Rheumatology: Emergencies, pregnancy and other systemic diseases

• Emergencies: Rheumatological Emergencies — Overview | Infection in the Immunosuppressed Patient | Pulmonary–Renal Syndrome and Renal Crises | Lupus and APS Emergencies | Macrophage Activation Syndrome | Drug-related Emergencies | Spinal Emergencies in Rheumatic Disease | Severe Myositis and Digital Ischaemia | Immune Checkpoint Inhibitor Toxicity
• Pregnancy: Pregnancy and Rheumatic Disease | Drugs in Pregnancy and Breastfeeding
• Other systemic diseases: Adult-onset Still's Disease | Sarcoidosis and Erythema Nodosum | IgG4-related Disease and Relapsing Polychondritis | Autoinflammatory Syndromes and Amyloidosis
• Revision: Emergencies and Systemic Diseases at a Glance | Spot the Diagnosis | Exam-style Scenarios | Key Points | Guidelines and Further Reading

🩺 Rheumatological emergencies, pregnancy and other systemic diseases — page 6 (the last) of the Rheumatology chapter. Rheumatology emergencies come from three directions: the disease itself (vasculitis, lupus, renal crisis, MAS), its treatment (infection, drug toxicity, adrenal crisis) and structural damage (unstable spines). This page also covers pregnancy, which needs planning in every woman of childbearing age with rheumatic disease, and a group of rarer systemic diseases that often appear as "fever of unknown origin" or "unusual rash and joint pains".
Your four questions for every patient: Is this a disease flare, an infection, or a drug effect — or more than one? Which organ is failing, and who needs to know now? Is the patient on steroids, DMARDs or biologics that change how illness presents and how it must be treated? For women of childbearing age — what is the contraception and pregnancy plan?

Rheumatological Emergencies — Overview

Infection in the Immunosuppressed Patient

• Infection is the commonest serious complication of rheumatic disease treatment — and presentations are often blunted (little fever, normal-looking joint, low CRP with tocilizumab).
• Higher-risk situations — high-dose steroids (over 20 mg prednisolone), combination immunosuppression, rituximab (low immunoglobulins), cyclophosphamide, older age, diabetes, lung disease, recent surgery.
• Organisms to think about:
  • Common bacteria — pneumonia, cellulitis, UTI, septic arthritis.
  • Opportunistic — Pneumocystis jirovecii (PJP — breathlessness, hypoxia on exercise, bilateral infiltrates; prevent with co-trimoxazole), TB (often extrapulmonary on anti-TNF), Listeria, Legionella, fungi.
  • Viral — shingles (JAK inhibitors, steroids), hepatitis B reactivation (rituximab), CMV, PML (JC virus — rituximab).
• Management:
  • Assess and treat sepsis promptly — low threshold for blood cultures and antibiotics.
  • Pause DMARDs and biologics during significant infection (restart when recovered).
  • Don't stop long-term steroids — increase them (sick day rules; IV hydrocortisone if very unwell or vomiting) to prevent adrenal crisis.
  • Avoid trimethoprim and co-trimoxazole treatment doses with methotrexate (prophylactic co-trimoxazole is used with care under specialist supervision).
• Prevention — vaccination, PJP prophylaxis where indicated, TB and hepatitis screening before biologics, steroid minimisation.

Pulmonary–Renal Syndrome and Renal Crises

• Pulmonary–renal syndrome — diffuse alveolar haemorrhage plus rapidly progressive glomerulonephritis:
  • Causes — ANCA vasculitis (commonest), anti-GBM disease, SLE, cryoglobulinaemia, IgA vasculitis.
  • Signs of alveolar haemorrhage — haemoptysis (may be absent), hypoxia, falling Hb, new bilateral infiltrates, raised TLCO.
  • Kidneys — haematuria with red cell casts, proteinuria, rising creatinine over days.
  • Action — ICU and renal input; urgent ANCA and anti-GBM; exclude infection; IV methylprednisolone; plasma exchange (anti-GBM; consider in ANCA with severe haemorrhage or kidney failure); rituximab or cyclophosphamide (see page 5).
• Scleroderma renal crisis — early diffuse systemic sclerosis (anti-RNA polymerase III), often after high-dose steroids: accelerated hypertension, AKI, MAHA, pulmonary oedema, headache, seizures. ACE inhibitor (captopril) titrated quickly, continue even if creatinine rises; avoid IV nitrates and over-rapid BP falls; dialysis (recovery possible over 1–2 years). See page 4.
• Thrombotic microangiopathy in SLE or APS — MAHA, low platelets, AKI — consider TTP (ADAMTS13), catastrophic APS; plasma exchange.

