You are on page 1of 3

Am. J. Trop. Med. Hyg., 79(3), 2008, pp.

Copyright © 2008 by The American Society of Tropical Medicine and Hygiene

Short Report: Five-year Experience with Type 1 and Type 2 Reactions in Hansen
Disease at a US Travel Clinic
Jesse T. Jacob, Phyllis Kozarsky, Roberta Dismukes, Vicki Bynoe, Lindsay Margoles, Michael Leonard,
Ildefonso Tellez, and Carlos Franco-Paredes*
Division of Infectious Diseases, Emory University, Atlanta, Georgia; Emory TravelWell Clinic, Atlanta, Georgia; Hospital Infantil de
Mexico, Federico Gomez, Mexico

Abstract. Very few data have been reported on the epidemiology and clinical features of leprosy reactions in
non-endemic settings. We performed a retrospective descriptive analysis to define the frequency and features of Type
1 and Type 2 leprosy reactions in a cohort of patients followed at a US travel and tropical medicine clinic in a 5-year
period. We identified that leprosy reactions presented in 10/14 (71.4%) patients with leprosy seen at our clinic. We
identified that leprosy reactions occur frequently among patients living in non-endemic areas and may occur before the
initiation of multi-drug therapy (MDT), during MDT, or even years after completion of therapy and may produce
significant neurologic sequelae. This group of patients needs long-term clinical monitoring even after completion of
MDT because of the need to continue either anti-inflammatory therapy, presence of severe neurologic sequelae after
reactions, or the potential occurrence of late leprosy reactions.
of the 14 patients with HD were referred to our clinic from
other clinical sites; 2 of the 14 patients were self-referred by
word of mouth in the community. All patients referred by
other clinics were already been diagnosed with HD by clinical
findings and biopsy criteria. Seven of these patients were referred to our clinic by dermatologists and two by neurologists
in Georgia; the other three patients were directly referred to
us by the National Hansen Disease Program (NHDP) in the
United States because these three patients lived in Georgia.
In our clinic, we were responsible for confirming a diagnosis
of leprosy in only the two self-referred patients. However, in
our clinic, we were responsible for supervising MDT or managed leprosy reactions in 13 patients in coordination with the
NHDP medical officer (only 1 patient had already completed
a full course of MDT in Brazil).
Among patients with HD see in our clinic, 10/14 (71%)
were men. The median age at presentation to the TravelWell
Clinic was 47.1 years, and median age at diagnosis was 39
years. Diagnosis of HD was established in all patients by
clinical diagnostic criteria using the 1997 case definition and
by the demonstration of acid-fast bacilli in full-thickness skin
punch biopsy (Table 1). Skin biopsies were done on initial
exam and at the end of treatment to document microbiological improvement. By using the Ridley-Jopling classification,
six patients (42.8%) were classified as having lepromatous forms
(LL), two patients presented with borderline lepromatous
(BL) forms (14.3%), one patient (7.1%) presented with the
borderline borderline (BB) form, one (7.1%) with the tuberculoid form (TT), and the remaining presented with borderline tuberculoid (BT) forms (28.6%; Table 1). Bacterial index
was estimated in only six patients at the initial diagnosis and
was categorized as > 2+ in four patients with either borderline
or lepromatous forms and < 2+ in the one patient with TT.
Most patients originated from Brazil (50%), followed by
Mexico (14%), with one patient each from Somalia, Trinidad
and Tobago, India, the United States, and Vietnam (Table 1).
Of the seven patients from Brazil, three came from a single
family consisting of two parents and a son. All patients were
treated with standard MDT options for an average of 2 years
for multibacillary forms (BT, BB, BL, and LL) and 6 months
for the case of TT; second-line therapy was used in three cases
because of drug toxicity or resistance.

