Systemic sclerosis -fibrosis of skin and internal organs. The emergency: scleroderma renal crisis (SRC) -acute HTN + AKI + MAHA. Treatment: ACE inhibitors. Do NOT give steroids -they precipitate SRC.
C alcinosis ยท R aynaud's ยท E sophageal dysmotility ยท S clerodactyly ยท T elangiectasias
Scleroderma Renal Crisis (SRC)
SRC = acute hypertensive emergency + AKI + MAHA in a scleroderma patient. Occurs in ~10% of diffuse SSc, usually within the first 5 years. ACE inhibitors are life-saving. Steroids (especially > 15 mg prednisone/day) PRECIPITATE SRC.
Presentation: acute severe HTN (often > 180/120), rapid rise in Cr, oliguria, schistocytes on smear (MAHA), elevated LDH, thrombocytopenia (can mimic TTP)
Treatment:Captopril 6.25โ12.5 mg PO q8h, titrate aggressively to normalize BP. ACEi even if Cr is rising -do NOT hold for AKI. ACEi reduces mortality from > 80% to ~25%. Continue even if patient needs dialysis (some recover renal function months later).
ARBs are NOT a substitute -evidence is only for ACE inhibitors in SRC.
Prevention: avoid steroids > 15 mg prednisone/day in diffuse SSc. Monitor BP closely in all diffuse SSc patients.
๐ On Rounds
Why do steroids precipitate scleroderma renal crisis?
The mechanism isn't fully understood, but the leading theory is that steroids cause direct endothelial injury in the renal vasculature of scleroderma patients (whose vessels are already primed by intimal fibrosis and vascular obliteration). This triggers a cascade of renin release โ severe hypertension โ further endothelial damage โ MAHA โ AKI -a vicious cycle.
Why are ACE inhibitors life-saving in scleroderma renal crisis but ARBs are not?
This is a critical distinction. ACE inhibitors block the conversion of angiotensin I โ II, reducing both circulating and tissue-level angiotensin II. Before ACEi were used, scleroderma renal crisis had > 80% mortality at 1 year. With captopril, survival improved to ~60%. ARBs block the AT1 receptor but do NOT reduce angiotensin II levels -in fact, Ang II levels rise (compensatory).
What organ complications define limited vs diffuse scleroderma?
Prednisone > 15 mg/day is a risk factor for scleroderma renal crisis (SRC). The mechanism is not fully understood but likely involves steroid-induced endothelial injury in the renal vasculature โ activation of the renin-angiotensin system โ malignant hypertension + TMA + AKI. Anti-RNA polymerase III antibody patients are at highest risk. Rule: avoid steroids > 15 mg/day in diffuse scleroderma.
A scleroderma patient presents with sudden severe hypertension and AKI. What is this and how do you treat it?
Scleroderma renal crisis. Treat with ACE inhibitor (captopril) -titrate aggressively to normalize BP. This transformed survival from ~10% to ~65%. Do NOT use prophylactic ACEi -it may worsen outcomes. Start only when crisis occurs.
Which scleroderma antibody predicts ILD?
Anti-Scl-70 (anti-topoisomerase I) -associated with diffuse cutaneous SSc and interstitial lung disease. Anti-centromere = limited SSc (CREST) + pulmonary HTN. Anti-RNA polymerase III = renal crisis risk.
What is first-line treatment for SSc-ILD?
Mycophenolate mofetilScleroderma Lung Study II, 2016. Similar efficacy to cyclophosphamide with fewer side effects. Add nintedanibSENSCIS, 2019 if progressive despite MMF.
What screening should all scleroderma patients get annually?
PFTs with DLCO (ILD screening -FVC decline or isolated DLCO decline) and echocardiogram (PAH screening -RVSP, TR velocity). Isolated DLCO decline out of proportion to FVC suggests pulmonary hypertension rather than ILD.
๐ฃ Sample Presentation
One-Liner
"Mrs. Kim is a 48-year-old with diffuse cutaneous systemic sclerosis (on prednisone 20 mg for ILD) presenting with acute BP 210/130, Cr rising from 1.0 to 3.8 over 3 days, and schistocytes on peripheral smear. Scleroderma renal crisis."
Key Points to Cover on Rounds
Scleroderma renal crisis -hypertension + AKI + MAHA. Risk factor: prednisone >15 mg/day. Treatment: captopril 6.25 mg PO q8h, titrated aggressively to 25 mg TID over 24h (short-acting ACEi -captopril specifically, not ARB). DO NOT hold for rising Cr -it may take weeks to recover. Prednisone tapered urgently (precipitated the crisis). BP improved 210/130โ158/92 within 24h. Cr still rising (expected initially). Schistocytes โ monitoring for concurrent TMA. Nephrology following -dialysis if needed (may be temporary). Plan: continue aggressive ACEi titration, trend Cr/plt/LDH daily.
๐งช Workup
Workup
ANA -positive in > 90%. Nucleolar pattern suggestive of scleroderma.