Lupus and APS Emergencies

• Severe lupus flare — first decide flare or infection (CRP high in infection; low C3/C4 and rising anti-dsDNA in flare) — often treat both until clear.
• Lupus nephritis with rising creatinine — urgent renal referral, biopsy, IV methylprednisolone plus mycophenolate or cyclophosphamide.
• Neuropsychiatric lupus — seizures, psychosis, confusion, stroke, transverse myelitis:
  • Exclude infection (meningitis — LP), metabolic causes, drugs (steroid psychosis), hypertension (PRES), antiphospholipid-related stroke (anticoagulate), cerebral venous sinus thrombosis.
  • MRI brain, CSF, EEG; IV methylprednisolone plus cyclophosphamide for inflammatory disease.
• Severe cytopenias — autoimmune haemolytic anaemia, thrombocytopenia (platelets under 20) — steroids, IVIG, rituximab.
• Serositis — large pericardial effusion and tamponade (rare); myocarditis (troponin, echo, MRI).
• Catastrophic APS — thrombosis in 3 or more organs within a week (kidneys, lungs, brain, skin, adrenals — adrenal crisis), often triggered by infection, surgery or stopping anticoagulation; triple therapy — therapeutic heparin + high-dose steroids + plasma exchange and/or IVIG; rituximab or eculizumab in refractory cases; ICU; mortality about 30–40%.

Macrophage Activation Syndrome

• Macrophage activation syndrome (MAS) — a form of secondary haemophagocytic lymphohistiocytosis (HLH) — uncontrolled immune activation and a "cytokine storm" in rheumatic disease (especially adult-onset Still's disease, systemic JIA and SLE), often triggered by infection (EBV, CMV) or drug changes. Other causes of HLH — lymphoma, infections, immunotherapy.
• Features:
  • Persistent high fever.
  • Cytopenias (falling platelets and white cells — note a falling platelet count in a patient with Still's is a warning sign).
  • Very high ferritin (often over 10,000).
  • Raised triglycerides, low fibrinogen, raised LFTs and LDH, falling ESR (fibrinogen consumption) with high CRP.
  • Hepatosplenomegaly, lymphadenopathy, rash, confusion, DIC, multi-organ failure.
• Diagnosis — clinical and lab criteria (HScore, HLH-2004); bone marrow may show haemophagocytosis (not required).
• Treatment — emergency with specialist (haematology and rheumatology) input: high-dose IV methylprednisolone, anakinra (IL-1 blockade — often first-line in rheumatic MAS), ciclosporin, IVIG; etoposide in refractory or malignant HLH; treat triggers (infection); ICU support.

Drug-related Emergencies

• Methotrexate toxicity:
  • Causes — daily instead of weekly dosing, trimethoprim or co-trimoxazole, AKI or dehydration, NSAIDs, overdose.
  • Features — mouth ulcers, diarrhoea, pancytopenia, neutropenic sepsis, liver injury, kidney injury.
  • Treatment — stop methotrexate, folinic acid (calcium folinate) rescue, treat sepsis, IV fluids, haematology advice; glucarpidase for very high levels with kidney failure (specialist).
• Methotrexate pneumonitis — new dry cough, breathlessness, fever, hypoxia (usually in the first year) — stop methotrexate, exclude infection (PJP), high-dose steroids; don't restart.
• Drug-induced neutropenia (any DMARD, biologics) — neutrophils under 1.0 with fever — neutropenic sepsis pathway (antibiotics within 1 hour).
• Adrenal crisis — steroid users who stop suddenly, miss doses or become ill (vomiting, diarrhoea, surgery): hypotension, vomiting, abdominal pain, confusion, low sodium, high potassium, low glucose — IV or IM hydrocortisone 100 mg immediately, then 200 mg/24 hours (infusion or 50 mg 6-hourly), IV fluids (see the Adrenal Disease chapter).
• Severe drug reactions — SJS/TEN and DRESS (allopurinol, sulfasalazine, NSAIDs) — stop the drug, dermatology and ICU/burns care.
• Infusion reactions — rituximab and infliximab (fever, rigors, hypotension, bronchospasm) — stop or slow the infusion, antihistamine, hydrocortisone, adrenaline if anaphylaxis.
• Hydroxychloroquine overdose — very dangerous (QT prolongation, arrhythmias, hypokalaemia) — TOXBASE advice.
• Colchicine overdose — vomiting and diarrhoea, then multi-organ failure and marrow failure — supportive care, TOXBASE.
• Bisphosphonates and denosumab — atypical femoral fractures (thigh pain), jaw osteonecrosis, rebound vertebral fractures after stopping denosumab (see the Bone Medicine chapter).

