Erythrodermic Psoriasis after Rituximab Treatment in a Patient with Autoimmune Hemolytic Anemia.

Sir,

A 57-year-old Caucasian man was diagnosed with autoimmune hemolytic anemia (AIHA) in December 2017. He had been treated, for his AIHA, with a gradually reduced course of oral methylprednisolone starting from 32 mg once daily tapered to 4 mg once daily within 12 months, valaciclovir 500 mg once daily, filicine 5 mg once daily, trimethoprim/sulfamethoxazole (800 + 160 mg) once daily, oral fluconazole 200 mg once daily, and oral dimethindene 10 mg once daily. His past medical history included essential hypertension and type 2 diabetes mellitus. He was on treatment with oral metformin 500 mg three times a day, insulin glargine 20–30 units daily and eprosartan, an angiotensin II receptor antagonist, 600 mg once daily. In October 2018, after failing the aforementioned medications, he was started on rituximab originator (MabThera) 750 mg intravenously once weekly for 4 consecutive weeks. Seven weeks after the first infusion of rituximab, he developed widespread erythrodermic psoriasis affecting his trunk, limbs, neck, and face. At that time, the patient was referred to our dermatology department for review. On examination, he had widespread erythematous psoriatic plaques on the trunk, upper and lower limbs, face, and neck [Figure 1] clinically more in keeping with erythrodermic psoriasis. He reported that in the last one year, he had developed multiple scaly erythematous papules and plaques on his trunk, upper and lower limbs that severely deteriorated in the last 7 days. Upon review of his notes, there was a history of mild erythematous plaques on elbows in the last 6 years that flared up every summer but he had not previously visited a dermatologist for this. He also reported that his father had similar scaly erythematous plaques on his elbows. Acute infections in the last 6 months were not reported. A skin biopsy specimen was consistent with psoriasis [Figures 2 and 3]. He was initially started on treatment with topical emollients, soap substitutes, and oral prednisolone 20 mg once daily with gradual tapering over an eight-week period for his erythrodermic psoriasis. Two weeks after having started oral prednisolone, he was administered also oral methotrexate 10 mg once weekly that was increased after 2 weeks to oral methotrexate 12.5 mg once weekly achieving almost complete remission of psoriasis within 4 weeks. No further rituximab cycles were given. The patient is receiving ongoing follow-up with the hematology department.

Figure 1

Widespread psoriatic plaques on the trunk and limbs

Figure 2

Histology showed psoriasiform epidermal hyperplasia with intraepidermal collection of neutrophils and mild lymphocytic infiltrate in papillary dermis (hematoxylin-eosin stain; magnification: ×4)

Figure 3

The epidermis shows thickening (acanthosis) with regular rete ridges and parakeratosis. Papillary dermis shows a chronic inflammatory infiltrate (hematoxylin-eosin stain; magnification: ×20)

The close temporal association between the rituximab infusions and the onset of erythrodermic psoriasis together with the almost complete recovery after 8 weeks pointed out a drug-related adverse event.

Between 2007 and 2016, 16 cases of new-onset psoriasis and 6 cases of exacerbation of psoriasis were reported in patients taking rituximab.

Fifteen case reports have described the development or exacerbation of chronic plaque psoriasis secondary to rituximab[1234] and one multicenter analysis reviewed 1927 patients taking rituximab for rheumatoid arthritis [Table 1].[5] Two patients developed psoriasis and five patients had an exacerbation of preexisting psoriasis.[5]

