Musculoskeletal Manifestations Observed in Patients Diagnosed With Chikungunya Virus in 2 Municipalities of the Brazilian Amazon Region

Abstract

Background 

Chikungunya virus fever is an emerging disease that is rapidly spreading and becoming a global public health issue because of its clinical manifestations that cause physical limitations and high rates of chronification. No studies have characterized musculoskeletal manifestations in Brazilian patients with chikungunya.

Objective 

To describe the musculoskeletal manifestations of patients with chikungunya infection in municipalities of the Brazilian Amazon region.

Methods 

This study was an observational, descriptive, and analytical study conducted from March to May 2018. The gender, age, time of infection, clinical manifestations reported during the acute phase, and results of a physical examination of the musculoskeletal system were collected.

Results 

The medical records of 63 patients with a laboratory confirmation of chikungunya virus fever were analyzed. Eighty-three percent of these patients were women, with a mean age of 50.6 ± 14.5 years and 3.3 ± 3.1 months of infection. The main clinical manifestations reported during the acute phase were arthralgia (100%), fever (91%), and exanthema (65%). The physical examination revealed that the main joints affected by arthralgia resulted in a polyarticular (57%, 5–10 joints) and symmetrical pattern (62%) that mainly affected the ankles (53%) and knees (51%). Regarding arthritis, the most frequently affected area was the wrist (42%), with an oligoarticular pattern (42%, 2–4 joints).

Conclusions 

In general, the clinical manifestations described in the Brazilian Amazon population are similar to those reported in publications from other countries; however, the main arthritis pattern identified is oligoarticular, with a predominance of the wrist. Moreover, the chronicity rate is 48%.

Chikungunya virus fever (CKV) is an emerging disease that is rapidly spreading and becoming a global public health issue because a specific treatment or vaccination is unavailable and because it leads to high morbidity rates and physical incapacity.¹

The word “chikungunya” is derived from the African language Makonde and means “the contorted one.” This name is related to the very painful joint pain caused by the arthritis that characterizes the disease. Previous studies characterized the musculoskeletal condition as an arthralgia, which is usually worse in the morning, can be relieved by light exercises, and can be aggravated by dynamic movements. Ankles, wrists, and small hand joints are the mainly affected joints. Larger joints, such as the knees, shoulders, and spine, may also be affected. Migratory polyarthritis effusions were observed in approximately 70% of cases.²

In most patients, the symptoms disappear after 1 to 3 weeks. However, some patients may experience a relapse of musculoskeletal symptoms in the months that follow the acute disease phase, presenting variable degrees of impairment. Some patients report persistent joint pain during the subsequent months, whereas others still experience pain years later.^3,4

The knowledge of the musculoskeletal conditions of the patients infected with the chikungunya virus has become very relevant since its characterization in Brazil, particularly in the Amazon region. Disease transmission was detected only in 2014 in the city of Oiapoque, state of Amapá in the Brazilian Amazon region. Therefore, this study aims to describe the musculoskeletal manifestations of patients with chikungunya infection in municipalities of the Brazilian Amazon region.

METHODS

A descriptive and analytical observational cross-sectional study was conducted with data collected from March to May 2018. The team responsible for this project analyzed the medical records of both the Medical Specialties Center (MSC) of the Capanema municipality and the Tropical Medicine Center of Pará Federal University (TMC-UFPA) in the Belém municipality to conduct this study.

Sixty-three medical records from patients with a confirmed diagnosis of chikungunya fever who received medical care in Capanema MSC or in TMC-UFPA, were at least 18 years old, were of both genders, and presented any phase of the disease were included in this study. All patients received a diagnosis of CKV based on the positivity of serological tests^5,6 and on being classified as a confirmed case based on the diagnostic criteria for CKV.⁷

In October 2016, the Evandro Chagas Institute confirmed some cases of chikungunya fever in Capanema and Belém, both of which are cities in the state of Pará, Brazil. A team of doctors and medical researchers from TMC-UFPA provided local medical care and support upon a request from the city health department and Evandro Chagas Institute. The team of doctors was composed of a rheumatologist, an infectologist, a family doctor, medical residents in the specialties of rheumatology and infectology, and medical students. The information was collected during the medical consultations and recorded in the medical charts for organizational purposes.

