ImmunologyTier 1Medical Sciences concept

Secondary immunodeficiency from chronic corticosteroid use - typical infections

Core concept

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Glucocorticoid receptor -> inhibits NF-kB and AP-1

dec IL-1, IL-2, IL-6, TNF, IFN-gamma
dec T-cell number and function (CD4 most) - the dominant defect
dec macrophage killing and antigen presentation
dec monocytes, eosinophils, lymphocytes
NEUTROPHILIA - demargination + delayed apoptosis, but dec chemotaxis and dec transmigration
dec collagen, dec fibroblast function -> impaired wound healing, thin skin

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The neutrophil count rises while neutrophil function falls - a high count on steroids is not reassurance
Steroids also blunt fever and mask peritonism -> serious infection presents late and looks mild

The threshold that matters

Prednisolone >=20 mg/day for >=14 days (or >=2 mg/kg/day in small children) = significant immunosuppression
- Live vaccines contraindicated; defer until >=1 month after stopping
>=20 mg/day for >=4 weeks (some use >=16 mg/day) -> PJP prophylaxis, especially with a second agent (cyclophosphamide, rituximab, calcineurin inhibitor) or lymphopenia
Cumulative dose and concurrent agents matter more than the daily dose alone

Characteristic infections

Category	Organisms
Bacterial	Staph aureus, Gram-negatives, Listeria, Nocardia, Legionella
Fungal	Pneumocystis jirovecii, Candida (oral/oesophageal), Aspergillus, Cryptococcus
Mycobacterial	Reactivation TB, non-tuberculous mycobacteria
Viral	VZV reactivation (shingles, disseminated), HSV, CMV, hepatitis B reactivation
Parasitic	Strongyloides hyperinfection / disseminated strongyloidiasis - steroids directly accelerate the autoinfective cycle; mortality is high and it can occur decades after exposure

Screening before starting long-term steroids

Quantiferon/TST for latent TB; HBsAg + anti-HBc; HIV; strongyloides serology if any tropical/endemic residence (northern Australia, SE Asia, Africa)
Treat latent TB and give HBV antiviral prophylaxis before immunosuppression

Prescribe alongside the steroid, not after the complication
- PJP prophylaxis - co-trimoxazole 160/800 mg three times weekly (alternatives: dapsone, atovaquone, nebulised pentamidine)
- Calcium, vitamin D, and bisphosphonate for glucocorticoid-induced osteoporosis when >=7.5 mg/day for >=3 months
- Non-live vaccines - influenza, COVID, pneumococcal, Shingrix (recombinant, safe)
- Ivermectin for strongyloides if serology positive or exposure likely
Other secondary immunodeficiencies worth naming alongside: haematological malignancy (CLL, myeloma - hypogammaglobulinaemia), rituximab (prolonged hypogammaglobulinaemia), protein loss (nephrotic syndrome, protein-losing enteropathy), malnutrition, splenectomy, diabetes, CKD, HIV
Do not stop steroids abruptly - adrenal suppression coexists with the immunosuppression; stress dosing during infection

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