psoriasis is a common , chronic , disfiguring , relapsing , inflammatory , and proliferative condition of the skin .
long - term treatment of moderate - to - severe psoriasis is challenging and often requires a combination , rotational or sequential therapy , with two or more systemic agents .
although it had been avoided earlier , combination therapy with methotrexate and cyclosporine is being increasingly found to be safe and useful in the management of psoriasis .
we report here the case of a 57-year - old patient with unstable psoriasis , who developed unexpected methotrexate toxicity and cyclosporine - induced thrombocytosis in a span of two weeks of being given both drugs sequentially .
we present this case to highlight the as - yet - unknown toxicities and interactions encountered with the administration of methotrexate and cyclosporine in the treatment of psoriasis .
a 57-year - old male , who was known to be suffering from psoriasis vulgaris for the past 10 years , presented to us with features of unstable psoriasis for a duration of two weeks . he had been previously treated for multiple exacerbations with methotrexate ( cumulative dose - 2285 mg ) , cyclosporine , and topical steroids , on separate instances .
he was a known diabetic for the past 10 years , on regular treatment with tablet metformin 500 mg twice a day .
his baseline complete blood count showed leukocytosis ( leucocyte count - 18,300 cells / mm ; platelet count- 5  10/mm ) and the liver function tests were within normal limits . in view of the suspicion of unstable psoriasis , inj .
after 24 hours , he developed multiple pustules over the nape of the neck and multiple oral erosions , resulting in severe odynophagia , with the existing lesions becoming more erythematous [ figure 1 ] .
the hemogram showed a fall in the leukocyte counts ( 7,700 cells / mm ) .
improvement in his blood count was also noted , as they returned to normal in four days ( leucocyte count - 9,700 cells / mm ; platelet count - 4.11  10/mm ) .
the causality assessment , done using the naranjo algorithm , revealed a probable adverse drug reaction .
mild erythema and hyperpigmentation of plaques three days after starting methotrexate and folinic acid following this , the patient was started on cyclosporine 100 mg , twice a day , to control the unstable psoriasis .
one week after administration of cyclosporine , it was noticed that the platelet count increased three times from the baseline values ( 9.0  10/mm ) when tested , on multiple occasions .
the platelet count dropped to a high normal value ( 5  10/mm ) four days after withdrawing the drug , thus confirming our suspicion .
the naranjo scale scoring was 7 , which again implied a probable adverse drug reaction .
the patient was then started on acitretin 50 mg once a day and was discharged after resolution of the lesions [ figure 2 ] .
methotrexate and cyclosporine are considered to be the foremost treatment options of moderate - to - severe psoriasis . as both carry possible side effects and complications ,
factors predictive of methotrexate toxicity in patients with rheumatoid arthritis include absence of folate supplementation , high body mass index , prior gastrointestinal events , lower age group , female sex , renal impairment , change in dose , drug interactions , and infection .
it remains unexplained as to why this patient , who had received methotrexate for many years , suddenly developed methotrexate toxicity after a relatively low dose .
he was given a low dose of parenteral methotrexate , as he developed unstable psoriasis while on a low dose of oral methotrexate .
the role of change of route of administration in causing methotrexate toxicity remains to be studied .
an alternative explanation for thrombocytosis in our patient could be a reactive thrombocytosis set off by methotrexate toxicity or by the disease itself .
however , the normal platelet count after withdrawal of cyclosporine is more suggestive of the former .
reactive thrombocytosis is the exaggerated physiological response to a primary stimulus and is also known to accompany chronic inflammatory diseases like psoriasis .
yasumoto et al . also reported reactive thrombocytosis in two patients with psoriasis , with associated raised il-6 ( interleukin-6 ) levels , thus supporting the theory that thrombocytosis could be caused by the disease per se . however
, the fact that il-6 also has a role in the pathogenesis of psoriasis as t memory / effector cells that are chronically activated and poorly suppressed by regulatory t cells must be remembered .
il-6 signals through stat3 and allows the escape of t memory / effector cells from t regulator - mediated suppression in a murine system .
cyclosporine can induce il-1 expression in circulatory leukocytes and this may be sufficient to induce il-6 production in some tissues .
this is a plausible explanation to the increase in platelet counts during cyclosporine therapy in our patient .
the role of platelets in the inflammatory process is increasingly being recognized , in addition to their function in hemostasis and thrombosis .
hence , the effect of the inflammatory process of unstable psoriasis on the platelet counts or vice versa is also an interesting postulate in our case ; the temporal course of events do not , however , suggest a correlation .
we found it curious that our patient developed cyclosporine - induced - thrombocytosis a week after he recovered from unexplained methotrexate toxicity .
there are no reports on similar hematological manifestations because of the potential interactions between methotrexate and cyclosporine when administered concurrently or sequentially .
however , a study on the cytogenetic effect of methotrexate on human cells in vivo showed that methotrexate had a chromosome - breaking effect on human bone marrow cells .
recent studies have highlighted that methotrexate and cyclosporine can be co - administered in patients with difficult - to - treat psoriasis .
however , this case shows that there is still a need for caution , as late sequelae of long - term administration of the drugs are still unknown .
we present this case to highlight that unknown long - term toxicities and unexplored interactions between systemic agents used for psoriasis still remain a chink in our therapeutic armamentarium for this common disease .
this defect can be repaired by well - planned cohort studies and meticulous documentation of records of patients .
 psoriasis is a common , chronic , disfiguring , inflammatory , and proliferative condition of the skin . 
 it manifests with varying degrees of severity and can be treated with various immune modulators . 
 this is a case report of a 57-year - old male patient of psoriasis on long - term oral methotrexate , who developed methotrexate toxicity when given an injection of methotrexate for unstable psoriasis . 
 after recovery , the patient was started on cyclosporine 100 mg twice a day . after a week , he developed thrombocytosis , which reverted a week after cyclosporine was stopped . 
 the patient is currently being managed with acitretin . 
 the aim of this case report is to emphasize the various unpredictable adverse reactions encountered during treatment of psoriasis , especially when a combination or sequential treatment is used . 
 there is a need for caution , as late sequelae of long - term administration of the systemic agents used in the treatment of psoriasis are still unknown . 