The sample was characterized using a database created with Microsoft Office Excel 2010 software (Microsoft Corporation, EUA). To apply the descriptive statistics, the measures of position were calculated, such as arithmetic mean and the SD. Analytical statistics was used to evaluate the results of the categorical variables with the G test and χ² test of adherence for univariate analyses and G test of independence for bivariate analyses. BioEstat 5.0 software (Instituto de Desenvolvimento Sustentável Mamirauá, Brazil) was used to perform descriptive and analytical statistical analyses. For decision-making purposes, the level of significance adopted was 5%.

Ethical Considerations

This study was conducted in accordance with the principles of the Declaration of Helsinki after receiving approval from the Research Ethics Committee of the UFPA Health Sciences Institute under registration number 2.700.639 (CAAE 84229618.5.0000.0018) on June 8, 2018.

RESULTS

Data from 63 patients who were classified as confirmed cases based on the diagnostic criteria for CKV and who received medical care in MSC Capanema (n = 31) and in TMC-UFPA (n = 32) were evaluated in the present study.

Regarding the general characteristics of the analyzed sample, a considerable statistically significant difference (p < 0.0001) in gender was observed: 52 patients (83%) were women, and 11 (17%) were men. The ages of the analyzed patients ranged from 24 to 84 years, with an average age of 50.6 ± 14.5 years (Table 1). All patients lived in the Amazon region, and most resided in Capanema (52%). A statistically significant difference was noticed for the municipalities of Belém (33%) and Ananindeua (7.9%) (Table 1).

TABLE 1 - Distribution of Patients Infected With Chikungunya Virus Who Were Diagnosed in Pará From 2016 to 2018 After Stratification According to the Age Range and Municipalities of Residence

Variable	Frequency (n)	Percentage (%)
Age range,a y
<40	14	22
40 to 49	15	24
50 to 59	17	27
60 to 69	12	19
≥70	5	8
Age, average ± SD	50.6 ± 14.5 y
Municipality
Capanemab	33	52
Belém	21	33
Ananindeua	5	8
Others	4	6

^ap = 0.8263, χ² test for adherence.

^bp < 0.0001, G test for adherence.

The probable time gap from the beginning of the infection until the medical care was provided by the team involved in this study, ranging from 10 days to 14 months. The average time of infection was 3.3 ± 3.1 months (Table 2).

TABLE 2 - Description of the Probable Interval Between the Infection (in Months) and the Time the Patients Diagnosed With Chikungunya Virus Infection in Pará Received Medical Care (From 2016 to 2018)

	Frequency (n)	Percentage (%)
Probable time of infection, mo
<03a	31	49
≥03	29	46
No information	3	5
Average ± SD	3.3 ± 3.1

^ap = 0.8973, χ² test for adherence.

Regarding the clinical manifestations present during the acute phase, a significant number of patients presented with arthralgia (100%), fever (91%), and exanthema (65%). The mean duration of fever in the acute phase was 3.5 days. A substantial number of patients also presented with arthritis (48%), myalgia (29%), headache (18%), pruritus (16%), and conjunctivitis (13%) (Table 3).

TABLE 3 - Distribution of Signs and Symptoms During the Acute Phase in the Patients Diagnosed With a Chikungunya Virus Infection in Pará From 2016 to 2018

Signs and Symptoms	Frequency (n = 63)	Percentage (%)
Arthralgiaa	63	100
Fevera	57	91
Exanthemaa	41	65
Arthritis	30	48
Myalgia	18	29
Cephalea	11	18
Pruritus	10	16
Conjunctivitis	8	13
Dorsalgia	5	8
Shivering	5	8
Nausea	4	6
Asthenia	4	6
Diarrhea	3	5
Vomiting	2	3
Dizziness	1	2
Lacrimation	1	2
Lower limb edema	1	2
Scrotum Edema	1	2

^ap < 0.0001, G test for adherence.

During the medical consultation, 78% of the patients still presented with arthralgia, and 52% presented with arthritis. The joint pattern determined for arthralgia was polyarticular (5 or more affected joints) and symmetric, mainly affecting the knees and ankles. However, it is important to mention that we considered all the affected joints in the hands (distal and proximal interphalangeal and metacarpophalangeal), and 63.8% of joints were affected in the hands.

