Peripheral bands in the setting of drug hypersensitivity syndrome
Authors: Jusleen Ahluwalia, Lisa Arkin, Markus Boos, Michelle Dunn, James Treat
Journal: Journal of the American Academy of Dermatology (2014)

To the Editor: Immature neutrophils in the peripheral circulation (bandemia) are an infrequently reported finding in drug hypersensitivity syndrome (DHS).1Brown T.S. Appel J.E. Kasteler J.S. Callen J.P. Hypersensitivity reaction in a child due to lamotrigine.Pediatr Dermatol. 1999; 16: 46-49Crossref PubMed Scopus (38) Google Scholar, 2Tichy E. Lam S. Militano U. Bessmertny O. A case of severe thrombocytopenia and antiepileptic hypersensitivity syndrome.J Pediatr Pharmacol Ther. 2003; 8: 29-33PubMed Google Scholar, 3Ben m'rad M. Leclerc-Mercier S. Blanche P. Franck N. Rozenberg F. Fulla Y. et al.Drug-induced hypersensitivity syndrome: clinical and biologic disease patterns in 24 patients.Medicine (Baltimore). 2009; 88: 131-140Crossref PubMed Scopus (143) Google Scholar We report a case of DHS with bandemia that resolved after withdrawal of the offending medication and initiation of prednisolone.A previously healthy, school-aged girl was admitted to the hospital with a 2-day history of fever, facial edema, cervical lymphadenopathy, and a morbilliform eruption that started on the face and progressed caudally. The rash and fever developed after 6 days of trimethoprim-sulfamethoxazole (TMP-SMX) therapy for an uncomplicated urinary tract infection. She denied ocular pain, dysphagia, odynophagia, dysuria, and painful skin. Physical examination revealed an ill-appearing African American child with a temperature of 39.9°C, mild tachycardia, and tachypnea. A blanching morbilliform eruption was noted on her face, trunk, and extremities with significant facial edema and subcentimeter, nontender cervical lymphadenopathy. Mucosal surfaces were spared. Laboratory values are listed in Table I. Blood culture revealed negative findings, as did repeated urinalysis and urine culture. Human herpesvirus-6 quantitative polymerase chain reaction was positive at 300 copies/μL. Epstein-Barr virus serologies showed no evidence of current or previous infection.Table IKey laboratory values on admissionLaboratory component (normal value)Values on admissionValues 1 d after discontinuation of 16-d corticosteroid taperValues after a total 31 d of corticosteroid treatmentWhite blood cell count (4.27-11.40 × 103/μL)4.98.111.6Bands (0%)16N/AN/AEosinophils (0.0%-4.0%)2.00.01.0Atypical lymphocytes (2%-3%)8.7N/AN/APlatelets (199-367 × 103/μL)138639215Hemoglobin (11.5-15.5 g/dL)10.611.912.9Urea nitrogen (5-17 mg/dL)71515Creatinine (0.1-0.5 mg/dL)0.80.50.60Alkaline phosphatase (175-420 U/L)111174151Alanine aminotransferase (10-35 U/L)4419442Aspartate aminotransferase (15-40 U/L)6729718Gamma-glutamyltransferase (11-21 U/L)253017C-reactive protein (0.0-0.9 mg/dL)8.1N/AN/AN/A, Not available. Open table in a new tab Although the patient's eosinophils were within normal reference range upon admission, the constellation of clinical and laboratory findings (morbilliform eruption with facial edema, fever, elevated liver enzymes and creatinine, and atypical lymphocytosis after administration of TMP-SMX) was suggestive of DHS. TMP-SMX was immediately discontinued, and prednisolone (1 mg/kg/d) was initiated, in addition to acetaminophen and maintenance intravenous fluids. After 1 day of therapy, her eruption had improved considerably, with normalization of her vital signs. Her repeated complete blood cell count on hospital day 2 demonstrated reduction of peripheral bands to 3%, normalization of serum creatinine, and improvement in liver function test results. Within 1 day of discontinuing the 16-day taper of prednisolone, however, her rash and fever recurred, and laboratory evaluation revealed elevated liver enzymes (Table I). Prednisolone (1 mg/kg/d) was reinitiated with subsequent normalization of laboratory values (Table I). The prednisolone was tapered after an additional 3 weeks of therapy with no evidence of recurrence.Although the presence of bandemia is frequently seen in systemic infection as a result of bone-marrow activation, it is rarely reported in DHS.1Brown T.S. Appel J.E. Kasteler J.S. Callen J.P. Hypersensitivity reaction in a child due to lamotrigine.Pediatr Dermatol. 