What causes pustules?

Causes of Pustules

Pustules are caused by either infectious agents (bacteria, fungi, viruses, parasites) or non-infectious inflammatory processes, with the most common infectious cause being Staphylococcus aureus in follicular infections, while non-infectious causes include drug reactions, psoriasis, and immune-mediated inflammatory conditions. 1, 2

Infectious Causes

Bacterial Infections

• Follicular infections are the most common bacterial cause, where S. aureus invades hair follicles causing furuncles (boils) that present as inflammatory nodules with overlying pustules through which hair emerges 1
• Impetigo begins as papules that evolve into vesicles and then pustules, caused by S. aureus or streptococci, with nonbullous impetigo forming characteristic thick crusts over 4-6 days 1
• Gram-negative folliculitis can develop during acne treatment with tetracycline, showing in vitro resistance to ampicillin and requiring co-trimoxazole and topical gentamicin 3
• Glanders (Burkholderia mallei) causes ulcerating nodular pustular lesions with systemic symptoms, though this is rare and primarily affects those with animal contact 1
• Plague (Yersinia pestis) can present with pustules at the portal of entry in bubonic plague, along with tender regional lymphadenopathy 1

Fungal Infections

• Tinea capitis can present with diffuse pustular patterns showing patchy alopecia with scattered pustules or low-grade folliculitis, often with painful regional lymphadenopathy 1
• Kerion represents a severe inflammatory response to dermatophyte infection, presenting as a painful, boggy mass studded with pustules and matted with thick crust 1

Other Infectious Agents

• Certain viruses and parasites can provoke pus formation in skin, though bacteria remain the most common infectious cause 2

Non-Infectious Inflammatory Causes

Drug-Induced Pustules

• EGFR inhibitors (cetuximab, erlotinib, afatinib, osimertinib) cause papulopustular eruptions in 75-90% of patients, typically appearing on face, scalp, upper chest and back within days to weeks of therapy initiation 1
• MEK inhibitors (trametinib, binimetinib, cobimetinib) cause similar papulopustular eruptions in 74-85% of patients 1
• Acute generalized exanthematous pustulosis results from various medications causing generalized pustular eruptions 4
• The pustular eruption from these drugs is primarily an inflammatory process driven by keratinocyte-induced secretion of chemokines and cytokines, with secondary bacterial colonization occurring in up to 38% of cases 1

Psoriasis Variants

• Pustular psoriasis occurs when neutrophil collections in the stratum corneum become large enough to be clinically apparent as pustules 1
• Generalized pustular psoriasis (von Zumbusch variant) presents with widespread pustules on an erythematous background, accompanied by fever and toxicity 1
• Localized pustular psoriasis affects palms and soles, with or without classic plaque-type disease elsewhere 1

Inflammatory Bowel Disease-Associated

• Pyoderma gangrenosum initially presents as erythematous papules or pustules that rapidly become deep excavating ulcerations with violaceous edges, occurring in 0.6-2.1% of ulcerative colitis patients 1

Other Inflammatory Conditions

• Acne vulgaris in its pustular form has bacteriologically sterile pustules despite the inflammatory appearance 2, 4
• Rosacea and perioral dermatitis cause pustules on the face 4
• Subcorneal pustular dermatosis causes generalized pustular eruptions in adults 4
• Eosinophilic folliculitis in HIV/AIDS patients presents with severely pruritic, sterile, eosinophilic pustules on chest, proximal extremities, head and neck 4

Pathophysiology of Non-Infectious Pustules

The unifying mechanism involves keratinocyte-myeloid synergy (KMS), where activated neutrophils microinvade epidermal or adnexal epithelia driven by IL-17/IL-23, IL-36/IL-36RN, or IL-1/caspase-activated pathways. 5

• IFNα controls production of chemoattractants (IL-8, LTB4) that recruit neutrophils 5
• Physical barriers like the stratum corneum establish chemotactic gradients that trap migrating neutrophils, facilitating pustule formation 5
• EGFR inhibitors impair expression of skin antimicrobial peptides, increasing susceptibility to bacterial superinfection 1

Critical Diagnostic Distinction

The presence or absence of bacterial infection determines treatment: infectious pustules require antimicrobial therapy targeting the specific pathogen, while non-infectious pustules require treatment of the underlying inflammatory condition, not antibiotics. 1, 2

• Culture of pustule contents distinguishes bacterial infection from sterile inflammatory pustules 1
• Clinical context (medication history, underlying disease, distribution pattern) guides initial assessment 1, 4
• Gram stain and culture are essential when infection is suspected, particularly in furuncles, carbuncles, or when systemic symptoms are present 1, 6