In the context of the joint pattern determined for arthritis, a predominance of oligoarthritis that mainly affected the wrists was observed. Similar to the clinical features of arthralgia, hand joints were the main affected joints (51.6%); 5 patients (8%) reported morning stiffness, 2 of whom reported a duration of less than 1 hour (Table 4).

TABLE 4 - Pattern of Affected Joints Observed During the Physical Examination of Patients Infected With Chikungunya Virus Who Were Diagnosed in Pará From 2016 to 2018

Rheumatological Investigation	<3 mo	≥3 mo	Total
	n (%)	n (%)	n (%)
Arthralgia (n = 60)
Yes	25 (53)	22 (47)	47 (78)a
No	6 (46)	7 (54)	13 (22)
No. joints (n = 47)
≤1	0 (0)	3 (100)	3 (6)
2–4	8 (62)	5 (38)	13 (28)
5–10	15 (56)	12 (44)	27 (57)a
>10	2 (50)	2 (50)	4 (9)
Symmetry (n = 49)
Yes	17 (59)	12 (41)	29 (62)a
No	8 (44)	10 (56)	18 (38)
Affected joints
Ankles	15 (60)	10 (40)	25 (53)a
Knees	13 (54)	11 (46)	24 (51)a
Shoulder	9 (47)	10 (53)	19 (40)
Metacarpophalangeal joints	8 (50)	8 (50)	16 (34)
Wrist	9 (60)	6 (40)	15 (32)
Tarsometatarsal joints	8 (67)	4 (33)	12 (26)
Proximal interphalangeal joints (hands)	6 (60)	4 (40)	10 (21)
Elbow	3 (38)	5 (63)	8 (17)
Spine	2 (29)	5 (71)	7 (15)
Cervical	3 (60)	2 (40)	5 (11)
Distal interphalangeal joints (hands)	2 (50)	2 (50)	4 (9)
Hips	1 (50)	1 (50)	2 (4)
Metatarsophalangeal	1 (50)	1 (50)	2 (4)
Proximal interphalangeal (feet)	1 (50)	1 (50)	2 (4)
Distal interphalangeal (feet)	1 (100)	0 (0)	1 (2)
Arthritis (n = 60)
Yes	17 (55)	14 (45)	31 (52)b
No	14 (48)	15 (52)	29 (48)
Symmetry (n = 31)
Yes	7 (41)	10 (59)	17 (55)
No	7 (58)	5 (42)	12 (39)
No. joints (n = 31)
≤1	2 (33)	4 (67)	6 (19)
2–4	6 (46)	7 (54)	13 (42)b
5–10	5 (71)	2 (29)	7 (23)
>10	1 (33)	2 (67)	3 (10)
Affected joints
Wrist	9 (69)	4 (31)	13 (42)
Ankle	6 (60)	4 (40)	10 (32)
Metacarpophalangeal joints	4 (44)	5 (56)	9 (29)
Proximal interphalangeal joints (hands)	4 (67)	2 (33)	6 (19)
Knees	2 (29)	5 (71)	7 (23)
Elbow	2 (40)	3 (60)	5 (16)
Shoulders	3 (60)	2 (40)	5 (16)
Metatarsophalangeal joints	0 (0)	3 (100)	3 (10)
Distal interphalangeal joints (hands)	0 (0)	1 (100)	1 (3)
Proximal interphalangeal joints (feet)	1 (100)	0 (0)	1 (3)
Morning stiffness (n = 60)
Yes	2 (40)	3 (60)	5 (8)
No	29 (53)	26 (47)	55 (92)
Duration (n = 04)
<1 h	0 (0)	2 (100)	2 (50)
≥1 h	1 (50)	1 (50)	2 (50)

^ap < 0.0001, χ² test for adherence.

^bp = 0.0080, G test for adherence.

DISCUSSION

This study is the first to evaluate the effects of chikungunya infection on the musculoskeletal system of patients in the Brazilian Amazon region.

Our group identified a female-to-male infection rate ratio of 4.7 women per man and an average age of 50.6 years. In another study with 1192 people in Bavi Village (India), 509 cases of CKV were confirmed, and the infection rate ratio by gender was 0.8 man per woman.⁸ Another study conducted by Rosario et al.⁹ in the Dominican Republic with 514 patients showed a greater incidence of this disease among women (6.7 women per man) and an average age of 53.7 years, similar to our findings.

