JAAD ONLINE CASE
LETTER
Cutaneous pseudolymphoma: A rare side effect of cyclosporine To the Editor: Cyclosporine was first licensed for use in psoriasis in 1997 and is an effective systemic treatment for this disease, especially when rapid remission is desired. The most commonly reported side effects are acute kidney injury, hyperlipidemia (especially hypertriglyceridemia), hypertension, gastrointestinal upset, and headaches.1 The majority of these side effects are related to dose and treatment duration and are reversible in patients treated with short courses, that is, treatment lasting less than 2 years. Here we highlight cutaneous pseudolymphoma as a rare side effect of treatment with cyclosporine. A 41-year-old Brazilian man with thick confluent plaque psoriasis (80% body surface area affected, Psoriasis Area and Severity Index 20, Dermatology Life Quality Index 25) and no other past medical history was commenced on cyclosporine. Previously he had a poor response to narrowband UVB phototherapy and flared after 2 treatments with PUVA. During the first 2 months on cyclosporine he developed a transient neutropenia, ankle edema, and night sweats. Chest radiograph and Mantoux test were normal. He developed blue-black dermal nodules on his lower back (Fig 1) 10 months into treatment with cyclosporine 4 mg/kg/day. Histopathologic evaluation showed a dermal infiltrate composed of lymphocytes and prominent plasma cells (Fig 2). Kappa and lambda stains done to investigate the plasma cell population showed a normal ratio, thus favoring a reactive diagnosis. Syphilis serology was negative, as were T-cell receptor gene rearrangement studies. The nodules increased in size and number over 4 weeks. The dose of cyclosporine was reduced and acitretin was added because of hypertension and rising creatinine. Within 4 days of stopping cyclosporine, the nodules reduced in number and size. Three months later they were fully resolved, and 27 months later there was no evidence of recurrence. The patient has been maintained on adalimumab 40 mg weekly with minimal psoriasis and no recurrence of the nodules after 2 years of tumor necrosis factor antagonist therapy. Cutaneous pseudolymphoma describes a heterogeneous group of benign reactive T-cell or B-cell lymphoproliferative processes of diverse causes that simulate cutaneous lymphoma clinically J AM ACAD DERMATOL
Fig 1. Cutaneous pseudolymphoma. Blue-black nodules on background of erythroderma.
Fig 2. Cutaneous pseudolymphoma. Monomorphic plasma cell infiltrate. (Hematoxylin-eosin stain. Original magnification: 3200.)
and histologically.2 It is unclear whether cutaneous pseudolymphoma may progress to lymphoma in that previously reported cases may represent initial histologic misdiagnosis.2 Even though most cases are idiopathic, cutaneous pseudolymphoma has also been described in association with tattoos, vaccinations, infections, and inflammatory dermatoses.3 Drug-induced cutaneous pseudolymphoma is most commonly reported with antiepileptic agents ( phenytoin, carbamazepine, lamotrigine, sodium valproate) but has also been described with tumor necrosis factor MARCH 2015 e85
J AM ACAD DERMATOL
e86 Letter
inhibitors, methotrexate, calcium channel blockers, and tamoxifen.4 In most cases the lesions resolved on cessation of the causative agent. There has been one previous report of cutaneous pseudolymphoma in a patient treated with cyclosporine for actinic reticuloid.5 In that case the tumor partly regressed when cyclosporine was stopped but radiotherapy was necessary for clearance. In our patient, the temporal relationship between the discontinuation of cyclosporine and the rapid resolution of nodules suggests an association with cyclosporine. Our patient is followed closely in the dermatology outpatient clinic. Catherine Foley, MB BCh, MRCPI,a Niamh Leonard, MB,b and Bairbre Wynne, MB BCh BAO LRCP&SI MRCPI a Department of Dermatologya and Department of Histopathology,b St James’s Hospital, Dublin, Ireland The case was presented at the Gross and Microscopic Symposium at the American Academy of Dermatology 71st Annual Meeting, Miami Beach, FL, March 1-5, 2013.
