ UVA 1 or NBUVB (if UVA not available)
-
PEARL: UVA -1 preferred because it penetrates deeper
-
-
-
Generalized or localized with functional/cosmetic threat (face, over joints)
-
◦ Methotrexate 15–25 mg weekly +/− systemic prednisone 1 mg/kg daily for 2–3 months
-
◦ Mycophenolate mofetil 2–3 g daily, divided twice daily
-
-
Consultation with PT/OT, Orthopedics/Plastic surgery/OMSF
-
Other options
-
◦ Cyclosporine 2–5 mg/kg daily in 2 divided doses
-
◦ Hydroxychloroquine 5 mg/kg daily up to 200 mg twice daily
-
◦ Acitretin 12.5–50 mg daily + PUVA
-
◦ Extracorporeal photopheresis
-
◦ Bosentan 31.25–62.5 mg twice daily
-
Outside Of The Box Treatment Options
-
Fillers for improved cosmesis once morphea stabilizes
-
CO2 laser to decrease contractures and increase mobility over joints
-
Infliximab, rituximab, imatinib, JAK inhibitors, thalidomide
Systemic Sclerosis
What Not To Miss
-
PEARL: African American patients have a more severe course and increased mortality
-
Extracutaneous findings
-
◦ Pulmonary disease is the leading cause of mortality.
-
◦ GI is the most common site of visceral disease and associated with increased morbidity but not mortality
-
◦ Scleroderma renal crisis risk can be decreased with ACE-I
-
◦ Scleroderma renal crisis has been associated with use of systemic corticosteroids in retrospective studies
-
Key DDx
-
Generalized morphea
-
Scleredema
-
Scleromyxedema
-
Eosinophilic fasciitis
-
Nephrogenic systemic fibrosis
-
Chronic GVHD
-
Exogeneous: polyvinyl chloride (PVC) exposure, bleomycin toxicity, radiation effects
Workup Pearls
-
CBC with diff, BUN, Cr, CK, U/A,
-
Auto-antibodies
-
◦ ANA (95% +), anti-Scl-70
-
◦ anti-centromere Ab (associated with CREST)
-
◦ anti-RNA pol III Ab (associated with rapidly progressive skin involvement, renal disease and cancer)
-
-
At time of diagnosis and for monitoring: high resolution CT of lungs, PFTs with DLCO, ECG, ECHO (to assess pulmonary arterial HTN), GI consultation as appropriate
-
Diagnosis [41]
ACR/EULAR 2013 Criteria. ≥ 9 = definite SSc. | |
---|---|
Cutaneous findings: | Systemic findings: |
Skin thickening of fingers proximal to MCP joint (9) | Pulm art. HTN (2) or ILD (2) |
Skin thickening of the fingers: puffy fingers (2) or sclerodactyly (4) | Raynaud’s phenomenon (3) |
Fingertip lesions: ulcers (2), pitting scars (3) | Ab’s (ANA, anti-Scl-70, anti-RNA pol III) (3 max) |
Telangiectasia (2) | |
Abnormal nail fold capillaries (2) |
Treatment Ladder (cutaneous) [42]
-
Multidisciplinary approach
-
◦ Rheumatology +/− nephrology, pulmonology, gastroenterology
-
-
1st line
-
◦ Oral corticosteroids
-
◦ Methotrexate 10–25 mg weekly
-
◦ Mycophenolate mofetil 2–3 g per day, divided twice daily
-
◦ PUVA or UVA 1
-
◦ Rituximab 1000 mg once and repeated in 2 weeks is 1 cycle, repeat cycles may be necessary
-
-
2nd line
-
◦ Azathioprine titrate up to dose of 2.5 mg/kg daily
-
◦ Cyclophosphamide 1–3 mg/kg daily
-
◦ IVIG 1–2 g/kg per cycle divided into 3–5 consecutive days per month for 3–6 months
-
◦ Bosentan
-
◦ Sildenafil
-
Outside Of The Box Treatment Options
-
Myeloablative autologous hematopoietic stem-cell transplantation
-
Low-energy extracorporeal shock-wave therapy
-
Clinical trials for refractory or progressive disease
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Mancuso, J.B., Rambhatla, P.V. (2020). Immune-mediated Disorders. In: Lim, H., Kohen, L., Schneider, S., Yeager, D. (eds) Practical Guide to Dermatology. Springer, Cham. https://doi.org/10.1007/978-3-030-18015-7_1
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