Sir,
Gemcitabine is a fluorine-substituted deoxycytidine analog used for different types
of malignancies such as locally advanced or metastatic adenocarcinoma of pancreas,
nonsmall cell lung cancer, breast cancer, epithelial ovarian cancer, and pancreatic
cancer. We report a case of 64-year-old male, diagnosed case of adenocarcinoma head
of pancreas, who presented to our outpatient department with acute onset of painful
confluent erythematous swelling of both lower extremities extending from toes to knees
[Figure 1] 2 days after receiving first cycle of gemcitabine-based chemotherapy. There was
no history of recent trauma to his legs, travel in recent past, insect or tick bite,
pruritus, previous similar episodes, chronic edema of lower extremities, fever with
chills, and rigor which can suggest thrombotic and/or infectious cause. On examination,
the patient was afebrile, local warmth and mild tenderness were present over erythematous
lower extremity swellings, and dorsalis pedis pulsations were felt equally in both
lower limbs. We considered infectious cellulitis, lymphedema, deep vein thrombosis
(DVT), radiation recall dermatitis, and gemcitabine-induced pseudocellulitis as differential
diagnosis of present clinical condition. Infectious cellulitis was excluded as systemic
manifestations were absent and counts were within normal limits. Doppler ultrasound
of venous system of both lower extremities was negative for DVT. Lymph edema was excluded
as there was no history of swelling in the past and present swelling was sudden in
onset. Since he had not received radiotherapy, radiation recall dermatitis was ruled
out. Consequently, diagnosis of gemcitabine-induced pseudocellulitis was made.
Figure 1: Patient with confluent erythema and edema on bilateral lower extremitis
Although areas of impaired lymphatic drainage lead to drug permeation into interstitial
fluid, drug accumulating in subcutaneous tissue and inadequate drug inactivation in
the subcutaneous tissue leading to nonnecrotizing inflammation of dermis and hypodermis
from a noninfectious etiology has been hypothesized as pathophysiology behind gemcitabine-related
pseudocellulitis.[1] However, it can develop even in the absence of pre-existing lymphedema in that specific
area. These reactions usually occur within 12–24 h following gemcitabine exposure,[2] and bilateral lower extremity symptoms are seen. It is a self-limiting condition
with most cases showing full resolution within 48 h to 1 week.[2] Conservative management was planned and the patient was advised bed rest and nonsteroidal
anti-inflammatory drugs. Other treatment options such as diphenhydramine[2] and 0.1% triamcinolone acetonide cream under occlusion and compression stockings[3] have been used for symptomatic management of this toxic effect of gemcitabine. No
further investigations including biopsy specimen for histopathological examination
and tissue culture were done as part of diagnostic workup as done earlier.[3] Antibiotics including oral cephalosporins, clindamycin, and even intravenous vancomycin
were not administered as the patient did not manifest any clinical feature of infection
like fever or raised total leukocyte count as done in previous reported cases.[3] The swelling gradually subsided over the next 3 days and the patient was discharged
in stable condition. Later, when the patient was followed up in outpatient clinic,
pain and swelling had subsided, and there were no further complaints. Thus, we propose
that triad of temporal relationship between administration of gemcitabine and appearance
of lesions, absence of fever, normal total leukocyte is sufficient for diagnosis of
pseudocellulitis. Knowledge, awareness, and recognition by keeping high suspicion
of this adverse effect will help clinicians to make a correct diagnosis and prevent
unwarranted diagnostic tests. Conservative management but not the withdrawal of gemcitabine-based
chemotherapy is only required rather than administration of antibiotics.
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