What are the complications of pemphigus vulgaris?

Complications of Pemphigus Vulgaris

Pemphigus vulgaris carries significant morbidity and mortality primarily from infection/sepsis, treatment-related adverse effects, and disease-related complications, with modern mortality rates of 1.4-7% when treated with corticosteroids and immunosuppressants. 1

Disease-Related Complications

Infection and Sepsis

• Infection is the leading cause of death in pemphigus vulgaris, accounting for the majority of mortality in treated patients 1, 2
• Sepsis represents a major fatal complication, responsible for 5 of 14 deaths in one large series 2
• Bacterial skin infections occur commonly (26 patients in one cohort of 159), with erosions serving as portals of entry 2
• Oral candidiasis develops frequently, particularly in patients on immunosuppressive therapy 3
• Herpes simplex and herpes zoster infections occur in 13% and 5% of rituximab-treated patients respectively 3
• Pneumocystis jirovecii pneumonia represents a serious opportunistic infection risk 3

Mucocutaneous Complications

• Extensive cutaneous ulceration can develop, with healing taking considerably longer than initial disease control 1
• Oral ulceration tends to heal more slowly than skin lesions, often being the last site to clear in mucocutaneous disease 1
• Scarring can occur, particularly when infection complicates the erosions 1
• Pain is a significant complication requiring both acute and maintenance analgesia 1

Nutritional and Functional Impact

• Severe oral involvement can impair eating and nutrition 1
• The disease causes significant pain and burning sensations, particularly during blister care 1

Treatment-Related Complications

Corticosteroid Adverse Effects

• Steroid diabetes develops in approximately 23% of patients on prolonged high-dose corticosteroids 2
• Arterial hypertension occurs in approximately 14% of patients 2
• Osteoporosis represents a major long-term complication 4
• Aseptic necrosis of the femoral head can occur with prolonged steroid use 4
• Cushing syndrome develops with chronic high-dose therapy 1
• Cataracts and glaucoma are ophthalmologic complications 4
• Optic nerve atrophy has been reported 4
• Proximal myopathy develops with prolonged use 1
• Peptic ulceration occurs as a gastrointestinal complication 1
• Weight gain is common 1
• Mood changes and psychiatric disturbances occur 1
• Adrenal suppression develops, with pituitary-adrenal suppression reported in 55% of patients on pulse therapy 1

Immunosuppressant-Related Complications

Cyclophosphamide complications:

• Amenorrhea occurs in 62% of menstruating females (18 of 29 patients) 1
• Azoospermia develops in male patients, causing secondary infertility 1
• Hemorrhagic cystitis occurs in 0.6% of patients 1
• Bladder malignancy risk increases with long-term use 1
• Alopecia is common 1
• Neutropenia can develop 1

Azathioprine complications:

• Myelosuppression occurs, particularly in patients with low TPMT activity 1
• Hepatotoxicity develops independent of TPMT activity 1
• Nausea is common 1
• Hypersensitivity reactions occur 1

Mycophenolate mofetil complications:

• Gastrointestinal disturbances are the most common side effect 1
• Lymphopenia can develop 1
• Anemia and thrombocytopenia occur 1

Rituximab complications:

• Infusion-related reactions occur in 58% of patients, though most are mild to moderate 3
• Hypogammaglobulinemia develops, with prolonged hypogammaglobulinemia in 16.4% of patients 3
• Late-onset neutropenia can occur 1
• Serious infections occur in 8-9% of patients 3
• Hepatitis B reactivation is a risk 1
• Progressive multifocal leukoencephalopathy from JC virus is a rare but serious complication 1

Cardiovascular Complications

• Cardiorespiratory failure is a major cause of death, accounting for 6 of 14 deaths in one series 2
• Cardiorespiratory diseases complicate treatment in approximately 14% of patients 2
• Tachycardia and hypertension can occur as infusion-related reactions 3

Mortality

• Historical mortality before corticosteroids was 75%, reduced to 1.4-7% with modern immunosuppressive therapy 1
• Mortality rates of 4-6% are reported in large series using pulse cyclophosphamide-dexamethasone therapy 1
• Mucosal-only disease has lower mortality (1-17%) compared to mucocutaneous disease (34-42%) 1
• The main causes of death are cardiorespiratory failure and sepsis 2

Psychological and Quality of Life Impact

• Patients require psychological support to cope with a chronic, painful, and visible disease 1
• The impact of treatment itself significantly affects quality of life 1
• Depression occurs in 18% of rituximab-treated patients compared to 11% on prednisone alone 3

Pregnancy-Related Complications

• Increased risk of fetal morbidity with gestational pemphigus vulgaris 1
• Higher preterm birth rates occur 1
• Low birthweight is more common 1
• Neonatal pemphigus develops in 45% of neonates, though all cases resolve within 4 weeks 1
• Five neonatal deaths have been reported in the literature 1
• Intrauterine growth retardation is linked to systemic corticosteroid use 1