What are the differential diagnoses for pustules, papules, and nodules on the feet, hands, and gluteal folds?

Differential Diagnoses for Pustules, Papules, and Nodules on Hands, Feet, and Gluteal Folds

The differential diagnosis for pustules, papules, and nodules in these specific locations includes hidradenitis suppurativa, pyoderma gangrenosum, pustular psoriasis (particularly palmoplantar pustulosis), Sweet's syndrome, cutaneous fungal infections, lymphomatoid papulosis, and infectious etiologies including bacterial and atypical mycobacterial infections.

Inflammatory/Autoimmune Conditions

Hidradenitis Suppurativa (HS)

• HS characteristically presents with comedones (paired), papules, pustules, nodules, cysts, and abscesses in flexural areas including the groin, perineum, buttocks, and gluteal folds 1
• The condition causes severe pain, pruritus, chronic discharge (serous, purulent, or blood-stained), and persistent malodor 1
• Diagnosis requires typical lesions in typical sites (axillae, groin, perineal region, perianal region, buttocks) with chronic and recurrent disease 1
• Long-standing disease results in fibrosis, dermal contractures, and scarring 1

Pyoderma Gangrenosum (PG)

• Initially presents as single or multiple erythematous papules or pustules, with subsequent necrosis leading to deep excavating ulcerations containing sterile purulent material 1
• Most commonly affects the shins but can occur anywhere on the body including the genitalia and gluteal region 1
• Lesions are often preceded by trauma through pathergy phenomenon 1
• Associated with inflammatory bowel disease in 0.6-2.1% of ulcerative colitis patients 1

Pustular Psoriasis

• Palmoplantar pustulosis (PPP) presents as localized disease affecting the palms and/or soles with sterile pustules 2
• This condition is debilitating and associated with impaired quality of life and psychiatric morbidity 2
• Acrodermatitis continua of Hallopeau affects digits/nail beds and threatens irreversible nail and bone damage 2
• Diagnosis can be challenging and may require dermatology consultation 2

Sweet's Syndrome

• Characterized by tender, red inflammatory nodules or papules, usually affecting the upper limbs, face, or neck 1
• Part of the acute neutrophilic dermatoses group, distinguished from pyoderma gangrenosum by appearance, distribution, and histology 1
• Strong predilection for women and patients with colonic involvement 1
• Systemic corticosteroids are effective treatment 1

Erythema Nodosum (EN)

• Presents as raised, tender, red or violet subcutaneous nodules of 1-5 cm diameter 1
• Commonly affects extensor surfaces of extremities, particularly anterior tibial areas 1
• Histology reveals non-specific focal panniculitis 1
• Treatment focuses on underlying disease with systemic steroids usually required 1

Infectious Etiologies

Fungal Infections

• Cutaneous fungal infections typically begin as erythematous papules that may become pustular and develop central ulceration with elevated borders 3
• Intertriginous areas (including gluteal folds) can present with hyperpigmentation and thickening 3
• Additional features include scaling and erythema at the periphery, distinguishing them from other conditions 3
• Diagnosis is confirmed through skin scraping with KOH preparation 3
• Topical antifungals are first-line for localized infections, with systemic therapy for extensive or resistant cases 3

Cutaneous Mold Infections

• Skin lesions can present as papules, nodules, or ulcers in immunocompromised patients 1
• Most common molds include Aspergillus, Mucormycosis, Scedosporium, and Fusarium species 1
• Skin biopsy should be performed for diagnosis with consideration of resection or debulking 1
• Voriconazole is the best therapeutic option for most mold infections 1

Nocardia Infections

• Cutaneous manifestations are usually limited to subcutaneous nodules or abscesses and panniculitis 1
• Soft tissue abscesses are frequently painless and described as cold to the touch 1
• SMX-TMP remains the treatment of choice 1
• Prolonged therapy (6-24 months) is important depending on dissemination and immunosuppression 1

Bartonella Infections (Cat Scratch Disease/Bacillary Angiomatosis)

• A papule or pustule develops 3-30 days following a scratch or bite, with subsequent lymphadenopathy 1
• Bacillary angiomatosis in immunocompromised patients presents as red papules or subcutaneous painful nodules 1
• Azithromycin is recommended: 500 mg day 1, then 250 mg for 4 days (patients >45 kg) 1

Erysipeloid

• Red maculopapular lesion develops 1-7 days after exposure to fish, marine animals, swine, or poultry, usually on fingers or hands 1
• Erythema spreads centrifugally with central clearing, may have blue ring with peripheral red halo 1
• Penicillin (500 mg qid) or amoxicillin (500 mg tid) for 7-10 days is recommended 1

Lymphoproliferative Disorders

Lymphomatoid Papulosis (LP)

• Chronic, recurrent, self-healing papulonodular eruption with histopathologic features of cutaneous T-cell lymphoma but often benign clinical course 1, 4
• Presents with recurrent grouped or disseminated papulonodular skin lesions that spontaneously regress within weeks or months 1
• Can affect hands and feet, though typically more generalized 4
• Diagnosis requires typical lesions with characteristic histology showing CD30+ cells 1
• Low-dose methotrexate is initial therapy for extensive or symptomatic disease 4

Key Diagnostic Approach

When evaluating these lesions, prioritize:

• Distribution pattern: Flexural involvement suggests HS; palmoplantar suggests pustular psoriasis; extensor surfaces suggest EN 1, 2
• Lesion characteristics: Paired comedones suggest HS; sterile pustules suggest pustular psoriasis or PG; self-healing papules suggest LP 1, 2
• Associated features: Chronic discharge and malodor suggest HS; pathergy suggests PG; scaling suggests fungal infection 1, 3
• Biopsy with culture: Essential for definitive diagnosis, particularly to exclude infectious etiologies 1, 3
• KOH preparation: Should be performed to rule out fungal infection in intertriginous areas 3

Critical Pitfalls to Avoid

• Do not use systemic corticosteroids for pustular psoriasis as they can trigger flares 2
• Do not assume purulent material indicates bacterial infection in PG—cultures are sterile unless secondary infection occurs 1
• Do not overlook immunosuppression as a risk factor for fungal and atypical infections 1, 3
• Do not dismiss self-healing lesions as benign without considering lymphomatoid papulosis, which carries risk of secondary lymphoma 1, 4