Although the worldwide prevalence of Hansen disease
(HD) has decreased in the era of multi-drug therapy (MDT),
the global incidence of leprosy remains the same, while the
number of annual reported cases in the United States increased by 22% in 2005, suggesting that HD will remain a
clinical and public health issue for the foreseeable future.1–4
The World Health Organization guidelines have simplified
the diagnosis and management of uncomplicated HD. However, the recognition and care of complex patients is challenging because the pathogenesis of leprosy is still unclear in
many aspects. Chief among these are leprosy reactions, which
have been reported to occur in 25–50% of HD patients in
regions with a high prevalence of HD. Outside these areas,
the frequency and severity of leprosy reactions, both Type 1
or reversal reaction and Type 2 or erythema nodosum leprosum, have not been well characterized in the MDT era. By
promoting nerve damage, leprosy reactions contribute significantly to the accompanying disability and deformity associated to leprosy. We were interested in evaluating the frequency and outcome of leprosy reactions in HD patients
seeking medical care in a US travel and tropical medicine
We retrospectively examined our experience with HD reactions over a 5-year period (January 2002 to March 2008).
Medical records of patients with HD seen in Emory University’s TravelWell Clinic were systematically reviewed to assess the frequency and outcomes of leprosy reactions. Variables collected included age, sex, ethnicity, country of origin,
age at diagnosis, start and end dates of MDT, dates of reaction, and reaction treatment. Categorical variables were assessed with frequencies, and numeric variables were described using mean, median, and range. The protocol was
approved by the Emory Institutional Review Board.
Of the 563 patients seen in TravelWell for post-travel clinic
visits from January 2002 to 2007, 14 (2.4%) had HD (Table 1).
Historically, our clinic has served as a referral center for tropical infectious diseases and HD patients in Georgia. In fact, 12

* Address correspondence to Carlos Franco-Paredes, Assistant Professor of Medicine, Division of Infectious Diseases, 550 Peachtree
Street, MOT 7th Floor, TravelWell Clinic, Atlanta, GA 30308.


with an average daily prednisone dose of 30 mg. Skin biopsies were done on initial exam and at the end of treatment to document microbiological improvement. and Puerto Rico.4) 4 (28. only four patients.9 years 21.3 The incidence of Type 1 and Type 2 reactions in endemic areas has been well described.5–11 Other possible risk factors for Type 1 reactions .1) 1 (7.1) 5 (50)§ 5 (50)¶ 16. Hawaii. Dominican Republic. and India. followed by patients from Mexico.0 years 21. Both cases were considered as having late Type 1 reactions because of new skin findings.9) 2 (14.2 Of these. particularly in the western Gulf of Mexico.2 months 3. and during follow-up (Table 1).1) 7 (50) 2 (14. In addition. the majority were recorded in individuals born in Mexico.2 months 3 (30%) 5 (50%) 2 (20%) * Diagnosis of HD was established in all patients by clinical diagnostic criteria using the 1997 CDC case definition15 and by the demonstration of acid-fast bacilli in full-thickness skin punch biopsy.2 We identified that in our population by national origin. All patients with Type 1 reactions were treated with prednisone. Reactions occurred before the use of MDT in three patients (30%). Philippines. Type 2 reactions presented in four patients with LL and one patient with BL. One patient developed foot ulcers