Anti-Scl-70 (anti-topoisomerase I) -associated with diffuse cutaneous SSc + ILD. ~40% of dcSSc.
Anti-centromere -associated with limited cutaneous SSc (CREST) + pulmonary HTN. ~60% of lcSSc.
Anti-RNA polymerase III -associated with scleroderma renal crisis + rapidly progressive skin. Screen these patients carefully.
PFTs with DLCO -screen at baseline and q6-12 months. FVC decline or DLCO decline > 15% = progressive ILD. Isolated DLCO decline = pulmonary HTN.
HRCT chest -ILD pattern: NSIP most common (ground-glass opacities, subpleural sparing). UIP pattern less common.
Echocardiography -annual screening for pulmonary HTN (RVSP > 40, RV dilation). Confirm with right heart catheterization if suspected.
BMP + Cr -scleroderma renal crisis: sudden severe HTN + AKI + MAHA. Medical emergency. Treat with ACE inhibitor.
UA -proteinuria, hematuria in renal crisis
Modified Rodnan Skin Score (mRSS) -extent and severity of skin thickening. Track q6-12 months.
Nailfold capillaroscopy -dilated capillary loops, hemorrhages, avascular areas. Supports diagnosis + correlates with organ involvement.
โก Management
Management
Raynaud's: CCBs first-line (nifedipine 30-60 mg daily or amlodipine 5-10 mg). Severe/refractory: add PDE5 inhibitor (sildenafil), IV epoprostenol, or digital sympathectomy. Avoid beta-blockers.
Skin fibrosis (dcSSc): Methotrexate for early diffuse disease [van den Hoogen]. Mycophenolate for progressive skin thickening. Tocilizumab (IL-6 inhibitor) -emerging option [focuSSced, 2020]. For severe, rapidly progressive diffuse SSc: autologous stem cell transplant SCOT, Sullivan 2018
ILD (most common cause of death in SSc): Mycophenolate (first-line) SLS II, Tashkin 2016 or nintedanib SENSCIS, Distler 2019. Cyclophosphamide as alternative SLS I, Tashkin 2006. Screen with HRCT + PFTs (FVC trend). Refer for transplant if FVC < 50% or declining rapidly.
PAH: Right heart cath to confirm. Upfront combination: ambrisentan + tadalafil [AMBITION]. Add riociguat or selexipag for inadequate response. IV epoprostenol for FC III-IV.
Scleroderma renal crisis (SRC):ACE inhibitor immediately (captopril 6.25-12.5 mg q8h, titrate aggressively). Even if creatinine rising -continue ACEi. Do NOT use ARBs (no evidence). Avoid corticosteroids โฅ 15 mg prednisone (triggers SRC). Steen & Medsger, 1990
GI: GERD โ PPI (high-dose often needed). Gastroparesis โ prokinetics (metoclopramide, erythromycin). GAVE (watermelon stomach) โ APC ablation. Intestinal dysmotility โ rotating antibiotics for SIBO.
๐ Medications
Medications
Drug
Dose
Route
Notes
ILD (Interstitial Lung Disease)
Mycophenolate mofetil
2-3g daily
PO
First-line for SSc-ILD.Scleroderma Lung Study II, 2016 -similar efficacy to cyclophosphamide with fewer side effects.
Nintedanib
150 mg BID
PO
Antifibrotic. Add-on to MMF for progressive SSc-ILD SENSCIS, 2019. Slows FVC decline. GI side effects (diarrhea).
Tocilizumab
162 mg SQ weekly
SQ
Anti-IL-6. Preserves FVC in early dcSSc with elevated inflammatory markers [focuSSced, 2020].
Raynaud's
Nifedipine ER
30-90 mg daily
PO
First-line CCB for Raynaud's. Reduces frequency/severity of attacks.
Sildenafil
20 mg TID
PO
PDE5 inhibitor for severe Raynaud's + digital ulcers. Also used for PAH.
Iloprost
0.5-2 ng/kg/min ร 6h
IV
IV prostacyclin for refractory Raynaud's + digital ischemia.
Renal Crisis
ACE inhibitor (captopril)
6.25-25 mg TID, titrate aggressively
PO
Drug of choice for scleroderma renal crisis. Revolutionized survival from ~10% to ~65%. Do NOT use prophylactically -prophylactic ACEi may worsen outcomes. Start when crisis occurs.
Pulmonary Arterial Hypertension
Ambrisentan + tadalafil
10 mg + 40 mg daily
PO
Upfront combination ERA + PDE5i is standard AMBITION, 2015. Reduces hospitalization + clinical worsening.
HTN emergency + AKI + MAHA. Triggered by steroids > 15 mg/day. Treatment: CAPTOPRIL (short-acting ACEi) -titrate aggressively. Don't hold for rising Cr (may take weeks to recover).
๐ Screening
ILD: HRCT + PFTs at diagnosis, then annually. PAH: echo annually. GI: PPI for GERD. Raynaud: nifedipine/amlodipine. Avoid beta-blockers (worsen Raynaud).