Table 1

Summary of rituximab (RTX) induced or exacerbation of psoriasis cases

Author	Year	Country	Age	Sex	Disease	Rheumatoid factor/anticyclic citrullinated peptide	Past medical history of psoriasis	Lesion sites
Dass S.	2007	Leeds, United Kingdom	17	Female	Rheumatoid arthritis (RA)	–/–	No	Scalp, onycholysis
Dass S.	2007	Leeds, United Kingdom	52	Female	Rheumatoid arthritis	+/+	No	Knees, extensor surfaces of thighs
Dass S.	2007	Leeds, United Kingdom	26	Female	Systemic lupus erythematosus (SLE)	–/–	No	Widespread, elbows, arms, thighs, trunk, onycho lysis
Mielke F.	2008	Berlin, Germany	66	Female	NHL	Not available (N/A)	No	Scalp, extensor surfaces
Markatseli T.A.	2009	Ioannina, Greece	55	Female	Rheumatoid arthritis	+/+	No	Arms, thighs
Brunasso A.	2011	Gratz, Austria and Genoa, Italy	45	Female	Rheumatoid arthritis	+/+	No	Plantar psoriasis
Guidelli G.M.	2012	Siena, Italy	69	Female	Rheumatoid arthritis	+/+	No	Diffuse psoriatic lesions, trunk and arms
Hardcastle S.	2012	Swindon, United Kingdom	49	Female	Rheumatoid arthritis	–/–	Guttate psoriasis in her teens	Acral psoriasis, ankles and heels
Thomas L.	2012	Creteil, France	66	Female	Rheumatoid arthritis	–/–	No	Not available (N/A)
Thomas L.	2012	Creteil, France	79	Female	Rheumatoid arthritis	–/–	No	Elbows
Thomas L.	2012	Creteil, France	41	Female	Rheumatoid arthritis	N/A	Yes, exacerbation of psoriasis	Scalp
Thomas L.	2012	Creteil, France	73	Female	Rheumatoid arthritis	Not available (N/A)	Yes, exacerbation of psoriasis	Palmoplantar pustular psoriasis
Thomas L.	2012	Creteil, France	58	Female	Rheumatoid arthritis	Not available (N/A)	Yes, exacerbation of psoriasis	Legs
Thomas L.	2012	Creteil, France	60	Female	Rheumatoid arthritis	Not available (N/A)	Yes, exacerbation of psoriasis	Palmoplantar pustular psoriasis and elbows
Thomas L.	2012	Creteil, France	67	Female	Rheumatoid arthritis	Not available (N/A)	Yes, exacerbation of psoriasis	Legs
Toussirot E.	2013	Besancon, France	44	Female	Rheumatoid arthritis	–/–	No	Scalp
Ming Yee Mok M.	2013	Hong Kong and China	51	Male	Idiopathic membranous nephropahty (IMN)	Not available (N/A)	No	Pustular psoriasis trunk and limbs
Ozen G.	2013	Istanbul, Turkey	50	Female	Rheumatoid arthritis	+/–	No	Extremities, guttate
Jayasekera P.	2014	Liverpool, United Kingdom	80	Female	Rheumatoid arthritis	Not available (N/A)	No	Right plantar pustulosis
Fiorillo L.	2014	Alberta and Vancouver, Canada	16-months old	Male	Idiopathic thrombocytopenic purpura (ITP)	Not available (N/A)	No	Legs, scalp, back, and arms
Venables Z.C.	2015	Northampton, United Kingdom	53	Female	NHL	Not available (N/A)	No	Palmoplantar
Kim D.W.	2016	Chonbuk, South Korea	6	Male	NHL	Not available (N/A)	No	Shoulder, chest, abdomen and back and whole scalp
Koumaki D.	2019	Heraklion, Greece	57	Male	Autoimmune hemolytic anemia (AIHA)	–/–	Yes	Erythrodermic, widespread, trunk, limbs, neck
Author	Diagnosis		Psoriasis onset after rituximab	Total rituximab cycles	Rituximab originator/r biosimilar use	Therapy	Rituximab continuation	Prognosis of psoriasis
Dass S.	Clinical, dermatology review		Six months after first cycle	1	Rituximab originator	Topical and systemic	Not available	Active
Dass S.	Clinical, dermatology review		4 months after second course	2	Rituximab originator	Topical steroid	Not available	Resolution after 3 months of treatment
Dass S.	Clinical, dermatology review		4 months after second course	1	Rituximab originator	Topical steroid	Not available	Partial remission
Mielke F.	Clinical, rheumatology review		6–8 weeks after first cycle	8	Rituximab originator	Topical steroids, MTX and oral steroid	Yes	Resolution
