Strength of recommendation (level of evidence)a |
Drug |
Indication(s) |
Advantages |
Disadvantages |
Principal side-effects |
B (1+) |
Oral corticosteroids |
The cornerstone of therapy; effective; optimum dosing schedule not known |
Effective; rapid onset; oral administration; inexpensive |
Side-effect profile |
Diabetes; osteoporosis; adrenal suppression; peptic ulceration; weight gain; increased susceptibility to infection; mood changes; proximal myopathy; Cushing syndrome; cataracts |
B (1+) |
Azathioprine |
Commonly used in combination with oral corticosteroids for steroid-sparing effect; monotherapy may be possible for mild disease |
Oral administration; inexpensive |
Slow onset; side-effect profile |
Myelosuppression and nausea (related to thiopurine methyltransferase activity); hepatotoxicity and hypersensitivity reactions (unrelated to thiopurine methyltransferase activity); increased susceptibility to infection |
B (1+) |
Mycophenolate mofetil |
An alternative to azathioprine and cyclophosphamide |
Generally well tolerated and possibly less toxic than other immunosuppressive agents |
Slow onset |
Gastrointestinal disturbances (mycophenolic acid may be used as an alternative); lymphopenia; anaemia; neutropenia; thrombocytopenia; increased risk of infections |
B (1+) |
Rituximab |
Patients intolerant of or refractory to conventional corticosteroids together with adjuvant immunosuppression |
Effective; long-lasting effect |
Cost; infection risk; infusion reactionsb |
Risk of infection; risk of reactivation of hepatitis B; risk of precipitation of progressive multifocal leucoencephalopathy due to the JC virus. Hypogammaglobulinaemia (rare); late-onset neutropenia; development of neutralizing antibodies. Infusion reactions are generally mild; anaphylaxis is rare |
B (2+) |
Pulsed cyclophosphamide and dexamethasone or methylprednisolone |
Consider for severe or recalcitrant PV; repeated courses; may not be practical |
Possibly fewer steroid side-effects than conventional corticosteroid therapy |
Intravenous administration; labour intensive; risk of bladder malignancy and infertility |
Alopecia; infections; infertility; haemorrhagic cystitis; acne; hiccup |
B (2++) |
Intravenous immunoglobulin |
Possible adjuvant maintenance agent for recalcitrant PV failed on other regimens; could be considered in severe cases to induce remission while slower-acting drugs take effect |
Rapid action reported in some cases; no increased risk of opportunistic infection |
Intravenous administration; very expensive; labour intensive; theoretical risk of blood-borne virus infections |
During infusion, chills, tachycardia, hypertension, muscle pains, pyrexia, nausea and headache are common, self-limited and respond to slowing the infusion; anaphylaxis is rare (increased risk in IgA deficiency) |
D (3) |
Extracorporeal photopheresis |
May be considered in recalcitrant disease where conventional treatment has failed |
Can be performed via peripheral venous access |
Specialist equipment; trained staff; labour intensive; expensive; limited availability; limited data; ultraviolet protective sunglasses on the day of treatment; venous access can be a problem |
Symptoms of hypovolaemia during procedure |
D (3) |
Immunoadsorption |
Should be reserved for the treatment of patients resistant to or intolerant of other approaches and should be used in combination with treatment directed at suppressing new antibody formation |
Rational therapy aimed at rapidly decreasing pathogenic antibody levels; generally well tolerated |
Expensive; inconvenient; rebound antibody production |
Hypotension; anaphylaxis; sepsis |
D (3) |
Methotrexate |
Could be used as an adjuvant drug if others are poorly tolerated, contraindicated or ineffective |
Oral administration; inexpensive; dermatologists very familiar with it |
Slow onset |
Myelosuppression; hepatotoxicity; pneumonitis |
D (3) |
Oral cyclophosphamide |
Could be considered as an alternative to azathioprine and mycophenolate mofetil if secondary infertility is not a concern |
Inexpensive; oral administration |
Potential risk of haemorrhagic cystitis and carcinoma of bladder |
Neutropenia; alopecia; gastrointestinal disturbances; raised transaminases; thrombocytopenia; secondary infertility; nausea |
D (3) |
Plasma exchange and plasmapheresis |
Not recommended as routine; may be considered for difficult cases if combined with steroids and immunosuppressants |
Direct and immediate removal of IgG and therefore removal of PV antibodies |
Central venous access; specialist equipment; trained staff; limited availability; labour intensive; expensive; rebound production of PV antibodies after plasma exchange |
Septicaemia; fluid and electrolyte imbalance |
D (3), historical treatment |
Gold |
More commonly used as an adjuvant, enabling steroid dose reduction; an alternative to more established adjuvant drugs |
Inexpensive |
Intramuscular administration; slow onset; not commonly used |
Rashes; nephrotic syndrome; myelosuppression; hypersensitivity syndromes |
D (good practice point) (4) |
Pulsed intravenous corticosteroids |
Consider for remission induction in severe or recalcitrant disease, particularly if unresponsive to high oral doses |
Rapid onset; inexpensive |
Intravenous administration |
Mood changes; flushing |
Not recommended (1−) |
Ciclosporin |
|
|
Side-effects; expensive |
Hypertension; renal impairment; gastrointestinal disturbances; hypertrichosis; hypertrophic gingivitis |
Insufficient evidence (3) |
Chlorambucil |
Although it may be used in practice, further study is needed before recommendation |
Oral administration; inexpensive |
Minimal data |
Myelosuppression |
Insufficient evidence (1−) |
Dapsone |
Although it may be used in practice, further study is needed before recommendation |
Inexpensive |
Minimal data |
Haemolysis; methaemoglobinaemia; hypersensitivity reactions |
Insufficient evidence (2−) |
Sulfasalazine or pentoxifylline |
Although it may be used in practice, further study is needed before recommendation |
Oral administration; inexpensive |
Frequent dosing (two tablets twice daily) |
Gastric pain; nausea and headache |
Insufficient evidence (3) |
Tetracyclines and nicotinamide |
Tetracycline/nicotinamide could be considered as an adjuvant in milder PV |
Inexpensive |
Lots of tablets |
Flushing and headaches due to vasodilation with nicotinamide; gastrointestinal upset (tetracyclines); hyperpigmentation, particularly at sites of blistering (minocycline); discoloration of teeth (avoid tetracyclines in children and pregnant or lactating women) |