Spinal Emergencies in Rheumatic Disease

• Atlanto-axial subluxation in RA:
  • Erosion of the odontoid and the transverse ligament lets C1 slip forward on C2.
  • Neck pain radiating to the occiput, tingling hands, clumsy hands, gait problems, Lhermitte's sign, upper motor neurone signs; can cause sudden death.
  • Risk — long-standing, erosive RA; danger during intubation (neck flexion) and after falls.
  • Investigation — flexion–extension X-rays, MRI (cord compression).
  • Management — neck collar, urgent spinal surgery referral (fusion) if myelopathy.
• Spinal fractures in ankylosing spondylitis and DISH:
  • A fused, brittle spine (like a long bone) can fracture after minor trauma — often unstable, with a high risk of cord injury.
  • New neck or back pain after any fall — immobilise in the patient's usual (often flexed) posture; CT of the whole spine (± MRI) — X-rays often miss them.
• Cauda equina syndrome — rare complication of long-standing AS (dural ectasia).
• Spinal infection (discitis, epidural abscess) — back pain and fever in immunosuppressed patients — urgent MRI.
• Osteoporotic vertebral fractures — steroid users; sudden back pain, height loss.
• Metastatic spinal cord compression — see the Oncological Emergencies chapter.

Severe Myositis and Digital Ischaemia

• Severe myositis — rapidly worsening weakness with:
  • Dysphagia and aspiration (pharyngeal weakness) — speech and language assessment, NG feeding.
  • Respiratory muscle weakness — monitor FVC (not just SpO₂), ICU if falling.
  • Rapidly progressive ILD (especially anti-MDA5) — can be fatal within weeks — aggressive combination immunosuppression.
  • Myocarditis — troponin, ECG, cardiac MRI.
  • Rhabdomyolysis — very high CK, dark urine, AKI.
• Treatment — IV methylprednisolone, IVIG, early steroid-sparing drugs, rituximab or cyclophosphamide.
• Critical digital ischaemia — persistent pallor or cyanosis of a finger, severe pain, necrosis:
  • Causes — systemic sclerosis, vasculitis, emboli (AF, subclavian aneurysm), APS, cryoglobulinaemia, drugs (vasopressors, cocaine), arterial injection.
  • Admit — warm environment, analgesia, IV iloprost, antiplatelet ± anticoagulation (if clot), treat infection, stop vasoconstrictors; look for large-vessel causes (vascular imaging).

Immune Checkpoint Inhibitor Toxicity

• Immune checkpoint inhibitors (anti-PD-1 — pembrolizumab, nivolumab; anti-PD-L1; anti-CTLA-4 — ipilimumab) used in cancer can cause immune-related adverse events (irAEs) in any organ.
• Rheumatic irAEs — inflammatory arthritis (RA-like or PMR-like), myositis (may occur with myocarditis and myasthenia gravis — a dangerous "overlap" — check CK, troponin and respiratory function), sicca syndrome, vasculitis.
• Management — liaise with oncology; grade the toxicity; NSAIDs and low-dose steroids for mild arthritis; higher-dose steroids, DMARDs or biologics (IL-6 or TNF inhibitors) for severe disease; checkpoint inhibitor may need to be paused or stopped.
• Myocarditis–myositis–myasthenia overlap — an emergency — high-dose IV methylprednisolone, ICU, specialist advice.
• Other irAEs — colitis, hepatitis, pneumonitis, thyroiditis, hypophysitis (adrenal insufficiency), type 1 diabetes (see the Oncology chapters).

