1
BRIEF COMMUNICATION
Lymphadenopathy in Patients With Chikungunya Virus Infection Imported From Hispaniola: Case Reports Francesca F. Norman, MBBS, BMedSci,∗ Begoña Monge-Maillo, MD, PhD,∗ Jose-Antonio Perez-Molina, MD, PhD,∗ Fernando de Ory, PhD,† Leticia Franco, PhD,† María-Paz Sánchez-Seco, PhD,† and Rogelio López-Vélez, MD, PhD† ∗ National † Virology
Referral Unit for Tropical Diseases, Infectious Diseases Department, Ramón y Cajal Hospital, IRYCIS, Madrid, Spain; Department, National Microbiology Reference Center, Instituto de Salud Carlos III, Madrid, Spain
DOI: 10.1111/jtm.12204
Chikungunya virus (CHIKV) is currently spreading in the Caribbean and America. Lymphadenopathy, described in infections with other alphaviruses, is not commonly reported in CHIKV infections. Painful lymphadenopathy was found in three of the first six CHIKV infections from the current outbreak diagnosed at a reference center in Madrid, Spain.
C
hikungunya virus (CHIKV) is an RNA alphavirus of the Togaviridae family that produces an acute febrile illness in humans. This emerging virus has caused several large outbreaks in parts of Africa, Asia, and the Indian Ocean Islands and more recently in the Caribbean. More than 850,000 suspected and confirmed cases have been reported during this outbreak in the Caribbean and in South and Central American countries. Imported cases in returning travelers have also been diagnosed in non-endemic countries such as the United States, France, Italy, and Spain.1 More than 75% of human CHIKV infections are symptomatic and the most frequently described features are fever, rash, and joint pains.2 Lymphadenopathy has been described in infections due to other alphaviruses such as O’nyong-nyong virus3 ; yet, it is not a commonly reported feature in CHIKV infections. Case Reports The clinical features for the first six patients diagnosed with CHIKV infections from the current Caribbean outbreak at a Tropical Medicine Reference Center Corresponding Author: Francesca F. Norman, MBBS, BMedSci, National Referral Unit for Tropical Diseases, Infectious Diseases Department, Ramón y Cajal Hospital, Ctra Colmenar Km 9.1, Madrid 28034, Spain. E-mail: [email protected]
in Madrid, Spain, during the month of June 2014 are described. The main, epidemiological, clinical, and laboratory findings for the six patients in the study are summarized in Table 1. All patients (three males, three females, mean age 36.2 years) had recently returned from Hispaniola Island (Dominican Republic or Haiti) and symptoms had started within the 1- to 12-day incubation period for CHIKV. Three patients had traveled to visit friends and relatives (VFRs; patients #1, 2, and 3), one patient was a long-term expatriate who lived in Haiti, and two patients were short-term travelers (38.5∘ C) Rash Odynophagia Joint pains (mainly elbows and ankles) Fever (self-reported) Rash Muscle pain Arthralgia (mainly small joints of hands and feet) Painful inguinal LN (after fever) Fever (self-reported) Rash Conjunctivitis Muscle pain Joint pains (generalized) Painful cervical, axillary, and inguinal LN (after fever)
Fever (>38.5∘ C) Rash Headache Conjunctivitis Muscle pain Dysgeusia Joint pains (elbows, wrists, knees, ankles) Non-tender cervical LN (1 cm) Fever (>38.5∘ C) Joint pains (elbows, wrists, knees, ankles) Back pain Painful cervical, axillary, and inguinal LN (after fever)
Main clinical features
Biochem NSA Transient neutropenia (1,100 cells/μL) and lymphopenia (840 cells/μL)
Transient neutropenia (1,510 cells/μL) and lymphopenia (850 cells/μL) Biochem NSA CRP 18 mg/L Biochem and FBC NSA
Neutropenia (1,300 cells/μL) Biochem NSA CRP 14 mg/L
Transient neutropenia (600 cells/μL) and lymphopenia (190 cells/μL) GPT 63U/L CRP 19 mg/L
Biochem NSA Monocytosis (1,130 cells/μL) CRP46 mg/L
Main laboratory findings
CHIKV PCR neg IgM and IgG pos
CHIKV PCR pos IgM pos IgG neg CHIKV PCR neg IgM and IG pos
CHIKV PCR neg CHIKV IgM and IgG pos
CHIKV PCR pos IgM and IgG neg
CHIKV PCR pos IgM and IgG NA
Diagnosis
DENV PCR neg DENV IgM and IgG neg
DENV PCR NA DENV IgM and IgG neg
DENV PCR neg DENV IgM and IgG neg
DENV PCR neg DENV IgM neg IgG pos HIV neg EBV IgG pos Rubella IgG pos CMV IgG pos DENV PCR neg DENV IgM neg IgG pos HIV neg
DENV PCR neg DENV IgM and IgG NA HIV neg
Other diagnostic tests
M = male; F = female; Biochem = serum biochemistry (including creatinine and liver enzymes); NSA = no significant abnormalities; CHIKV = chikungunya virus; PCR = polymerase chain reaction; neg = negative; pos = positive; NA = not available; DENV = dengue virus; HIV = human immunodeficiency virus; CRP = C-reactive protein; EBV = Epstein-Barr virus; CMV = cytomegalovirus; FBC = full blood count; LN = lymphadenopathy.
