01Role and principlesWho benefits and the main preventive aims.
Immune-modifying treatment alters both susceptibility and presentation. Corticosteroids suppress broad cellular responses; methotrexate can reduce marrow reserve; ciclosporin impairs T-cell signalling; TNF blockade weakens granuloma control; JAK inhibition increases herpes-zoster and serious-infection risk; and barrier disease creates portals of entry. Age, frailty, diabetes, chronic lung or kidney disease, lymphopenia, neutropenia, malnutrition and combining agents can outweigh the risk of one drug in isolation. A recently stopped biologic can remain active for weeks or months.
Prevention begins before the first dose. Record infection and exposure history, examine unresolved wounds, perform agent-specific TB, viral and laboratory screening, review dental or device infection where relevant and reconcile vaccines. Influenza, COVID-19, pneumococcal and recombinant zoster vaccines are non-live, although timing before treatment can improve response. Live vaccines may cause disease during substantial immune suppression and require the minimum interval specified by the Green Book and the selected drug. Household contacts can usually receive routine vaccines, with specific precautions for live products.
During treatment, safety-net by syndrome rather than temperature alone. A person may have invasive infection without marked erythema, pus, fever, leukocytosis or CRP elevation. Examine the whole skin, mucosae, eyes and lines; compare photographs or marked margins; and ask about medicines started for a presumed infection. Withholding an immune modifier is only one part of care: source control, correctly dosed antimicrobial therapy, renal adjustment, cultures, physiological support and a documented restart decision determine outcome.
Key points
- Define the regimen precisely: infection risk depends on mechanism, dose, duration, combination treatment, comorbidity and residual drug half-life rather than the label immunosuppressed alone.
- Ask about tuberculosis, hepatitis, HIV, previous varicella or zoster, recurrent HSV, chronic wounds, diabetes, travel, exposure and vaccination before treatment begins.
- Complete indicated vaccines before immune suppression where possible; non-live vaccines are generally safe, whereas live vaccines require Green Book and agent-specific timing.
- Teach people to report fever, rapidly changing painful skin, grouped vesicles, eye symptoms, oral ulcers, cough, dysuria or diarrhoea early because treatment can blunt typical inflammation.
- Bacterial cellulitis and impetigo, dermatophyte or Candida infection, HSV and varicella-zoster are common; atypical mycobacteria, invasive fungi and other opportunists need targeted sampling and specialist care.
- A localised eruption can announce systemic disease: multidermatomal zoster, eczema herpeticum, ecthyma gangrenosum and necrotising infection must not be managed as routine dermatitis.
- Withhold methotrexate, ciclosporin, a biologic or a JAK inhibitor during a serious infection and seek the prescribing team's restart plan; a long half-life means risk does not stop immediately.
- Do not abruptly stop long-term systemic corticosteroid during infection; assess adrenal suppression and provide the usual dose or stress-dose replacement while treating sepsis.
- Check interactions before prescribing: trimethoprim or co-trimoxazole can cause severe marrow toxicity with methotrexate, while macrolides and azoles can raise ciclosporin exposure.
- Antimicrobial prophylaxis is risk-stratified for a defined pathogen and regimen; routine antibiotics for every immunosuppressed person promote resistance and do not replace rapid assessment.
02Assessment and patient selectionRisk features, eligibility and important cautions.
Expanding warmth, tenderness, swelling, crust, purulence or lymphangitis around fissures, ulcers, eczema, surgery or injection sites suggests bacterial infection, but erythema can be muted.
Pain out of proportion, rapid progression, oedema beyond visible change, bullae, dusky colour, anaesthesia, crepitus or shock demands immediate surgical assessment.
Unilateral dermatomal pain and vesicles may disseminate across dermatomes; forehead, nasal-tip, eye pain, red eye or visual change indicates ophthalmic risk.
Clusters of monomorphic painful punched-out erosions, fever or malaise on eczematous skin suggest disseminated HSV and require immediate systemic antiviral treatment.
Asymmetric scaly advancing edges, satellite pustules, maceration or nail disease may be altered by corticosteroid use and should be sampled before further escalation.
Persistent nodules, ulcers, draining sinuses, unusual sporotrichoid spread or failure of standard antibiotics suggests deep fungus, atypical mycobacteria or another uncommon organism.