1999; 16: 46-49Crossref PubMed Scopus (38) Google Scholar, 2Tichy E. Lam S. Militano U. Bessmertny O. A case of severe thrombocytopenia and antiepileptic hypersensitivity syndrome.J Pediatr Pharmacol Ther. 2003; 8: 29-33PubMed Google Scholar, 3Ben m'rad M. Leclerc-Mercier S. Blanche P. Franck N. Rozenberg F. Fulla Y. et al.Drug-induced hypersensitivity syndrome: clinical and biologic disease patterns in 24 patients.Medicine (Baltimore). 2009; 88: 131-140Crossref PubMed Scopus (143) Google Scholar Our patient's rapid resolution with discontinuation of TMP-SMX and initiation of prednisolone strongly suggests that the bandemia was caused by DHS rather than infection.Various mechanisms causing blood dyscrasias in DHS include cytotoxic antibody-mediated destruction, reversible inhibition of stem cell activity, cessation of myeloid maturation, and induction of cytokine-activated macrophages leading to the development of hemophagocytosis syndrome.3Ben m'rad M. Leclerc-Mercier S. Blanche P. Franck N. Rozenberg F. Fulla Y. et al.Drug-induced hypersensitivity syndrome: clinical and biologic disease patterns in 24 patients.Medicine (Baltimore). 2009; 88: 131-140Crossref PubMed Scopus (143) Google Scholar, 4Lambotte O. Costedoat-Chalumeau N. Amoura Z. Piette J.C. Cacoub P. Drug-induced hemophagocytosis.Am J Med. 2002; 112: 592-593Abstract Full Text Full Text PDF PubMed Scopus (41) Google Scholar The complex inflammatory response and the resultant cytokine storm, notably tumor necrosis factor-alfa among others, can stimulate the bone marrow to release immature neutrophils.5Criado P.R. Criado R.F. Avancini Jde M. Santi C.G. Drug reaction with eosinophilia and systemic symptoms (DRESS)/drug-induced hypersensitivity syndrome (DIHS): a review of current concepts.An Bras Dermatol. 2012; 87: 435-449Crossref PubMed Scopus (123) Google ScholarRecognition of the constellation of clinical findings suggestive of DHS is vital particularly when bandemia is present, as failure to stop the offending medication can lead to exacerbation of the underlying hypersensitivity, with resultant multisystem organ failure. Bands are most commonly associated with infection, but this report confirms that peripheral bands can also be associated with DHS. To the Editor: Immature neutrophils in the peripheral circulation (bandemia) are an infrequently reported finding in drug hypersensitivity syndrome (DHS).1Brown T.S. Appel J.E. Kasteler J.S. Callen J.P. Hypersensitivity reaction in a child due to lamotrigine.Pediatr Dermatol. 1999; 16: 46-49Crossref PubMed Scopus (38) Google Scholar, 2Tichy E. Lam S. Militano U. Bessmertny O. A case of severe thrombocytopenia and antiepileptic hypersensitivity syndrome.J Pediatr Pharmacol Ther. 2003; 8: 29-33PubMed Google Scholar, 3Ben m'rad M. Leclerc-Mercier S. Blanche P. Franck N. Rozenberg F. Fulla Y. et al.Drug-induced hypersensitivity syndrome: clinical and biologic disease patterns in 24 patients.Medicine (Baltimore). 2009; 88: 131-140Crossref PubMed Scopus (143) Google Scholar We report a case of DHS with bandemia that resolved after withdrawal of the offending medication and initiation of prednisolone. A previously healthy, school-aged girl was admitted to the hospital with a 2-day history of fever, facial edema, cervical lymphadenopathy, and a morbilliform eruption that started on the face and progressed caudally. The rash and fever developed after 6 days of trimethoprim-sulfamethoxazole (TMP-SMX) therapy for an uncomplicated urinary tract infection. She denied ocular pain, dysphagia, odynophagia, dysuria, and painful skin. Physical examination revealed an ill-appearing African American child with a temperature of 39.9°C, mild tachycardia, and tachypnea. A blanching morbilliform eruption was noted on her face, trunk, and extremities with significant