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Age (years)
1
Patient number
Table 1 Main, epidemiological, clinical, and laboratory findings for the first six patients diagnosed with CHIKV infections from the current Caribbean outbreak at a Tropical Medicine Reference Center in Madrid, Spain, June 2014
2 Norman et al.
3
Chikungunya Virus and Lymphadenopathy
Three patients (#1, 2, and 4) were diagnosed with acute viremic CHIKV infection (PCR positive) and three (#3, 5, and 6) with recent acute infection (CHIKV IgM positive and CHIKV PCR negative). All patients referred fever and joint pains, and most patients (5/6) presented with a rash. In most cases, joint involvement was symmetrical and involved small joints such as wrists and/or ankles. In four patients (#1, 2, 5, and 6), lymphadenopathy was found. Patient #1 had non-tender bilateral cervical lymphadenopathy (up to 1 cm diameter), whereas patients #2, 5, and 6 had painful lymphadenopathy, which became apparent at the end of/after the febrile period. Other atypical features included conjunctivitis (patients #1 and 6), dysgeusia (patient #1), and odynophagia (patients #3 and 4). For most patients, no significant laboratory abnormalities were found, except for mild (usually transient) neutropenia and/or lymphopenia. Gradual improvement of symptoms with conservative treatment was observed. Discussion CHIKV is currently spreading in the American continent and the surveillance of clinical infections in this new geographical area is essential. Although lymphadenopathy has previously been described in the context of alphavirus infections, this is an uncommonly reported feature in infections caused by CHIKV. Lymphadenopathy, mainly of the cervical area, was reported in nearly half of the patients during an outbreak of O’nyong-nyong fever in south-central Uganda in the late 1990s.3 However, in the case series of CHIKV infection, lymphadenopathy was either not documented, as in the case of the chikungunya outbreak in Northeastern Italy in 2007, or reported infrequently, as in the case of the outbreak in La Réunion in 2006, where lymphadenopathy was found in
BRIEF COMMUNICATION
Lymphadenopathy in Patients With Chikungunya Virus Infection Imported From Hispaniola: Case Reports Francesca F. Norman, MBBS, BMedSci,∗ Begoña Monge-Maillo, MD, PhD,∗ Jose-Antonio Perez-Molina, MD, PhD,∗ Fernando de Ory, PhD,† Leticia Franco, PhD,† María-Paz Sánchez-Seco, PhD,† and Rogelio López-Vélez, MD, PhD† ∗ National † Virology
Referral Unit for Tropical Diseases, Infectious Diseases Department, Ramón y Cajal Hospital, IRYCIS, Madrid, Spain; Department, National Microbiology Reference Center, Instituto de Salud Carlos III, Madrid, Spain
DOI: 10.1111/jtm.12204
Chikungunya virus (CHIKV) is currently spreading in the Caribbean and America. Lymphadenopathy, described in infections with other alphaviruses, is not commonly reported in CHIKV infections. Painful lymphadenopathy was found in three of the first six CHIKV infections from the current outbreak diagnosed at a reference center in Madrid, Spain.
