Keywords

Bullous Pemphigoid

What Not To Miss

  • Drug induced

    • ◦ PEARL: PF ChaNGs—Penicillamine, PCN derivatives, PUVA, furosemide, captopril, NSAIDs, gold, sulfasalazine

  • Early Disease

    • ◦ Urticarial plaques or pruritus alone can be early manifestation, especially in the elderly

Key DDx

  • Diabetic bullae

  • Bullous impetigo

  • Bullous insect bite reaction

  • Epidermolysis Bullosa Acquisita

  • Pemphigus Vulgaris

  • Cicatricial pemphigoid

  • Allergic contact dermatitis

  • Bullous drug eruption

  • Porphyria cutanea tarda or pseudoporphyria

Work Up Pearls

  • Do two biopsies

    • ◦ One for H&E (lesional—edge of a blister)

    • ◦ Second for immunofluorescence (perilesional)

      • Ideally, a lesion less than 72 h old

      • PEARL: If only urticarial lesions, DIF should be lesional

  • Serum tests used if biopsy is inconclusive

    • ◦ 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

    • ◦ IIF for circulating anti-BMZ IgG

    • ◦ ELISA to detect Ab to BP180 and BP230

      • ELISA can also be used to monitor disease activity

Treatment Ladder

  • Mild-moderate disease

    • ◦ High potency topical steroids (Class I)

      • Can be used as monotherapy in severe disease [1]

    • ◦ Minocycline or doxycycline 100 mg twice daily [2] with or without niacinamide 0.5–2.0 g three times daily

  • Moderate-severe disease

    • ◦ Prednisone taper (slow), consider starting steroid sparing agent at or shortly after starting oral prednisone [3]

      • 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

      • Need lower doses in elderly and CKD patients [4]

    • ◦ Mycophenolate mofetil 1–3 g per day, divided twice daily [5]

    • ◦ Dapsone for mucosal-predominant or neutrophil/eosinophil-rich BP [6]: 50–200 mg daily

    • ◦ Azathioprine [5] titrate up to dose of 2.5 mg/kg daily

  • Severe or refractory disease

    • ◦ IVIG [7] 1–2 g/kg per cycle divided into 3–5 consecutive days per month for 3–6 months

    • ◦ Pulse solumedrol 2 gm IV total, divided over 3–5 days

    • ◦ Rituximab 1000 mg once and repeated in 2 weeks is 1 cycle [8, 9]

      • Patients often need more than 1 cycle

      • May need to continue second immunosuppressive until rituximab starts to work

      • Consider ordering CD20 lab after infusion to assess effect of medication

    • ◦ Omalizumab 150–300 mg every 4 weeks [10]

Dermatomyositis

What Not To Miss

  • Drug induced

    • ◦ Hydroxyurea (MC), statins, D-penicillamine, cyclophosphamide, BCG vaccine, TNF-α inhibitors

  • Occult malignancy

    • ◦ Up to 40% of adults may have an occult malignancy

    • ◦ Strong association with ovarian cancer in women

  • Amyopathic DM

    • ◦ Must do pulmonary and malignancy work up

  • DM associated with anti-MDA5 antibody

    • ◦ Can be fatal

    • ◦ Painful palmar papules, ulcerations in oral mucosa and overlying Gottron’s papules on elbows/knees

    • ◦ Rapidly progressive interstitial lung disease, panniculitis, arthritis, less muscle involvement [11]

      • ILD diagnosed with PFTs with DLCO (diffusing capacity of the lungs for carbon monoxide) and high resolution chest CT if needed

  • Children with DM can present with calcinosis cutis

Key DDx

  • Systemic lupus erythematosus

  • Mixed connective tissue disease

  • Phototoxic/photoallergic drug eruption

  • PMLE

  • Contact dermatitis

  • CTCL

Work Up Pearls [12,13,14]

  • Clinical findings

    • ◦ 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

    • ◦ Muscle disease: progressive symmetric proximal muscle weakness +/− esophageal muscles (dysphagia), cardiac disease (mostly subclinical EKG findings)

    • ◦ Other: pulmonary (15–65% with interstitial lung disease), arthralgia/arthritis

    • ◦ Remember DM can cause panniculitis and vasculitis in addition to the more common cutaneous manifestations

    • ◦ Also consider dermatomyositis in the differential of intractable scalp pruritus/dysesthesia

  • Labs

    • ◦ + ANA in 40%, CK, aldolase, CBC, CMP, TSH, UA

    • ◦ Antibodies to consider

      • Anti-Mi-2, anti-Jo-1, anti-SRP, anti-NXP-2, anti-PM-Scl, anti-Ku, anti-MDA5, anti-TIF-1-γ, anti-U1RNP

  • Diagnostics

    • ◦ PFTs with diffusing capacity of the lungs for carbon monoxide (DLCO), EMG, MRI or muscle biopsy , ECG, barium swallow (if esophageal symptoms).

