What autoimmune or autoinflammatory diseases are associated with sterile non-infected recurrent paronychia and felons?

Autoimmune and Autoinflammatory Diseases Associated with Sterile Recurrent Paronychia

Sterile recurrent paronychia and felons should prompt evaluation for SAPHO syndrome (synovitis, acne, pustulosis, hyperostosis, osteitis), DIRA/DITRA (deficiency of IL-1 receptor antagonist/IL-36 receptor antagonist), PAPA syndrome (pyogenic arthritis, pyoderma gangrenosum, and acne), and autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED). 1

Primary Autoinflammatory Syndromes to Consider

IL-1 Pathway Disorders

• DIRA (Deficiency of IL-1 Receptor Antagonist) and DITRA (Deficiency of IL-36 Receptor Antagonist) present with early-onset severe pustular skin disease, which can manifest as recurrent sterile paronychia 1
• These conditions require genetic testing for IL1RN and IL36RN mutations, as well as chromosomal analysis for deletions in the IL1 locus 1
• Treatment involves IL-1 antagonists (anakinra) or TNF inhibitors, along with corticosteroids 1

PAPA Syndrome

• PAPA syndrome (Pyogenic Arthritis, Pyoderma Gangrenosum, and Acne) presents with fevers associated with pyogenic arthritis, ulcerative skin lesions, and cystic acne that can involve the nail folds 1
• Mutational analysis of the PSTPIP1 gene should be evaluated when this constellation is present 1

SAPHO Syndrome

• SAPHO syndrome is part of the chronic non-bacterial osteitis (CNO) spectrum and can present with sterile inflammatory manifestations including pustular skin lesions (palmo-plantar pustulosis, psoriasis, severe acne) that may involve periungual tissues 1
• This condition predominantly affects adults and may present with bone inflammation alongside dermatological features including hidradenitis suppurativa and severe acne 1

Autoimmune Conditions to Evaluate

APECED (Autoimmune Polyendocrinopathy-Candidiasis-Ectodermal Dystrophy)

• APECED should be considered when chronic mucocutaneous candidiasis is present with polyendocrine autoimmunity 1
• There is a strong correlation between antibodies against IL-17A, IL-17F, and IL-22 with chronic mucocutaneous candidiasis in patients with autoimmune regulator (AIRE) mutations 1
• These patients may present with recurrent sterile paronychia as part of their broader autoinflammatory phenotype 1

IPEX and Related Immune Dysregulation Syndromes

• IPEX syndrome (immune dysregulation, polyendocrinopathy, enteropathy, X-linked) and related conditions including CD25 and ITCH deficiency should be considered when food/environmental allergies are present alongside recurrent inflammatory manifestations 1

Diagnostic Approach

Initial Evaluation

• Rule out infectious causes first through culture and microscopy, as chronic paronychia is frequently multifactorial with secondary bacterial or fungal colonization 2, 3
• Evaluate for other primary immunodeficiency disorders, malignancy, or autoimmune disease before diagnosing autoinflammatory syndromes 1

Laboratory Testing

• Obtain inflammatory markers (ESR, CRP) which are typically highly elevated in autoinflammatory conditions 4
• Consider autoimmune panel including ANA, RF, and anti-CCP if systemic autoimmune disease is suspected 4
• Test for anti-cytokine autoantibodies (anti-IL-17A, anti-IL-17F, anti-IL-22) if chronic mucocutaneous candidiasis is present 1

Imaging and Biopsy

• MRI or CT combined with nuclear imaging is recommended for initial evaluation if CNO/SAPHO syndrome is suspected 1
• Whole-body imaging can be considered for diagnostic and prognostic purposes in suspected CNO 1
• Skin biopsy may help differentiate inflammatory from infectious etiologies 2, 3

Critical Diagnostic Pitfalls

• Do not assume infection - chronic paronychia in the context of autoinflammatory disease is sterile and will not respond to antibiotics alone 2, 5
• Recognize that secondary colonization with bacteria or fungi can occur in chronically inflamed tissue, but this does not indicate primary infection 2, 3, 6
• Nonspecific autoantibodies (ANA, RF, anti-dsDNA) can be persistently or transiently present at mildly or moderately increased levels in autoinflammatory conditions, especially non-inflammasome defects 1
• Autoantibody positivity alone does not make a diagnosis - clinical context is paramount 4

When to Refer

• Refer to rheumatology or immunology when sterile recurrent paronychia occurs with systemic features (fever, arthritis, other skin manifestations) 4
• Genetic testing and specialized immunologic evaluation should be pursued through centers with expertise in autoinflammatory disorders 1
• Dermatology consultation should be obtained for suspected chronic paronychia unresponsive to standard treatment to investigate unusual causes 6