that required surgical debridement and antibiotic therapy.1) 1 (7. the majority of HD cases presented in individuals from Brazil. Of these. histopathologic changes. The other six patients with reactions were diagnosed in our clinic at the time of the initial evaluation.4 years 6 (42.6) 1 (7.4%) of patients.453 LEPROSY REACTIONS IN THE UNITED STATES TABLE 1 Characteristics of 14 patients with leprosy seen at a US travel clinic (January 2002–March 2008) Characteristic Frequency (%) Sex Male Female Age at presentation Age at diagnosis* Classification of disease† Lepromatous (LL) Borderline lepromatous (BL) Borderline borderline (BB) Borderline tuberculoid (BT) Tuberculoid (TT) Country of birth Brazil Mexico Somalia Trinidad and Tobago Vietnam India United States Reactions Type 1 Type 2 Time from initiation of MDT to onset of reaction Timing of reaction Before MDT During MDT After MDT‡ Median Range 10 (71.1) 4 (28. Most patients with either Type 1 or Type 2 reactions have required long-term medical follow-up to manage complications associated with permanent neurologic sequelae such as foot drop in 2/10 (20%) and significant sensory loss in lower extremity limbs in 6/10 (60%). In these two patients with Type 1 reactions and prior history of treated BT disease.3) 1 (7.1) 1 (7. during MDT in five patients (50%). § Type 1 reactions presented in three patients with BT and in one patient with BL. of which 5 (50%) were Type 1 and five were Type 2 (50%). ‡ One patient presented 5 years after completion of MDT. or after completion of MDT in two patients (20%). Patients with Type 2 reactions were also treated with prednisone. the second one presented 8 years after completion of MDT. The median time from initiation of MDT to onset of reaction was 16.8–64.2–64.1) 1 (7. Two patients presented late type 1 reactions. The diagnosis of reactions was clinical in all patients and confirmed by biopsy in only 6/10 patients: in four patients with Type 2 reaction and in two patients with Type 1 reaction.1 years 39. some autochthonous cases have also been recognized in the United States. Reactions occurred in 10 (71. Of note.9–149. comparisons with previous biopsies were made. Type 1 reactions presented in three patients with BT and one patient with BL. † Ridley-Jopling classification. One patient with Type 1 reaction and one patient with Type 2 reaction who presented with these reactions before initiation of MDT had significant peripheral nerve deficits. Corticosteroid use lasting > 6 months was required in four (40%) patients with reactions. ¶ Type 2 reactions presented in four patients with LL and in the one patient with BL.3) 1 (7. one patient with BL became pregnant during MDT and subsequently developed a Type 2 reaction in the postpartum period that was successfully treated with thalidomide and prednisone. DISCUSSION According to the most recent data from the National Hansen’s Program in the United States. and evidence of neuritis (Table 1). 75% (125 of 166 cases of HD in 2005) were recorded in foreign-born individuals.2 months. but three (60%) patients with Type 2 reactions required both thalidomide and prednisone to control the reaction. Brazil.6) 47. Both Type 1 and Type 2 reactions can occur anytime within the course of leprosy but are often observed after starting treatment and are considered medical emergencies because they can result in irreversible nerve damage. were diagnosed with these reactions before our initial evaluation and were already receiving therapy for these reactions. two with Type 1 reaction and two with Type 2 reactions.

