Dapsone induced haemolytic anaemia in patients treated for ocular cicatricial pemphigoid

Ocular cicatricial pemphigoid (OCP) is a systemic autoimmune disease of unknown aetiology. It causes a chronic, scarring conjunctivitis and frequently affects other mucous membranes. Definitive diagnosis is made by immunofluorescent staining of conjunctival tissue demonstrating IgG, IgM, and or IgA in the basement membrane.¹ Dapsone is an immunomodulating sulphonamide and has widely been used in the treatment of mild to moderate OCP.²,³,⁴ All patients treated with dapsone show varying degrees of haemolysis.⁵ Haemolytic anaemia, requiring withdrawal of therapy, has been shown to occur in approximately 10% of patients.²,⁵

The medical records of 12 patients treated with dapsone for ocular cicatricial disease were reviewed. Eleven of these patients were treated with dapsone as first line therapy and one as second line therapy; 11 patients had ocular cicatricial pemphigoid (OCP) and one had idiopathic cicatrising disease. There were an equal number of male and females in this group with a mean age of 72 years (range 55–89 years). The daily dose of dapsone was consistent at 50 mg twice daily taken orally. Mean follow up time while on dapsone therapy was 19 months with a range of 1–60 months.

Six (50%) patients had reticulocytosis including four (33%) with clinically significant haemolytic anaemia with a raised mean cell volume and a steady fall in haemoglobin from baseline. The development of the haemolytic anaemia was not dose dependent and all the patients had a diagnosis of OCP (table 1).

Table 1 Patients with haematological complications from dapsone.

Patient	Age (years)	Sex	Diagnosis	Dapsone dose		Complication
1	77	M	OCP	50 mg twice daily		Reticulocytosis (with normal Hb)
2	78	M	OCP	50 mg twice daily		Haemolytic anaemia*
3	67	M	OCP	50 mg twice daily		Reticulocytosis (with normal Hb)
4	60	F	OCP	50 mg twice daily		Haemolytic anaemia*
5	89	F	OCP	50 mg twice daily		Haemolytic anaemia*
6	85	F	OCP	50 mg twice daily		Haemolytic anaemia*

OCP, ocular cicatricial pemphigoid, Hb, haemoglobin, *dapsone withdrawn.

Our cohort of patients had a much higher rate of haemolytic anaemia than previously published reports.²,⁵ Although our study sample is small, the proportion of patients with haemolytic anameia is striking. Patients who are glucose‐6‐phosphate hydrogenase (G6PD) deficient are known to be more at risk of developing haemolytic anaemia.⁴ We do not routinely check for this rare deficiency in our department. Clinically significant dapsone induced haemolytic anaemia may occur more frequently than previously expected and clinicians should be acutely aware of any downward trend in haemoglobin from baseline. We no longer use dapsone as a first line agent in the management of OCP.