MARCH 2015
Funding sources: None. Conflicts of interest: None declared. Correspondence to: Dr Bairbre Wynne, MB BCh BAO LRCP&SI MRCPI, Department of Dermatology, St James’s Hospital, Dublin 8, Ireland E-mail: [email protected] REFERENCES 1. Ryan C, Amor KT, Menter A. The use of cyclosporine in dermatology: part II. J Am Acad Dermatol 2010;63:949-72. 2. Bergman R. Pseudolymphoma and cutaneous lymphoma: facts and controversies. Clin Dermatol 2010;28:568-74. 3. Cristaudo A, Forte G, Bocca B, Petrucci F, Muscardin L, Trento E, Di Carlo A. Permanent tattoos: evidence of pseudolymphoma in three patients and metal composition of the dyes. Eur J Dermatol 2012;22:776-80. 4. Imafuku S, Ito K, Nakayama J. Cutaneous pseudolymphoma induced by adalimumab and reproduced by infliximab in a patient with arthropathic psoriasis. Br J Dermatol 2012;166: 675-8. 5. Thestrup-Pedersen K, Zachariae C, Kaltoft K, Pallesen G, Søgaard H. Development of cutaneous pseudolymphoma following ciclosporin therapy of actinic reticuloid. Dermatologica 1988;166:376-81. http://dx.doi.org/10.1016/j.jaad.2014.09.008
LETTER
Cutaneous pseudolymphoma: A rare side effect of cyclosporine To the Editor: Cyclosporine was first licensed for use in psoriasis in 1997 and is an effective systemic treatment for this disease, especially when rapid remission is desired. The most commonly reported side effects are acute kidney injury, hyperlipidemia (especially hypertriglyceridemia), hypertension, gastrointestinal upset, and headaches.1 The majority of these side effects are related to dose and treatment duration and are reversible in patients treated with short courses, that is, treatment lasting less than 2 years. Here we highlight cutaneous pseudolymphoma as a rare side effect of treatment with cyclosporine. A 41-year-old Brazilian man with thick confluent plaque psoriasis (80% body surface area affected, Psoriasis Area and Severity Index 20, Dermatology Life Quality Index 25) and no other past medical history was commenced on cyclosporine. Previously he had a poor response to narrowband UVB phototherapy and flared after 2 treatments with PUVA. During the first 2 months on cyclosporine he developed a transient neutropenia, ankle edema, and night sweats. Chest radiograph and Mantoux test were normal. He developed blue-black dermal nodules on his lower back (Fig 1) 10 months into treatment with cyclosporine 4 mg/kg/day. Histopathologic evaluation showed a dermal infiltrate composed of lymphocytes and prominent plasma cells (Fig 2). Kappa and lambda stains done to investigate the plasma cell population showed a normal ratio, thus favoring a reactive diagnosis. Syphilis serology was negative, as were T-cell receptor gene rearrangement studies. The nodules increased in size and number over 4 weeks. The dose of cyclosporine was reduced and acitretin was added because of hypertension and rising creatinine. Within 4 days of stopping cyclosporine, the nodules reduced in number and size. Three months later they were fully resolved, and 27 months later there was no evidence of recurrence. The patient has been maintained on adalimumab 40 mg weekly with minimal psoriasis and no recurrence of the nodules after 2 years of tumor necrosis factor antagonist therapy. Cutaneous pseudolymphoma describes a heterogeneous group of benign reactive T-cell or B-cell lymphoproliferative processes of diverse causes that simulate cutaneous lymphoma clinically J AM ACAD DERMATOL
Fig 1. Cutaneous pseudolymphoma. Blue-black nodules on background of erythroderma.
Fig 2. Cutaneous pseudolymphoma. Monomorphic plasma cell infiltrate. (Hematoxylin-eosin stain. Original magnification: 3200.)
and histologically.2 It is unclear whether cutaneous pseudolymphoma may progress to lymphoma in that previously reported cases may represent initial histologic misdiagnosis.2 Even though most cases are idiopathic, cutaneous pseudolymphoma has also been described in association with tattoos, vaccinations, infections, and inflammatory dermatoses.3 Drug-induced cutaneous pseudolymphoma is most commonly reported with antiepileptic agents ( phenytoin, carbamazepine, lamotrigine, sodium valproate) but has also been described with tumor necrosis factor MARCH 2015 e85
J AM ACAD DERMATOL
e86 Letter
inhibitors, methotrexate, calcium channel blockers, and tamoxifen.4 In most cases the lesions resolved on cessation of the causative agent. There has been one previous report of cutaneous pseudolymphoma in a patient treated with cyclosporine for actinic reticuloid.5 In that case the tumor partly regressed when cyclosporine was stopped but radiotherapy was necessary for clearance. In our patient, the temporal relationship between the discontinuation of cyclosporine and the rapid resolution of nodules suggests an association with cyclosporine. Our patient is followed closely in the dermatology outpatient clinic. Catherine Foley, MB BCh, MRCPI,a Niamh Leonard, MB,b and Bairbre Wynne, MB BCh BAO LRCP&SI MRCPI a Department of Dermatologya and Department of Histopathology,b St James’s Hospital, Dublin, Ireland The case was presented at the Gross and Microscopic Symposium at the American Academy of Dermatology 71st Annual Meeting, Miami Beach, FL, March 1-5, 2013.
MARCH 2015
Funding sources: None. Conflicts of interest: None declared. Correspondence to: Dr Bairbre Wynne, MB BCh BAO LRCP&SI MRCPI, Department of Dermatology, St James’s Hospital, Dublin 8, Ireland E-mail: [email protected] REFERENCES 1. Ryan C, Amor KT, Menter A. The use of cyclosporine in dermatology: part II. J Am Acad Dermatol 2010;63:949-72. 2. Bergman R. Pseudolymphoma and cutaneous lymphoma: facts and controversies. Clin Dermatol 2010;28:568-74. 3. Cristaudo A, Forte G, Bocca B, Petrucci F, Muscardin L, Trento E, Di Carlo A. Permanent tattoos: evidence of pseudolymphoma in three patients and metal composition of the dyes. Eur J Dermatol 2012;22:776-80. 4. Imafuku S, Ito K, Nakayama J. Cutaneous pseudolymphoma induced by adalimumab and reproduced by infliximab in a patient with arthropathic psoriasis. Br J Dermatol 2012;166: 675-8. 5. Thestrup-Pedersen K, Zachariae C, Kaltoft K, Pallesen G, Søgaard H. Development of cutaneous pseudolymphoma following ciclosporin therapy of actinic reticuloid. Dermatologica 1988;166:376-81. http://dx.doi.org/10.1016/j.jaad.2014.09.008
