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 Table of Contents  
LETTER TO THE EDITOR
Year : 2022  |  Volume : 8  |  Issue : 1  |  Page : 52-54

Correlation between percentage of atypical lymphocytes in peripheral smear and disease severity based on internal organ involvement in drug reaction with eosinophilia and systemic symptoms


1 Department of Dermatology & Venereology, Govt Medical College, Kozhikode, Kerala, India
2 Department of Social and Preventive Medicine, Govt Medical College, Kozhikode, Kerala, India
3 Department of Pathology, Govt Medical College, Kozhikode, Kerala, India

Date of Submission04-Apr-2021
Date of Acceptance30-May-2022
Date of Web Publication11-Jun-2022

Correspondence Address:
Sarita Sasidharanpillai
“Rohini,” Girish Nagar, Nallalom PO, Kozhikode 673027, Kerala
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/ijdd.ijdd_12_21

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How to cite this article:
Neerackal RJ, Mohan D, Archana AG, George B, Govindan A, Bindu CS, Sasidharanpillai S. Correlation between percentage of atypical lymphocytes in peripheral smear and disease severity based on internal organ involvement in drug reaction with eosinophilia and systemic symptoms. Indian J Drugs Dermatol 2022;8:52-4

How to cite this URL:
Neerackal RJ, Mohan D, Archana AG, George B, Govindan A, Bindu CS, Sasidharanpillai S. Correlation between percentage of atypical lymphocytes in peripheral smear and disease severity based on internal organ involvement in drug reaction with eosinophilia and systemic symptoms. Indian J Drugs Dermatol [serial online] 2022 [cited 2022 Sep 29];8:52-4. Available from: https://www.ijdd.in/text.asp?2022/8/1/52/347282



Dear Editor,

Clinical manifestations of drug reaction with eosinophilia and systemic symptoms (DRESS) range from mild forms to severe hypersensitivity reactions.[1] In planning an effective therapeutic strategy, information regarding clinical and laboratory markers of internal organ involvement is of great significance. One previous study (from January 2011 to October 2016) by us identified the presence of atypical lymphocytes in peripheral smear as a predictor of severity of DRESS based on internal organ involvement.[2] Here we tried to determine whether a linear correlation existed between the percentage of atypical lymphocytes in the peripheral smear and the disease severity in DRESS.

We received ethical clearance from the institutional ethics committee. We performed a retrospective analysis of the prospectively collected data of patients who required in-patient management in our tertiary care institution with DRESS from 1.9. 2013 to 31.8.2018 (diagnosed as per the RegiSCAR [registry of severe cutaneous adverse reactions] DRESS validation scoring system).[3],[4] The data were collected from the database of the ongoing study on DRESS in our department. Patients with DRESS who were not evaluated in the dermatology department and patients who were not treated as inpatients in our institution were excluded from the study.

Data regarding age, sex, offending drug, and clinical profile of the affected were collected using a preset proforma. Laboratory data on complete hemogram, absolute eosinophil count, liver function (during hospital stay, absolute eosinophil count, and liver function tests were repeated once in 5 days), and renal function tests and peripheral smear were documented.

DRESS severity score was assigned based on the extent of DRESS-induced internal organ involvement [Table 1]. One point each was added for the clinical features identified as evidence of severe DRESS by the French Society of Dermatology. Two points were awarded for features considered as indicators life-threatening DRESS by the French Society of Dermatology.[1] Severe hepatitis was defined as hyperbilirubinemia with elevated liver transaminases.[5]
Table 1: Drug reaction with eosinophilia and systemic symptoms (DRESS) severity score

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The data were entered in Microsoft Excel and analyzed with Statistical Package for the Social Sciences (SPSS) software program, version 18.0. Linear correlation between the disease severity score and the percentage of atypical lymphocytes in the peripheral smear was analyzed using the Pearson correlation coefficient. A value of P < 0.05 was considered statistically significant. To avoid the effects of confounding variables such as age, sex, and diagnostic delay, linear regression analysis was performed. Among the 82 patients studied, 45 (54.9%) were females. The age of the study group ranged from 2 to 78 years (mean age 38.8 years). A mean diagnostic delay of 10.7 days was documented (diagnostic delay varied from 1 day to 58 days). The main culprit drugs were aromatic anticonvulsants (47, 57.3%) [Table 1].

