Home / Case Study / Chemotherapy Induced Subacute Cutaneous Lupus Erythematosus
70 yrs old male patient presented at the gastro clinic with pain abdomen, loss of appetite, dyspepsia and weight loss for last 3 months. On clinical examination, he was haemodynamically stable, afebrile and his abdomen was distended with enlarged liver and periumbilical tenderness was present. Patient was advised for certain investigations. Haematological and biochemical parameters were within normal limits but hyponatremia was present.
USG whole abdomen revealed fatty liver with cholesterosis of gall bladder. Upper GI endoscopy showed grade 2 oesophageal varices and colonoscopy revealed small colonic polyp. CECT whole abdomen documented contrast enhanced lesion in distal body and tail of pancreas with invasion of adjacent stomach and splenic artery along with multiple hepatic lesions. CA19.9 was high (1233).
USG guided fine needle aspiration cytology (FNAC) from hepatic lesion confirmed metastatic cancer from pancreatic primary. Patient is a known diabetic and hypertensive on regular medications. Thereafter, patient was referred to oncology department and planned for chemotherapy with gemcitabine and NAB-paclitaxel based protocol (day 1 and day 8, every 3 weekly schedule). Chemotherapy was to be delivered under day-care services.
Patient was admitted for 1st cycle day 1 chemotherapy. His hyponatremia persisted (122). Sodium correction was done with (0.9%) normal saline and thereafter chemotherapy was initiated. During 2nd cycle of chemotherapy, hyponatremia resolved but patient complained of pain abdomen and liver transaminases were raised. Patient showed improvement in liver functions and pain abdomen resolved with supportive management only.
Four days post 3rd cycle day 1 chemotherapy patient developed cutaneous erythematous rash only in both malar regions. Rash was non photosensitive, non scaly and diffuse simulating malar flush. No rash was observed in any other parts of the body. After steroids and anti- histaminics rash faded after 2 days. Autoantibodies were tested (ANA, Anti dsDNA, SSA) and all were unremarkable.
Cutaneous lupus includes several lupus like syndromes that can be idiopathic, paraneoplastic or drug induced that develop with medications exposure and resolve after the offending medications are stopped. DILE (Drug Induced Lupus Erythematosus) presents With unique cutaneous distribution and autoantibodies in absence of systemic features. Skin lesions of DILE are generally annular-polycyclic or papulosquamous in character and involve symmetric regions.
The complex underlying mechanisms include UV light induced apoptosis which is associated with local inflammation and cytokine release. Histopathologically these lesions demonstrate interface dermatitis with vacuolar degeneration of basal keratinocytes and dermal mucinosis. This syndrome is characteristically associated with high titres of autoantibodies like anti-SSA. This patient's skin biopsy could not be done as rash resolved very fast and patient was unwilling for such procedure. Autoantibodies ANA, Anti dsDNA, SSA were non reactive.
Taxanes are highly lipophilic molecules requiring addition of biological solvents as vehicles, The original formulation of paclitaxel was emulsified using poly-ethoxylated castor oil (cremaphor). a vehicle known to possess the pharmacological properties that cause adverse effects. NAB-paclitaxel is a new generation solvent free formulation of paclitaxel that utilises albumin binding to increase the bioavialability of paclitaxel molecule. This case study is highly suggestive of association between DILE and NAB-paclitaxel. Further, paclitaxel induced DILE syndrome are not solely caused by the CREMAPHOR used in the original formulation of paclitaxel.
Currently there is no standard diagnostic criteria for DILE. It has been defined as a lupus like syndrome related to the drug exposure which resolves after discontinuation of the offending drug. A number of drugs have been associated with DILE like hydralazine, procainamide, isoniazid, minocycline, thiazides, calcium channel blockers, ACE inhibitors, terbinafine. anti-dyslipidemic agents and various chemotherapeutic drugs.
This case discussion is an effort to create awareness to link solvent free NAB-paclitaxel with DILE and it suggests that it is the paclitaxel molecule that was responsible for the reaction rather than the solvent. Urgent initiation of steroids resolved DILE in this particular patient. There-after chemotherapy was continued without any further such adverse event.
Diagnosis & management of DILE is usually very simple if the offending drug is identified as a single agent. However, if multiple drug combinations are used then this becomes quite challenging. In this case discussion paclitaxel in its novel formulation (NAB - paclitaxel) was clearly the offending agent. But continuous use even after the adverse event fortunately did not have any further recurrence of such episode.