According to the Preparedness and Response Plan for Chikungunya Introduction in the Americas of the Pan American Health Organization published in 2011, the expected frequency of symptoms in an acute infection would be fever (76%–100%), polyarthralgia (71%–100%), headache (17%–74%), myalgia (46%–72%), back pain (34%–50%), nausea (50%–69%), vomiting (4%–59%), exanthema (28%–77%), polyarthritis (12%–32%), and conjunctivitis (3%–56%).¹⁰ These data are consistent with the results reported by Mejía and López-Vélez¹¹ and Rosario et al.,⁹ who described the following incidence rates: 95% and 100% for fever, 80% and 92% for polyarthralgia, and 64% and 75% for exanthema, respectively. In our current study, a significant percentage of patients experienced arthralgia (100%), fever (91%), and exanthema (65%), showing similarities with recent studies.

Although high incidence rates have been described in epidemiological reports, no studies examining Brazilian populations have reported the clinical manifestations, prevalence, and duration of the symptoms or the effects on the joints. Other published studies involving Brazilian populations are limited to the clinical pattern that has already been defined by scientists in other countries.

According to the Brazilian Guide on the Clinical Management of Chikungunya Fever published by the Brazilian Health Department, the arthralgia pattern is typically polyarticular, symmetric, and additive and mainly affects the most distal joints.¹² The most commonly affected joints on superior members are the wrists, phalanges, shoulders, and elbows, whereas the most commonly affected joints on inferior members are the ankles, knees, feet, and hips. Some areas that are not typically affected are the vertebrae and temporomandibular and sternoclavicular joints. Usually, the articular symptoms may vary in intensity but not in the anatomical location.^11,13,14 The joint pain is generally intense and can be constant or intermittent.¹⁵

In the present study, patients who developed arthralgia showed a polyarticular and symmetric pattern, and 74.4% reported pain in some small joints in the hands and feet, followed by impairments in the ankles (53%) and knees (51%). Atypical joints such as the vertebrae and temporomandibular and sternoclavicular joints were rarely affected.^12,13 In our study, 25.5% of the patients presented with a vertebral impairment, but no reports were available for the other atypical joints.

The majority of the cases of joint edema displayed symmetric distribution predominantly involving the small joints of the finger, wrists, feet, and ankles.¹⁵ A study by Rosario et al.⁹ identified arthritis in 67% of patients, whereas in our study, the incidence was 52%, with a predominant asymmetric and oligoarticular pattern that involved small joints of the hands and feet (64.5%), wrists (42%), and ankles (39%).

The most frequently affected joints were consistent with literature, but the pattern of affected joints was different from the symmetric and polyarticular pattern reported in other studies.^10,14,16 This difference may be justified by other disease phases observed in the patients analyzed in our study, although the majority of the patients were in the chronic phase, when fewer joints are usually affected than in the acute phase.

Joint stiffness mainly in the interphalangeal joints of the hands and feet, ankles, and wrists, particularly in the morning, has been reported in the literature.¹⁷ Our current study also identified morning stiffness, but only in 8% of the studied patients. Fifty percent of these patients reported a joint stiffness duration of less than 1 hour.

Although 50% to 60% of patients with chikungunya completely recover or present light to moderate sequelae, in some patients the disease evolves to a chronic phase 3 months after the beginning of the infection and can last for years.¹⁸ A recent meta-analysis by Rodríguez-Morales et al.¹⁹ evaluated the prevalence of articular disease after an acute chikungunya infection in 18 selected studies and observed prevalence rates ranging from 25.5% to 40.2%.

In the present study, 48% of the patients were in the chronic phase of the disease and presented persistent musculoskeletal manifestations. Most patients sought medical care due to persistent joint pain and edema, whereas some were experiencing limiting pain. The time required to achieve a complete resolution of symptoms is still unknown, but the symptoms persist for years in some patients.²⁰

We concluded that chronicity of CKV in the Brazilian Amazon region is approximately 48% and that joint symptoms are the main manifestations of this disease after 3 months.