New functional decline, confusion, tachypnoea, hypotension or rigors can be more informative than absent fever, normal neutrophils or modest CRP after immune suppression.
03Baseline assessmentMeasurements that guide the plan and track progress.
Read from the initial assessment onwards. Tests may run in parallel in urgent care; first-line, preferred, confirmatory, definitive and gold-standard labels appear only when the chapter explicitly states them.
- 01
Baseline infection and vaccine assessmentFirst step - Why
- Identify preventable and reactivatable infection before immune suppression.
- Interpretation and limitations
- Record TB exposure, hepatitis and HIV risk, varicella history, travel, recurrent infection and vaccines; order IGRA, hepatitis B and C, HIV or parasite testing according to agent and epidemiology.
- 02
Full blood count and differential - Why
- Detect neutropenia, lymphopenia or treatment-related marrow toxicity.
- Interpretation and limitations
- Compare with baseline and trend; fever with significant neutropenia is an emergency, while a normal count does not exclude invasive infection on corticosteroids or targeted therapy.
- 03
Renal, liver and inflammatory profile - Why
- Assess organ involvement and dose antimicrobials safely.
- Interpretation and limitations
- Urea, electrolytes, eGFR, liver tests and CRP establish severity and interactions, but a blunted inflammatory response cannot reassure against sepsis.
- 04
Lesion-directed microbiology - Why
- Obtain the organism from the most informative active site.
- Interpretation and limitations
- Send bacterial culture from pus or debrided tissue, HSV or VZV PCR from a fresh vesicle base and skin, hair or nail scraping for microscopy and culture; superficial swabs alone can identify colonisers.
- 05
Blood cultures and lactate - Why
- Assess suspected sepsis or disseminated infection before antimicrobials when feasible.
- Interpretation and limitations
- Take appropriate sets promptly, including from a line when relevant, but never delay treatment in shock; normal lactate does not exclude a dangerous focal infection.
- 06
Biopsy for histology and tissue culture - Why
- Investigate persistent, deep, necrotic or atypical lesions.
- Interpretation and limitations
- Coordinate dermatology, microbiology and histopathology so separate fresh tissue reaches bacterial, mycobacterial and fungal culture and fixed tissue reaches histology; formalin destroys culture viability.
04InterventionsLifestyle, treatment and escalation options.
01First-line preventionReduce risk before treatmentFirst stepFirst lineA systemic immune-modifying medicine is planned or intensified.+
- 1Define drug, dose, combinations and expected duration and identify age, comorbidity, exposure, wound, travel and previous-infection modifiers.
- 2Complete the agent-specific TB, viral and laboratory screen, treat active infection and refer latent TB or hepatitis risk before starting.
- 3Offer indicated non-live vaccines and arrange any required live vaccine before therapy with the correct Green Book and SmPC interval.
- 4Give written early-warning, contact, medicine-withholding, food, travel, occupational and household-vaccine advice and record the responsible service.
02Urgent infectionTreat first and define severityThere is rapid skin progression, systemic illness, disseminated vesiculation or organ involvement.+
- 1Assess ABCDE, sepsis physiology, extent, pain, mucosae, eyes, neurological features and immune regimen without waiting for fever or CRP.
- 2Obtain blood and lesion samples when this will not delay treatment, then give syndrome-appropriate antimicrobial or antiviral therapy with renal adjustment.
- 3EscalationEscalate immediately to surgery for possible necrotising infection, ophthalmology for ocular zoster and infection or dermatology specialists for dissemination.
- 4Withhold relevant immune modifiers after prescriber discussion, continue physiological corticosteroid cover and document restart criteria after clinical resolution.
03Persistent lesionLook beyond routine organismsA lesion progresses despite appropriate standard therapy or has nodular, deep or sporotrichoid morphology.+
- 1Recheck diagnosis, adherence, antimicrobial dose, source control, resistance, foreign material and the full degree of immune compromise.
- 2Stop repeatedly swabbing the surface and obtain imaging or a deep biopsy with separately handled tissue for histology and broad microbiological culture.
- 3Ask microbiology or infectious diseases to direct incubation, molecular testing and prolonged therapy for fungi, mycobacteria or other opportunists.
04Restart decisionBalance infection resolution and inflammatory flareAn immune-modifying medicine was withheld during infection.+
- 1Confirm clinical response, source control, antimicrobial course and recovery of affected organs and blood counts rather than using elapsed days alone.