facial edema and subcentimeter, nontender cervical lymphadenopathy. Mucosal surfaces were spared. Laboratory values are listed in Table I. Blood culture revealed negative findings, as did repeated urinalysis and urine culture. Human herpesvirus-6 quantitative polymerase chain reaction was positive at 300 copies/μL. Epstein-Barr virus serologies showed no evidence of current or previous infection. N/A, Not available. Although the patient's eosinophils were within normal reference range upon admission, the constellation of clinical and laboratory findings (morbilliform eruption with facial edema, fever, elevated liver enzymes and creatinine, and atypical lymphocytosis after administration of TMP-SMX) was suggestive of DHS. TMP-SMX was immediately discontinued, and prednisolone (1 mg/kg/d) was initiated, in addition to acetaminophen and maintenance intravenous fluids. After 1 day of therapy, her eruption had improved considerably, with normalization of her vital signs. Her repeated complete blood cell count on hospital day 2 demonstrated reduction of peripheral bands to 3%, normalization of serum creatinine, and improvement in liver function test results. Within 1 day of discontinuing the 16-day taper of prednisolone, however, her rash and fever recurred, and laboratory evaluation revealed elevated liver enzymes (Table I). Prednisolone (1 mg/kg/d) was reinitiated with subsequent normalization of laboratory values (Table I). The prednisolone was tapered after an additional 3 weeks of therapy with no evidence of recurrence. Although the presence of bandemia is frequently seen in systemic infection as a result of bone-marrow activation, it is rarely reported in DHS.1Brown T.S. Appel J.E. Kasteler J.S. Callen J.P. Hypersensitivity reaction in a child due to lamotrigine.Pediatr Dermatol. 1999; 16: 46-49Crossref PubMed Scopus (38) Google Scholar, 2Tichy E. Lam S. Militano U. Bessmertny O. A case of severe thrombocytopenia and antiepileptic hypersensitivity syndrome.J Pediatr Pharmacol Ther. 2003; 8: 29-33PubMed Google Scholar, 3Ben m'rad M. Leclerc-Mercier S. Blanche P. Franck N. Rozenberg F. Fulla Y. et al.Drug-induced hypersensitivity syndrome: clinical and biologic disease patterns in 24 patients.Medicine (Baltimore). 2009; 88: 131-140Crossref PubMed Scopus (143) Google Scholar Our patient's rapid resolution with discontinuation of TMP-SMX and initiation of prednisolone strongly suggests that the bandemia was caused by DHS rather than infection. Various mechanisms causing blood dyscrasias in DHS include cytotoxic antibody-mediated destruction, reversible inhibition of stem cell activity, cessation of myeloid maturation, and induction of cytokine-activated macrophages leading to the development of hemophagocytosis syndrome.3Ben m'rad M. Leclerc-Mercier S. Blanche P. Franck N. Rozenberg F. Fulla Y. et al.Drug-induced hypersensitivity syndrome: clinical and biologic disease patterns in 24 patients.Medicine (Baltimore). 2009; 88: 131-140Crossref PubMed Scopus (143) Google Scholar, 4Lambotte O. Costedoat-Chalumeau N. Amoura Z. Piette J.C. Cacoub P. Drug-induced hemophagocytosis.Am J Med. 2002; 112: 592-593Abstract Full Text Full Text PDF PubMed Scopus (41) Google Scholar The complex inflammatory response and the resultant cytokine storm, notably tumor necrosis factor-alfa among others, can stimulate the bone marrow to release immature neutrophils.5Criado P.R. Criado R.F. Avancini Jde M. Santi C.G. Drug reaction with eosinophilia and systemic symptoms (DRESS)/drug-induced hypersensitivity syndrome (DIHS): a review of current concepts.An Bras Dermatol. 2012; 87: 435-449Crossref PubMed Scopus (123) Google Scholar Recognition of the constellation of clinical findings suggestive of DHS is vital particularly when bandemia is present, as failure to stop the offending medication can lead to exacerbation of the underlying hypersensitivity, with resultant multisystem organ failure. Bands are most commonly associated with infection, but this report confirms that peripheral bands can also be associated with DHS.