What is the recommended first‑line therapy, dosing, and monitoring for a middle‑aged adult with pemphigus vulgaris?

First-Line Therapy for Pemphigus Vulgaris

Start oral prednisolone at 1 mg/kg/day combined with an adjuvant immunosuppressant (azathioprine, mycophenolate mofetil, or rituximab) immediately at diagnosis to maximize remission rates and minimize long-term corticosteroid toxicity. 1

Initial Corticosteroid Dosing

• Begin with oral prednisolone 1 mg/kg/day (or equivalent corticosteroid) for most cases of moderate-to-severe pemphigus vulgaris 1
• For milder, limited disease, consider starting at 0.5–1 mg/kg/day 1
• Increase dose by 50–100% increments every 5–7 days if new blisters continue to form 1
• For severe or rapidly progressive disease, consider pulsed intravenous methylprednisolone (typically 500–1000 mg/day for 3 days) followed by oral prednisolone 1 mg/kg/day 1
• Clinical improvement typically occurs within days, with cessation of new blisters averaging 2–3 weeks and complete healing by 3–8 weeks 1

Adjuvant Immunosuppressant Selection

The 2017 British Association of Dermatologists guidelines now recommend combining corticosteroids with an adjuvant immunosuppressant from the outset, based on landmark RCT evidence showing rituximab plus short-term prednisolone achieved 89% complete remission off all therapy at 2 years versus only 28% with prednisolone alone 1. This represents a paradigm shift from earlier guidelines that were more equivocal about adjuvant use 1.

First-Line Adjuvant Options:

• Azathioprine 2–3 mg/kg/day (check TPMT enzyme activity before initiating) 1
• Mycophenolate mofetil 2–3 g/day (divided doses) 1
• Rituximab using rheumatoid arthritis protocol: two 1000 mg IV infusions separated by 2 weeks, combined with tapering glucocorticoids 1, 2

Important caveat: Adjuvant drugs require 6–8 weeks to show clinical effect 3, so they are primarily for maintenance and steroid-sparing rather than acute remission induction 1.

Corticosteroid Tapering Strategy

• Begin tapering only after remission is induced and maintained, defined as absence of new blisters and healing of the majority of existing lesions (skin and mucosal) 1
• Aim to reduce prednisolone to ≤10 mg/day as the maintenance target 1
• Taper gradually; premature withdrawal leads to 47% relapse rates when stopped after only 1 year 1
• Accept occasional new blisters during taper—this indicates appropriate dosing rather than overtreatment 1

Essential Baseline Monitoring and Prophylaxis

Before Starting Treatment:

• Complete blood count, comprehensive metabolic panel (creatinine, electrolytes, glucose, liver enzymes) 1
• Assess osteoporosis risk immediately and initiate bone protection for long-term corticosteroid therapy 1
• TPMT enzyme testing if azathioprine is planned 1
• G6PD testing if dapsone is considered 1
• Hepatitis B, C, and HIV serologies if immunosuppression is planned 1
• Pregnancy test for women of childbearing age 1
• Consider baseline ophthalmologic examination (cataract and glaucoma screening) for anticipated long-term corticosteroid use 1

Infection Prevention:

• Daily cleansing with antibacterial products to reduce colonization during intensive immunosuppression 3
• Systematic surveillance for infection: regular temperature monitoring, wound inspection, assessment for systemic symptoms 3
• Obtain bacterial and viral cultures/swabs of erosions when infection is suspected 3
• Initiate systemic antibiotics promptly for confirmed or strongly suspected infections 3
• Consider prophylactic antimicrobials (particularly PCP prophylaxis with trimethoprim-sulfamethoxazole) during and following rituximab treatment 2

Adjunctive Mucosal Management

For oral involvement (present in nearly all cases 1):

• Betamethasone sodium phosphate 0.5 mg dissolved in 10 mL water as a 2–3 minute rinse-and-spit solution, 1–4 times daily 4, 5
• Clobetasol 0.05% ointment mixed 50:50 with Orabase applied to localized lesions on dried mucosa 4, 5
• Gelclair mucoprotectant gel applied three times daily for pain relief 5
• Benzydamine hydrochloride 0.15% oral rinse before eating or toothbrushing 4, 5
• Soft diet and soft toothbrushes to minimize trauma 4
• Warm saline or antiseptic mouthwashes (0.2% chlorhexidine or 1.5% hydrogen peroxide) twice daily 5

Pain Management

• Comprehensive scheduled analgesia with baseline and breakthrough dosing is essential 3
• Severe oral erosions cause intense odynophagia requiring scheduled analgesics, not just as-needed dosing 3
• Provide short-acting analgesic "boosts" during dressing changes or painful procedures 3
• Refer to pain management team if pain remains uncontrolled with standard regimens 3

Second-Line Options for Treatment Failure

If inadequate response to first-line adjuvant (azathioprine, mycophenolate mofetil, or rituximab):

• Switch to an alternate corticosteroid-sparing agent from the first-line options 1
• Mycophenolic acid 720–1080 mg twice daily if gastrointestinal intolerance to mycophenolate mofetil 1

Third-Line Therapies

For refractory disease, consider multidisciplinary team consultation for:

• Cyclophosphamide 1
• Intravenous immunoglobulin (IVIG) 1
• Immunoadsorption or plasmapheresis 1
• Methotrexate 1

Common Pitfalls to Avoid

• Do not delay adjuvant immunosuppressant initiation—the 2017 RCT evidence strongly supports early combination therapy rather than sequential addition 1
• Do not taper corticosteroids too rapidly—maintain remission for adequate duration before tapering to avoid the 47% relapse rate seen with premature withdrawal 1
• Do not ignore infection surveillance—immunosuppressed patients require systematic monitoring and low threshold for cultures and empiric antibiotics 3
• Do not undertake treatment without baseline osteoporosis assessment—bone protection must begin immediately with long-term corticosteroid therapy 1
• Do not forget mucosal care—topical corticosteroids and supportive measures are critical adjuncts since oral involvement occurs in almost all cases 1, 4

Long-Term Prognosis and Treatment Withdrawal

• Complete remission off all therapy is achievable: 38% at 3 years, 50% at 5 years, and 75% at 10 years from diagnosis 1
• Treatment withdrawal should be cautious and gradual, not premature 1
• Mortality has dramatically improved since the introduction of corticosteroids, with recent studies showing zero mortality in appropriately treated cohorts 1