C
hikungunya virus (CHIKV) is an RNA alphavirus of the Togaviridae family that produces an acute febrile illness in humans. This emerging virus has caused several large outbreaks in parts of Africa, Asia, and the Indian Ocean Islands and more recently in the Caribbean. More than 850,000 suspected and confirmed cases have been reported during this outbreak in the Caribbean and in South and Central American countries. Imported cases in returning travelers have also been diagnosed in non-endemic countries such as the United States, France, Italy, and Spain.1 More than 75% of human CHIKV infections are symptomatic and the most frequently described features are fever, rash, and joint pains.2 Lymphadenopathy has been described in infections due to other alphaviruses such as O’nyong-nyong virus3 ; yet, it is not a commonly reported feature in CHIKV infections. Case Reports The clinical features for the first six patients diagnosed with CHIKV infections from the current Caribbean outbreak at a Tropical Medicine Reference Center Corresponding Author: Francesca F. Norman, MBBS, BMedSci, National Referral Unit for Tropical Diseases, Infectious Diseases Department, Ramón y Cajal Hospital, Ctra Colmenar Km 9.1, Madrid 28034, Spain. E-mail: [email protected]
in Madrid, Spain, during the month of June 2014 are described. The main, epidemiological, clinical, and laboratory findings for the six patients in the study are summarized in Table 1. All patients (three males, three females, mean age 36.2 years) had recently returned from Hispaniola Island (Dominican Republic or Haiti) and symptoms had started within the 1- to 12-day incubation period for CHIKV. Three patients had traveled to visit friends and relatives (VFRs; patients #1, 2, and 3), one patient was a long-term expatriate who lived in Haiti, and two patients were short-term travelers (38.5∘ C) Rash Odynophagia Joint pains (mainly elbows and ankles) Fever (self-reported) Rash Muscle pain Arthralgia (mainly small joints of hands and feet) Painful inguinal LN (after fever) Fever (self-reported) Rash Conjunctivitis Muscle pain Joint pains (generalized) Painful cervical, axillary, and inguinal LN (after fever)
Fever (>38.5∘ C) Rash Headache Conjunctivitis Muscle pain Dysgeusia Joint pains (elbows, wrists, knees, ankles) Non-tender cervical LN (1 cm) Fever (>38.5∘ C) Joint pains (elbows, wrists, knees, ankles) Back pain Painful cervical, axillary, and inguinal LN (after fever)
Main clinical features
Biochem NSA Transient neutropenia (1,100 cells/μL) and lymphopenia (840 cells/μL)
Transient neutropenia (1,510 cells/μL) and lymphopenia (850 cells/μL) Biochem NSA CRP 18 mg/L Biochem and FBC NSA
Neutropenia (1,300 cells/μL) Biochem NSA CRP 14 mg/L
Transient neutropenia (600 cells/μL) and lymphopenia (190 cells/μL) GPT 63U/L CRP 19 mg/L
Biochem NSA Monocytosis (1,130 cells/μL) CRP46 mg/L
Main laboratory findings
CHIKV PCR neg IgM and IgG pos
CHIKV PCR pos IgM pos IgG neg CHIKV PCR neg IgM and IG pos
CHIKV PCR neg CHIKV IgM and IgG pos
CHIKV PCR pos IgM and IgG neg
CHIKV PCR pos IgM and IgG NA
Diagnosis
DENV PCR neg DENV IgM and IgG neg
DENV PCR NA DENV IgM and IgG neg
DENV PCR neg DENV IgM and IgG neg
DENV PCR neg DENV IgM neg IgG pos HIV neg EBV IgG pos Rubella IgG pos CMV IgG pos DENV PCR neg DENV IgM neg IgG pos HIV neg
DENV PCR neg DENV IgM and IgG NA HIV neg
Other diagnostic tests
M = male; F = female; Biochem = serum biochemistry (including creatinine and liver enzymes); NSA = no significant abnormalities; CHIKV = chikungunya virus; PCR = polymerase chain reaction; neg = negative; pos = positive; NA = not available; DENV = dengue virus; HIV = human immunodeficiency virus; CRP = C-reactive protein; EBV = Epstein-Barr virus; CMV = cytomegalovirus; FBC = full blood count; LN = lymphadenopathy.
32
Age (years)
1
Patient number
Table 1 Main, epidemiological, clinical, and laboratory findings for the first six patients diagnosed with CHIKV infections from the current Caribbean outbreak at a Tropical Medicine Reference Center in Madrid, Spain, June 2014
2 Norman et al.
3
Chikungunya Virus and Lymphadenopathy
Three patients (#1, 2, and 4) were diagnosed with acute viremic CHIKV infection (PCR positive) and three (#3, 5, and 6) with recent acute infection (CHIKV IgM positive and CHIKV PCR negative). All patients referred fever and joint pains, and most patients (5/6) presented with a rash. In most cases, joint involvement was symmetrical and involved small joints such as wrists and/or ankles. In four patients (#1, 2, 5, and 6), lymphadenopathy was found. Patient #1 had non-tender bilateral cervical lymphadenopathy (up to 1 cm diameter), whereas patients #2, 5, and 6 had painful lymphadenopathy, which became apparent at the end of/after the febrile period. Other atypical features included conjunctivitis (patients #1 and 6), dysgeusia (patient #1), and odynophagia (patients #3 and 4). For most patients, no significant laboratory abnormalities were found, except for mild (usually transient) neutropenia and/or lymphopenia. Gradual improvement of symptoms with conservative treatment was observed. Discussion CHIKV is currently spreading in the American continent and the surveillance of clinical infections in this new geographical area is essential. Although lymphadenopathy has previously been described in the context of alphavirus infections, this is an uncommonly reported feature in infections caused by CHIKV. Lymphadenopathy, mainly of the cervical area, was reported in nearly half of the patients during an outbreak of O’nyong-nyong fever in south-central Uganda in the late 1990s.3 However, in the case series of CHIKV infection, lymphadenopathy was either not documented, as in the case of the chikungunya outbreak in Northeastern Italy in 2007, or reported infrequently, as in the case of the outbreak in La Réunion in 2006, where lymphadenopathy was found in