- 2Review whether the infection exposed an avoidable dose, interaction, vaccine gap, wound problem or need for pathogen-specific prophylaxis.
- 3Agree restart, switch or dose modification with the prescribing specialist and give the patient a single written plan that names warning signs.
05Medicines and treatment safetyRegimens, contraindications and review points.
Valaciclovir
For immunocompetent adult shingles, 1 g orally three times daily for 7 days; use the specialist regimen for immunocompromise and reduce by renal function.Start promptly in high-risk or immunosuppressed disease; use intravenous aciclovir for severe, disseminated or unable-to-absorb infection, maintain hydration and adjust for kidney impairment to prevent neurotoxicity.
Intravenous aciclovir
For herpes zoster in an immunocompromised adult, 10 mg/kg intravenously every 8 hours, infused over 1 hour, with renal and weight-based adjustment under specialist care.Check renal function, hydration and interacting nephrotoxins; crystalluria, acute kidney injury and confusion or tremor can occur, and suspected ocular or CNS disease needs parallel specialist management.
Flucloxacillin
For uncomplicated adult cellulitis, 500 mg to 1 g orally four times daily for 5 to 7 days when the local pathway and allergy history support it.Sepsis, orbital infection, necrosis, bites, water exposure, purulence, MRSA risk or profound immune compromise changes route or spectrum; check penicillin allergy, liver risk and culture results.
06Targets, monitoring and follow-upResponse, safety and longer-term review.
- At each treatment review, ask directly about interval antibiotics, shingles or cold sores, wounds, dental infection, travel, contacts and hospital attendance rather than relying on spontaneous reporting.
- Trend the drug-specific FBC, renal and liver schedule and bring testing forward after illness, dehydration, an interacting medicine or an unexpected skin infection.
- Review vaccine status annually and before travel or treatment switch; record product, date and whether it is live or non-live before advising timing.
- Mark and photograph spreading infection with consent, reassess physiology and pain within the clinical timescale, and escalate if the edge advances or systemic features emerge.
- After a serious or recurrent infection, document organism, source, antimicrobial susceptibility, withheld doses, recovery and a named specialist restart decision.
- If prophylaxis is prescribed, monitor the intended endpoint, adherence, renal or marrow toxicity, interactions and breakthrough infection instead of continuing it without review.
07Special situationsVariants, exceptions and circumstances that change the usual approach.
No fever is not reassuring
Corticosteroids, cytokine blockade and neutropenia can uncouple invasive infection from fever, pus, leukocytosis and a large CRP response.
Withholding has delayed biology
A biologic can retain clinically relevant activity after a dose is skipped, so antimicrobial urgency and infection-control decisions cannot wait for washout.
Steroids need physiological cover
Stopping long-term prednisolone during sepsis can precipitate adrenal crisis; treat infection while preserving or increasing replacement according to acute-illness guidance.
Tissue handling determines yield
Deep infection diagnosis fails when every biopsy enters formalin; microbiology needs a separate sterile fresh specimen and advance notice for specialist cultures.
Prophylaxis follows a defined risk
Pneumocystis, TB, hepatitis B, HSV or zoster prevention is linked to regimen and host factors, not prescribed indiscriminately for any immunosuppressant.
Interactions can mimic progression
Marrow failure from trimethoprim plus methotrexate or ciclosporin toxicity after a macrolide can add systemic illness to the original infection.
08Common pitfallsFrequent interpretation and management errors.
- 01
Reassuring a hypotensive or confused patient because immunosuppression has suppressed fever and CRP.
- 02
Treating dermatomal forehead vesicles by telephone without asking about eye pain, redness, photophobia or vision.
- 03
Stopping long-term prednisolone abruptly when withholding methotrexate or a biologic for sepsis.
- 04
Prescribing trimethoprim or co-trimoxazole to a methotrexate-treated person without recognising potentially fatal marrow toxicity.
- 05
Escalating topical corticosteroid over tinea incognito without scraping an advancing asymmetric edge.
- 06
Sending the whole biopsy in formalin when deep fungal or mycobacterial culture is required.
- 07
Giving a live vaccine during significant immune suppression without checking Green Book and drug-specific timing.
- 08
Restarting treatment automatically after the last antibiotic dose despite unresolved source, organ injury or cytopenia.