Pregnancy and Rheumatic Disease

• Plan ahead — discuss contraception and pregnancy plans with every woman of childbearing age; aim for at least 6 months of stable, quiet disease before conception on pregnancy-compatible drugs.
• Disease course in pregnancy:
  • RA — often improves in pregnancy, with flares after delivery.
  • SLE — may flare in pregnancy and post-partum; lupus nephritis flare versus pre-eclampsia can be hard to tell apart (both cause hypertension and proteinuria; low complement and active urine sediment favour lupus; sFlt-1/PlGF ratio favours pre-eclampsia).
  • Axial SpA — usually unchanged.
  • Systemic sclerosis — risk of renal crisis; avoid pregnancy in early diffuse disease or with PAH.
• High-risk situations — pulmonary arterial hypertension (pregnancy is high risk — advise against), severe ILD, active lupus nephritis, previous severe pre-eclampsia, kidney impairment, recent stroke.
• Antibody-related risks:
  • Anti-Ro/La — congenital heart block (about 2%; about 15–20% if a previous affected child) — weekly or fortnightly fetal heart rate monitoring from 16 to 26 weeks; hydroxychloroquine reduces the risk.
  • Antiphospholipid antibodies — miscarriage, pre-eclampsia, growth restriction, stillbirth, thrombosis — aspirin plus LMWH (see page 4).
• All women with SLE or APS — low-dose aspirin from 12 weeks (pre-eclampsia prevention, NICE NG133) and joint care with obstetric medicine.
• Post-partum — VTE prophylaxis, plan for flares, check drug compatibility with breastfeeding.
• Contraception — avoid oestrogen-containing contraception with antiphospholipid antibodies, active SLE, or high VTE risk; progestogen-only methods and copper or levonorgestrel IUDs are generally safe.
• Fertility — cyclophosphamide can cause ovarian failure (GnRH analogue protection, egg or embryo freezing); sulfasalazine reduces sperm count (reversible).

Drugs in Pregnancy and Breastfeeding

• Men — methotrexate, sulfasalazine (lowers sperm count), azathioprine and anti-TNF can usually be continued when trying to conceive (BSR 2022); cyclophosphamide and leflunomide need specialist advice.
• Babies exposed to biologics in late pregnancy — no live vaccines (rotavirus, BCG) until about 6 months (seek specialist advice for each drug).

Adult-onset Still's Disease

• Rare autoinflammatory disease of young adults (16–35), a cause of fever of unknown origin.
• Features:
  • Daily (quotidian) spiking fevers, often in the evening, over 39°C, returning to normal between spikes.
  • Evanescent salmon-pink rash appearing with the fever (trunk and limbs) — may be triggered by scratching (Koebner phenomenon).
  • Arthralgia or arthritis (knees, wrists, ankles).
  • Sore throat, lymphadenopathy, hepatosplenomegaly, serositis.
• Blood tests — very high ferritin (often over 3,000; low glycosylated ferritin), neutrophil leucocytosis, high CRP and ESR, abnormal LFTs; ANA and RF negative.
• Diagnosis of exclusion (Yamaguchi criteria) — rule out infection (endocarditis, EBV, CMV, HIV, TB), lymphoma and other cancers, vasculitis.
• Treatment — NSAIDs (mild), steroids, methotrexate; IL-1 inhibitors (anakinra, canakinumab) or IL-6 (tocilizumab) for steroid-dependent or refractory disease.
• Complication — macrophage activation syndrome (falling platelets, falling ESR, rising ferritin and triglycerides).

