What are the treatments for inflammatory conditions affecting the subcutis, such as panniculitis and erythema nodosum?

Inflammatory Conditions Affecting the Subcutis: Detailed Overview and Treatment

Erythema Nodosum

For erythema nodosum, NSAIDs are the cornerstone of treatment, with systemic corticosteroids reserved for severe cases after excluding infectious causes, and immunomodulators (azathioprine or TNF-alpha inhibitors) used for frequent relapses or IBD-associated disease. 1

Clinical Presentation

• Raised, tender, red or violet subcutaneous nodules measuring 1-5 cm in diameter, typically bilateral and symmetrical on the anterior tibial areas 2, 1
• Systemic symptoms include fever, malaise, extreme fatigue persisting weeks to months, and symmetrical arthralgias affecting distal lower extremities without joint effusions 1
• Lesions evolve from bright red to livid red/purplish, then yellow-greenish resembling deep bruises over days 3
• Never ulcerates and heals without scarring or atrophy 3, 4

Etiologies

• Inflammatory bowel disease (ulcerative colitis and Crohn's disease) occurs in 4.2-7.5% of IBD patients 2, 1
• Streptococcal pharyngitis is the most common identifiable infectious cause 4
• Behçet's disease with oral and genital ulcers 1
• Fungal infections: coccidioidomycosis (endemic southwestern US) and histoplasmosis 1
• Sarcoidosis, medications (oral contraceptives, antibiotics), pregnancy, malignancy 3, 4
• Up to 55% of cases are idiopathic 5

Diagnostic Approach

• Diagnosis is primarily clinical based on characteristic features; biopsy is not usually necessary except in atypical cases 1, 3
• When biopsy is performed, obtain deep incisional or excisional specimens showing septal panniculitis without vasculitis, with Miescher's radial granulomas (small histiocytes arranged radially around a central cleft) 3, 4
• Laboratory evaluation: complete blood count with differential, ESR or CRP, streptococcal testing (throat culture, rapid antigen test, ASO titer), and risk stratification for tuberculosis with PPD/chest radiography as indicated 4

Treatment Algorithm

First-line symptomatic treatment:

• NSAIDs (indomethacin, naproxen, oxyphenbutazone) for pain and inflammation 1, 3
• Bed rest and supportive care 3, 4
• Compression stockings (20-30 mmHg) worn daily provide lasting clinical resolution and reduce tenderness 6

Second-line for persistent symptoms:

• Potassium iodide for enhanced analgesia and resolution 3, 7
• Colchicine, particularly when associated with Behçet's syndrome 1, 7

Third-line for severe cases or IBD-associated disease:

• Systemic corticosteroids, but only after excluding infectious causes (particularly tuberculosis) 2, 1, 3
• For IBD-associated EN with active disease, treat the underlying bowel inflammation with systemic steroids 2

Fourth-line for frequent relapses or refractory disease:

• Azathioprine for immunomodulation 2, 1
• TNF-alpha inhibitors (infliximab or adalimumab) for resistant cases associated with IBD 2, 1
• Hydroxychloroquine may be added for sarcoidosis-associated EN 1

Critical Pitfalls

• Never start corticosteroids before excluding tuberculosis and other infections 1, 3
• Monitor for persistent underlying disease activity in IBD or sarcoidosis, as recurrent EN indicates ongoing systemic inflammation 1
• EN associated with IBD typically occurs during active disease flares and requires treatment of the underlying bowel disease 2

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Alpha-1 Antitrypsin Deficiency-Associated Panniculitis

For AAT deficiency-associated panniculitis, augmentation therapy with purified human AAT or fresh frozen plasma is the rational and effective treatment, with dapsone as adjunctive therapy. 2

Clinical Presentation

• Painful, hot, red, tender nodules on thighs and/or buttocks in young adults (mean age 40 years), with equal sex distribution 2
• Subsequent ulcerations with drainage of clear, yellow, oily, odorless, sterile fluid 2
• Approximately one-third of cases are precipitated by trauma 2
• Can be lethal, particularly with coexisting cirrhosis or emphysema 2

Diagnostic Features

• Requires deep excisional specimens with large amounts of tissue for proper histopathological evaluation 2
• Histology shows fat necrosis, normal-appearing fat juxtaposed to inflammatory and necrotic panniculus, fragmentation and loss of elastic tissue in inflamed areas 2
• Vasculitis is infrequent except secondary to necrosis 2
• Most cases occur in PIZZ phenotype (severe deficiency), but PIMZ, SS, and MS phenotypes also reported 2

Treatment

• Augmentation therapy with purified human AAT or fresh frozen plasma to restore plasma and local tissue AAT levels 2
• Dapsone, either alone in less severe cases or combined with augmentation therapy 2
• Liver transplantation led to permanent cure in one case by restoring plasma AAT levels 2
• Corticosteroids, antibiotics, and cytostatic drugs are ineffective 2
• Family screening and antismoking counseling are essential 2

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Pyoderma Gangrenosum

For pyoderma gangrenosum in ulcerative colitis patients, infliximab should be considered if rapid response to corticosteroids cannot be achieved, as it demonstrates 69% response rate and 31% remission rate at 6 weeks. 2

Clinical Presentation

• Initially single or multiple erythematous papules or pustules, progressing to deep excavating ulcerations with sterile purulent material 2
• Most common sites are shins and adjacent to stomas 2
• Often preceded by trauma at the site (pathergy phenomenon) 2
• Occurs in 0.6-2.1% of UC patients 2

Treatment Hierarchy

First-line:

• Systemic corticosteroids (traditionally first-line with best clinical experience) 2

Second-line for refractory cases:

• Intravenous ciclosporin 2
• Oral or intravenous tacrolimus 2

Preferred for rapid response:

• Infliximab 5 mg/kg demonstrates significantly more improvement at week 2 compared to placebo (46% vs 6%, p=0.025) 2
• Overall response rate 69%, remission rate 31% at week 6 with infliximab 2
• Response rate exceeds 90% in patients with disease duration less than 12 weeks, but drops below 50% for disease present more than 3 months 2

Alternative therapies:

• Topical tacrolimus (specialist advice recommended) 2
• For peristomal PG, stoma closure may lead to resolution 2

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Sweet's Syndrome

For Sweet's syndrome associated with ulcerative colitis, systemic corticosteroids are effective treatment. 2

Clinical Features

• Tender, red inflammatory nodules or papules affecting upper limbs, face, or neck 2
• Part of acute neutrophilic dermatoses group (includes pyoderma gangrenosum) but distinguished by appearance, distribution, and histology 2
• Strong predilection for women and patients with colonic involvement and other extraintestinal manifestations 2
• Mostly associated with active disease 2

Treatment

• Systemic corticosteroids reported as effective 2

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Anti-TNF-Induced Skin Inflammation

Anti-TNF treatment can induce paradoxical skin inflammation as a class-drug effect, which is usually reversible upon drug cessation. 2

Management

• Recognize as class-drug effect affecting all TNF-alpha inhibitors 2
• Refer to dermatologist when diagnosis is uncertain 2
• Usually reversible with drug cessation 2