    • ◦ Cancer screenings (age appropriate): CT chest/abdomen/pelvis, transvaginal/testicular ultrasound, colonoscopy, pap smear and mammogram.

  • Biopsy

    • ◦ PEARL: Can be identical to lupus erythematosus

Treatment Ladder

  • Skin-limited disease

    • ◦ 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

    • 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

      • Other: rituximab, cyclophosphamide, cyclosporine, leflunomide, chlorambucil, tacrolimus

      • If interstitial lung disease: steroids, rituximab, cyclophosphamide

  • Monitoring

    • ◦ Malignancy screens [13]

      • Most important within first 2 years, risk decreases 5 years after dx

    • ◦ Review of systems

Outside the Box Treatment Options

  • Tofacitinib for refractory patients

  • PEARL: TNF inhibitors are contraindicated as they can worsen myositis

Lupus Erythematosus

What Not To Miss

  • Active systemic involvement

    • ◦ Malar rash can be a sign so need at least CBC, CMP and UA

  • PEARL: Malar rash is persistent (vs. rosacea which waxes and wanes) and spares the nasolabial folds (vs. dermatomyositis and seborrhea, which involve NLF)

  • Drug induced

    • ◦ Procainamide, hydralazine, isoniazid, d-penicillamine, minocycline, TNF-α inhibitors

  • Rowell Syndrome [19]

    • ◦ EM-like lesions in a lupus patient

    • ◦ + 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

  • 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

    • ◦ Anti-dsDNA—nephritis, CNS

    • ◦ Anti-Smith—most specific for SLE

    • ◦ Ro and La—photosensitivity, Rowell’s, SCLE

    • ◦ Ro—counsel females of child bearing potential risk of neonatal lupus

      • If positive, refer to maternal-fetal-medicine or high-risk OB

  • Skin biopsy

  • Multidisciplinary evaluation based on lab abnormalities

    • ◦ Particularly rheumatology and nephrology

    • ◦ Cardiology and pulmonary as needed based on review of symptoms

Treatment Pearls [21]

  • Preventive interventions: smoking cessation, photoprotection

  • Mild disease

    • ◦ Hydroxychloroquine 5 mg/kg daily actual body weight (max 400 mg daily)

    • ◦ Chloroquine <2.3 mg/kg daily

    • ◦ Quinacrine 100 mg once daily

    • ◦ NSAIDs

    • ◦ Prednisone 5–15 mg daily for mild-moderate disease

  • Moderate-severe

    • ◦ Prednisone 1–2 mg/kg daily, can do IV pulse methylprednisolone 0.5–1.0 g daily for 3 days in acutely ill patients

    • ◦ Methotrexate 10–15 mg weekly

    • ◦ Azathioprine titrate up to dose of 2.5 mg/kg daily

  • Severe disease with major organ involvement

    • ◦ High dose prednisone + cyclophosphamide

    • ◦ Mycophenolate mofetil 1–3 g per day, divided into twice daily dosing

    • ◦ Azathioprine titrate up to dose of 2.5 mg/kg daily

  • Other

    • ◦ Thalidomide

      • PEARL: Thalidomide requires Thalomid REMS program

    • ◦ Lenalidomide

    • ◦ Dapsone

Out of the Box Treatment Options

  • Recalcitrant disease

    • ◦ Rituximab or belimumab

    • ◦ Abatacept

    • ◦ anti-IL-6 Ab

    • ◦ anti-IL-10 Ab

    • ◦ Ustekinumab

    • ◦ JAK inhibitors such as tofacitinib 5 mg twice daily

    • ◦ 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

  • Progression to SLE

    • ◦ Widespread (above and below the neck) and childhood DLE have higher rates of progression [22]

  • Squamous cell carcinomas

    • ◦ May form in chronic DLE scars

Key DDx

  • Scalp: tinea capitis, CCCA, lichen planopilaris

  • Face/body: seborrheic dermatitis , sarcoidosis, PMLE, granuloma faciale, Jessner’s, burn scar, syphilis

Diagnostic Pearls

  • Review of systems

  • Rare to see DLE below the neck if there is not involvement above the neck

  • ANA + in 5–25%

Treatment Ladder [23, 24]