Of 82 patients, 51 (62.2%) had internal organ involvement. Of 51 patients, 50 patients with internal organ involvement had hepatic function derangement (61% of total). One patient (1.2%) manifested nephritis as the lone feature of internal organ involvement. The hepatic function derangement noted was not severe in 19 (38%) of the 50 cases as they manifested elevated liver transaminases which was less than five times the upper limit of the normal and had no evidence of hyperbilirubinemia. All except one (who also manifested nephritis) of these 19 patients were assigned a severity score of zero. Multiorgan involvement was noted in five patients (6.1% of the total) [Table 2].
Table 2: Internal organ involvement in patients with DRESS severity score of one or more

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Forty-nine patients (59.8%) had a severity score of zero. A score of 1 or >1 was noted in 33 patients (40.2%) with a mean of 0.60. Atypical lymphocytes [Figure 1] and [Figure 2] in peripheral smear ranged from 0% to 30% in the study population with a mean value of 3.1 [Table 3]. A statistically significant linear correlation was observed between the disease severity score and the percentage of atypical lymphocytes in the peripheral smear (P = 0.00). This linear correlation was statistically significant (P = 0.00) on linear regression analysis as well, which was carried out to do away with the effects of confounding variables like age, gender, and diagnostic delay.
Figure 1: Arrow denotes atypical lymphocytes and arrow head shows normal lymphocytes in peripheral smear (Leishman x1000)

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Figure 2: Plasmacytoid lymphocyte in peripheral smear (Leishman x1000)

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Table 3: Percentage of atypical lymphocytes in peripheral smear and DRESS severity score

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We retrieved information from patients with DRESS who received treatment from 2013 onwards only for this retrospective analysis, since before that we used to record whether the peripheral smear showed atypical lymphocytes or not and whether the percentage of atypical lymphocytes (when present) was above 5% or not. Later we have started documenting the exact percentage of atypical lymphocytes in the peripheral smear.

Atypical lymphocytosis is a nonspecific response to a probable antigenic stimulus such as viral infections, DRESS, and graft versus host reaction, where rapid production and early release of immature lymphocytes take place, which are subsequently removed from the circulation before mitosis.[6],[7] Hence, a high percentage of atypical lymphocytes could be a reflection of more intense stimulation by antigen.

Previous studies have recorded advanced age, female gender, drugs such as allopurinol, atypical lymphocytes in peripheral smear, and reactivation of human herpesvirus (HHV)-6 and cytomegalovirus as indicators of bad prognosis in DRESS.[2],[5],[8],[9],[10] But we did not come across any studies that have analyzed the correlation between the percentage of atypical lymphocytes in the peripheral smear and the severity of internal organ involvement in DRESS.

One of the limitations of our study was the fact that human herpesvirus reactivation and HLA association, which are known to affect the disease severity of DRESS, were not evaluated. More prospective studies in different population groups are needed to confirm the linear correlation observed between the percentage of atypical lymphocytes in the peripheral smear and the disease severity in DRESS.

Financial support and sponsorship

Not applicable.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
Descamps V, Ben Saïd B, Sassolas B, Truchetet F, Avenel-Audran M, Girardin P, et al; groupe Toxidermies de la Société française de dermatologie. [Management of drug reaction with eosinophilia and systemic symptoms (DRESS)]. Ann Dermatol Venereol 2010;137:703-8.  Back to cited text no. 1
    
2.
Sasidharanpillai S, Chathoth AT, Khader A, Reena Mariyath OK, Riyaz N, Binitha MP, et al. Predictors of disease severity in drug reaction with eosinophilia and systemic symptoms. Indian J Dermatol Venereol Leprol 2019;85:266-75.  Back to cited text no. 2
[PUBMED]  [Full text]  
3.
Chen YC, Chang CY, Cho YT, Chiu HC, Chu CY Reply to: “using a diagnostic score when reporting the long-term sequelae of the drug reaction with eosinophilia and systemic symptoms.” J Am Acad Dermatol 2013;69:1060-2.  Back to cited text no. 3
    
4.
Kardaun SH, Sidoroff A, Valeyrie-Allanore L, Halevy S, Davidovici BB, Mockenhaupt M, et al. Variability in the clinical pattern of cutaneous side-effects of drugs with systemic symptoms: Does a DRESS syndrome really exist? Br J Dermatol 2007;156:609-11.  Back to cited text no. 4
    
5.
Kumari R, Timshina DK, Thappa DM Drug hypersensitivity syndrome. Indian J Dermatol Venereol Leprol 2011;77:7-15.  Back to cited text no. 5
    
6.
Simon MW The atypical lymphocyte. Int Pediatr 2003;18: 20-2.  Back to cited text no. 6
    
7.
Wood TA, Frenkel EP The atypical lymphocyte. Am J Med 1967;42:923-36.  Back to cited text no. 7
    
8.
Eshki M, Allanore L, Musette P, Milpied B, Grange A, Guillaume JC, et al. Twelve-year analysis of severe cases of drug reaction with eosinophilia and systemic symptoms: A cause of unpredictable multiorgan failure. Arch Dermatol 2009;145:67-72.  Back to cited text no. 8
    
9.
Cacoub P, Musette P, Descamps V, Meyer O, Speirs C, Finzi L, et al. The DRESS syndrome: A literature review. Am J Med 2011;124:588-97.  Back to cited text no. 9
    
10.
Chen YC, Cho YT, Chang CY, Chu CU Drug reaction with eosinophilia and systemic symptoms: A drug-induced hypersensitivity syndrome with variable clinical features. J Dermatol Sin 2013; 31:196-204.  Back to cited text no. 10
    


    Figures

  [Figure 1], [Figure 2]
 
 
    Tables

  [Table 1], [Table 2], [Table 3]



 

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