Markatseli T.A.	Clinical and biopsy		10 days after second course	2	Rituximab originator	Topical steroids	Not available	Not available
Brunasso A.	Clinical and biopsy		4 months after first dose of rituximab	1	Rituximab originator	intramuscular methylprednisolone topical steroids, MTX	No	Complete remission
Guidelli G.M.	Clinical and biopsy		3 months after second course	1	Rituximab originator	Topical steroid	Not available	Complete resolution
Hardcastle S.	Clinical, dermatology review		10 weeks after first cycle	1	Rituximab originator	Topical treatment with steroid, salicyclic acid and coal tar	Not available	Resolution
Thomas L.	Clinical rheumatology review		6 months after first cycle	2	Rituximab originator	Nil	Yes	Resolution
Thomas L.	Patient reported developing psoriasis, no medical input, doubtful diagnosis		2 weeks after second course	3	Rituximab originator	Nil	Yes	Full resolution
Thomas L.	Clinical, dermatology review		4 months after the second infusion of the third rituximab course	3	Rituximab originator	Not available	Not available	Improvement within 3 months
Thomas L.	Not available (N/A)		4 months after the first course	2	Rituximab originator	Topical treatment	Not available	Improvement
Thomas L.	Not available (N/A)		4 months after the second infusion of the first rituximab course	3	Rituximab originator	Topical treatment	Not available	Improvement
Thomas L.	Not available (N/A)		7 months after the second infusion of the first rituximab course	1	Rituximab originator	Nil	Not available	Cleared spontaneously
Thomas L.	Not available (N/A)		8 months after the second infusion of the second rituximab course	3	Rituximab originator	Topical treatment	Yes	Improvement
Toussirot E.	Clinical, dermatology review		Five months after the first RTX administration	1	Rituximab originator	N/A	Yes	Stable
Ming Yee Mok M.	Not available (N/A)		Three months after of completion of RTX treatment	2	Rituximab originator	Topical treatment	No	Gradual improvement
Ozen G.	Clinical dermatology review and biopsy		25 months after first infusion	3	Rituximab originator	Topical treatment	Yes	Deterioration
Jayasekera P.	Clinical, dermatology review		2 years after starting rituximab	N/A	Rituximab originator	Topical steroid treatment	No	Cleared completely
Fiorillo L.	Clinical dermatology review and biopsy		7 weeks after starting RTX	6	Rituximab originator	Topical steroid, MTX but discontinued due to intolerance	Yes	Cleared after 1 year
Venables Z.C.	Clinical dermatology review		2–3 weeks after each cycle RCVP, she developed pustules on her soles and 2 weeks after the initial infusion of RTX she developed severe palmoplantar pustulosis	6	Rituximab originator	Potent topical steroids	No	Complete remission, no further relapse
Kim D.W.	Clinical dermatology review and biopsy		3 months after starting RTX	3	Rituximab originator	Topical treatment	Yes	Complete remission
Koumaki D.	Clinical dermatology review and biopsy		7 weeks after first infusion	2	Rituximab Originator	Topical and systemic treatment, oral prednisolone and MTX	No	Partial improvement

RTX=Rituximab, RF=Rheumatoid factor, anti-CCP=Anticyclic citrullinated peptide, PMH=Past medical history, F=Female, M=Male, RA=Rheumatoid arthritis, NHL=Non-Hodgkin lymphoma, IMN=Idiopathic thrombocytopenic purpura, DM=Dermatomyositis, SLE=Systemic lupus erythematosus, MTX=Methotrexate, N/A=Not available, RCVP=Intravenous rituximab, cyclophosphamide, and vincristine with oral prednisolone, AIHA=Autoimmune hemolytic anemia

To the best of our knowledge here, we have reported a rare case of erythrodermic psoriasis after rituximab treatment.

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Conflicts of interest

There are no conflicts of interest.