Schwartz MR. Int J Lepr Other Mycobact Dis 72: 125–133. Truman R. Lea JW. Van Brakel WH. mkleona@emory. 13.4 Type 1 reactions are generally heralded by increasing swelling. Vinayakumar S. This may reflect a selection bias in a non-endemic area because sicker patients will seek medical care more frequently. Lockwood DN. results of a fourteen-year experience. or puberty.12 The diagnosis of Type 2 reactions was clinical and most patients required long-term corticosteroid therapy. Fax: 404-686-4508. World Health Organization classification. Muzaffarullah S. Int J Lepr Other Mycobact Dis 65: 37–44. For example. 12. Torres O. Roberta Dismukes. Vicki Bynoe. Phyllis Kozarsky. we found that leprosy reactions occur frequently in our cohort of patients with equal amounts of Type 1 and Type 2 reactions. 5. pregnancy. 22/67 patients developed reversal reactions. REFERENCES 1. 2000. Lucas SB. positive bacillary index. adenopathy. orchitis. Abel L. With increasing global migration. Byass P. 14. Colston MJ. E-mails: frs7@ cdc. Indeed. Buluba Hospital. Vu HT. 2006. Clinical features and outcome of reversal (type 1) reactions in Hyderabad. Stryjewska 1997. 9. often requiring chronic corticosteroid therapy. or other immune system stimulants. Pennec J. 7. Similarly. Int J Lepr Other Mycobact Dis 67: 270–278. Clinical course of erythema nodosum leprosum: an 11-year cohort study in Hyderabad. Kumar B. Atlanta. Arch Pathol Lab Med 131: 982–986. Roche PW. McAdam KP. de Carsalade GY. In this retrospective study. A Summary of Hansen’s Disease in the United States—2005: National Hansen’s Disease Program HHS/HRSA/BPHC. and Carlos Franco-Paredes.emory. Lepr Rev 64: 325–329. Flageul Anderson H. Suneetha S. 1985–89. Ranque B. during MDT. Nguyen VT. 6. Reddy R. Manandhar R. Boyanton BL. Authors’ addresses: Jesse T. Clin Infect Dis 32: 930–937. in a 14-year French study of leprosy treatment. 2007. Hansen disease in the United States in the 21st Century. can also be precipitated by vaccination. Furthermore. HD should be considered an increasingly relevant infectious disease in many areas of the world including the United States. Accepted for publication May 20. 2001.12–14 HD is often complicated by reactions. Age is an important risk factor for onset and sequelae of reversal reactions in Vietnamese patients with leprosy. which occurs in lepromatous leprosy. Epidemiological characteristics of leprosy reactions: 15 years experience from north India. Khawas Nguyen NB. Tel: 404-686-5885. 8. and tenderness in skin lesions accompanied by increased neuritis associated with pain and loss of function. 550 Peachtree Street. phyllis_kozarsky@emoryhealthcare. where flares lasted a mean of 16. Kaur I. Division of Infectious Gebre S. Risk factors for erythema nodosum leprosum. PLoS Medicine 2: We can conclude from our clinical experience at a US travel and tropical medicine clinic that leprosy reactions represent a significant source of morbidity in patients with HD. 1993. Lockwood DNJ. itellez@emory. Financial support: This study was supported by the grant “Global Health without Travel” of the Global Health Institute of Emory University. India. Leprosy: a primer for Canadian physicians. 4. Bwire R. 2004. Int J Lepr Other Mycobact Dis 61: 8–15. ENL reactions in the multibacillary cases of the AMFES cohort in central Ethiopia: incidence and risk factors. Ildefonso Tellez. GA 30308. arthralgias. Update on leprosy in immigrants in the United States: Status in the year 2000. Reactions in leprosy: an epidemiological study of 386 patients in west Nepal. 2006. Kawuma HJ.3 It generally presents with crops of new tender subcutaneous nodules and may be associated with fever. 3. Clin Infect Dis 44: 33– and 18/67 developed Type 2 reaction after an average of 15 months on 1999.454 JACOB AND OTHERS include age at diagnosis of HD.3. tuberculin skin testing. Pocaterra L. Rinaldi A. Moschella SL. Am J Trop Med Hyg 74: 868–879. . Dogra S. 2005. 11. 10. 2004. Michael Leonard. LeMaster JW. Kearney MT. Nguyen TH. Ooi WW. pathogenesis. Cottenot F. lmmargo@ learnlink. Jacob. leprosy reactions may be more common than previously thought among patients living in non-endemic areas and may occur before the initiation of MDT. Daily multidrug therapy for leprosy. TravelWell Clinic. and cfranco@sph. we suggest longterm follow-up of individuals who have successfully completed appropriate MDT regimens for the potential occurrence of late reactions as seen in two of our patients. or even years after completion of therapy. Type 2 reaction. roberta_dismukes@ emoryhealthcare. Keystone JS. MOT 7th Floor. Wallach D. Stanley JN. The global campaign to eliminate leprosy. and occasionally vasculitis. This mirrors the experience from an 11-year study from India. 2007.5. CMAJ Canadian Medical Association Journal 170: 71–78. 2008. Hospital-based epidemiological study of reactions. patients who have suffered a leprosy reaction require longterm medical monitoring and supportive therapy with rehabilitation and physical therapy. India. Jain S. Schurr E. vicki_bynoe@emoryhealthcare. Spindler E. and dactylitis. 1994. Further research into the epidemiology. Received February 19. Boggild AK. Saunderson P. Alcais A.9 months and required an average of 222 mg of prednisone per month among 55/116 patients. Lepr Rev 71: 318–324. 2. Kain KC.emory. Lepr Rev 65: 190–203. Pham XK. Lindsay Margoles. 1993. erythema. and optimal clinical management of reactions is urgently needed.