  • Treat aggressively if active disease given risk for scarring

  • Camouflage cosmetics

  • Strict photoprotection

  • Topical

    • ◦ Topical or intralesional steroids

  • Systemic

    • ◦ Hydroxychloroquine 5 mg/kg daily up to 200 mg twice daily

    • ◦ Chloroquine < 2.3 mg/kg daily

    • ◦ +/− quinacrine 100 mg daily

  • Refractory disease

    • ◦ Methotrexate 10–20 mg weekly

    • ◦ Retinoids: acitretin 10–50 mg daily, isotretinoin 0.5–1.0 mg/kg daily

    • ◦ Systemic steroids (not recommended long term): 20–40 mg daily

    • ◦ Mycophenolate mofetil 1–3 g per day, divided into twice daily dosing

    • ◦ Dapsone 25–2’00 mg daily

Out Of The Box Treatment Options

  • Severe refractory disease: thalidomide, lenalidomide, IVIG

Subacute Cutaneous Lupus

What Not To Miss

  • Progression to SLE

    • ◦ Up to 30–50% can progress

    • ◦ Often is mild disease

  • Drug induced in up to 1/3 of cases [25]

    • ◦ Hydrochlorothiazide, terbinafine, griseofulvin, statins, NSAIDS, CCBs, antihistamines, PPIs, docetaxel, ACE-I, TNF-alpha inhibitors, many others

Key DDx

  • Erythema annulare centrifugum

  • Erythema multiforme

  • Annular psoriasis

  • Secondary syphilis

  • Tinea corporis

  • PMLE

Diagnostic Pearls [26]

  • Anti-Ro/SS-A (75–90%), Anti-La (30–40%), ANA (60–80%, usually speckled)

    • ◦ More common in Caucasians (vs. DLE)

Treatment Ladder [23, 24]

  • 1st line localized disease

    • ◦ Diligent photoprotection

    • ◦ Topical corticosteroid

    • ◦ Hydroxychloroquine 5 mg/kg daily up to 200 mg twice daily

  • 1st line severe disease

    • ◦ Topical corticosteroid

    • ◦ Hydroxychloroquine 5 mg/kg daily up to 200 mg twice daily + systemic corticosteroids

  • 2nd line—add

    • ◦ Quinacrine 100 mg daily

    • ◦ Methotrexate 10–25 mg weekly

    • ◦ Retinoids: acitretin 10–50 mg daily, isotretinoin 0.5–1.0 mg/kg daily

    • ◦ 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

    • ◦ Thiol/sulfa containing drugs, penicillamine, captopril, cephalosporins, gold, rifampin, indocin, penicillin, piroxicam, pyritinol, pyrazolone derivatives, enalapril, aspirin

  • ◦ Mucosal involvement

    • ◦ Ask about and examine ALL mucosal surface areas

    • ◦ Consider consultation with ophthalmology, dentistry/ENT, gynecology/urology

Key DDx

  • Paraneoplastic pemphigus

  • Pemphigus foliaceus

  • Bullous pemphigoid

  • Cicatricial pemphigoid

  • Erythema multiforme

  • Stevens-Johnson syndrome

  • Mycoplasma-induced rash and mucositis

    • ◦ PEARL: More common in young males

Diagnostic Pearls

  • ◦ Nikolsky sign and Asboe-Hansen sign

  • ◦ Biopsy

    • ◦ Lesional H&E

    • ◦ Perilesional DIF

  • ◦ Serum to support diagnosis and monitor disease activity

    • ◦ ELISA (Dsg 1 and 3)

    • ◦ IIF (monkey esophagus)

Treatment Ladder [28, 29]

  • First line

    • ◦ Systemic steroids + steroid sparing agent

    • ◦ 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

    • ◦ Azathioprine titrate up to dose of 2.5 mg/kg daily

    • ◦ Mycophenolate mofetil 2–3 g daily

  • Refractory disease

    • ◦ 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

    • ◦ Cardiovascular disease

    • ◦ Metabolic syndrome

    • ◦ NASH

    • ◦ Lymphoma

    • ◦ Mood disorders

    • ◦ May need multidisciplinary care

  • Erythrodermic or pustular psoriasis

    • ◦ Make sure to ask about any systemic steroids from PCP or Urgent Care

  • Psoriatic arthritis

    • ◦ Affects up to 30% of patients

    • ◦ Associated with morning stiffness, nail changes, tendon/ligament involvement

  • Concurrent or antecedent perianal or body fold cutaneous group A strep infection, especially in a child presenting with sudden onset guttate psoriasis

Key DDx

  • Atopic dermatitis

  • Contact dermatitis

  • Nummular dermatitis

  • Seborrheic dermatitis

  • 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

    • ◦ 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