Sarcoidosis and Erythema Nodosum

• Sarcoidosis — multi-system non-caseating granulomas (lungs, lymph nodes, skin, eyes, heart, nerves) — see the Respiratory chapters.
• Musculoskeletal sarcoid:
  • Löfgren's syndrome — acute erythema nodosum, bilateral hilar lymphadenopathy, ankle periarthritis (swollen, painful ankles) ± fever — good prognosis (usually resolves within 2 years); NSAIDs, short steroid course.
  • Chronic sarcoid arthritis, dactylitis with lytic bone lesions ("lace-like"), myopathy.
  • Hypercalcaemia (granulomas make active vitamin D) — avoid vitamin D supplements.
  • Cardiac sarcoid (heart block, VT, sudden death) and neurosarcoid — serious.
• Investigations — chest X-ray or CT, serum ACE (not specific), calcium and urine calcium, biopsy (lymph node — EBUS, skin), ECG, eye examination.
• Erythema nodosum — tender red-purple nodules on the shins (inflamed fat — panniculitis); settles over weeks with bruise-like colour change. Causes:
  • Infections — streptococcal throat infection (commonest), TB, Yersinia, Mycoplasma, EBV.
  • Sarcoidosis, IBD, Behçet's.
  • Drugs — oral contraceptive pill, sulfonamides, penicillins.
  • Pregnancy; lymphoma (rare); idiopathic.
• Investigate EN with throat swab or ASO titre, chest X-ray (sarcoid, TB), FBC, CRP; treat the cause, NSAIDs, rest and leg elevation.

IgG4-related Disease and Relapsing Polychondritis

• IgG4-related disease — fibro-inflammatory disease forming tumour-like swellings in one or many organs; usually older men:
  • Pancreas — autoimmune pancreatitis (painless obstructive jaundice — mimics pancreatic cancer; "sausage-shaped" pancreas).
  • Bile ducts (IgG4 sclerosing cholangitis), salivary and lacrimal glands (Mikulicz disease — swollen glands), orbit, retroperitoneal fibrosis (hydronephrosis), aorta (aortitis), kidneys (tubulointerstitial nephritis), lungs, thyroid (Riedel's).
  • Raised serum IgG4 (not always); biopsy — dense IgG4 plasma cells, storiform fibrosis, obliterative phlebitis.
  • Exclude cancer and lymphoma.
  • Treatment — steroids (rapid response), then rituximab or azathioprine for relapses; stents for obstruction.
• Relapsing polychondritis — recurrent inflammation of cartilage:
  • Ear — red, painful, swollen auricle sparing the earlobe (no cartilage) — "cauliflower ear" later.
  • Nose — saddle nose deformity.
  • Airway — laryngeal and tracheal involvement (hoarseness, stridor, airway collapse — the main cause of death).
  • Eyes (scleritis), joints (non-erosive arthritis), heart valves (aortic regurgitation), inner ear (deafness, vertigo).
  • Associated with myelodysplasia (VEXAS syndrome — older men, UBA1 mutation, macrocytosis, fever, chondritis).
  • Treatment — steroids, methotrexate, biologics.

Autoinflammatory Syndromes and Amyloidosis

• Autoinflammatory diseases — the innate immune system is overactive (no autoantibodies); recurrent fevers with inflammation:
  • Familial Mediterranean fever — Turkish, Armenian, Arab, Sephardic Jewish descent; MEFV gene; attacks of fever with peritonitis (mimics surgical abdomen), pleurisy, arthritis, erysipelas-like rash, lasting 1–3 days; colchicine prevents attacks and amyloidosis.
  • TRAPS (TNF receptor-associated periodic syndrome) — longer attacks (over a week), migratory myalgia, periorbital swelling.
  • CAPS (cryopyrin-associated) — cold-induced urticaria-like rash, fever, deafness — IL-1 blockers.
  • PFAPA (children) — periodic fever, aphthous ulcers, pharyngitis, cervical adenitis.
  • VEXAS syndrome — older men; fever, chondritis, skin lesions, lung inflammation, clots, macrocytic anaemia — haematology input.
• AA amyloidosis — deposition of serum amyloid A protein from long-standing uncontrolled inflammation (RA, AS, FMF, chronic infections — bronchiectasis, IV drug use, TB, IBD):
  • Kidneys — proteinuria and nephrotic syndrome, kidney failure; liver and spleen enlargement; gut.
  • Diagnosis — biopsy (fat, rectal, kidney) — Congo red staining, apple-green birefringence under polarised light; SAP scan.
  • Treatment — control the inflammation (biologics, colchicine for FMF); referral to the National Amyloidosis Centre.
• AL amyloidosis (light chains — myeloma and plasma cell disorders) affects the heart, kidneys, nerves, tongue (macroglossia) — haematology (see the Haematology chapters).

Emergencies and Systemic Diseases at a Glance

Spot the Diagnosis