1. Leprosy in the USA & Abroad: What the Family Physician Can Do AAFP Global Health Workshop Sept 7, 2012
Ronald Pust MD
Dept of Family & Community Medicine
University of Arizona in Tucson
Arizona Leprosy Clinic
USPHS National Hansen’s Disease Program

2. Leprosy in the USA & Abroad: What the Family Physician Can Do
Learning Objectives
The participants will be able to:
Compare and contrast the pathobiology, epidemiological trends, and relative public health importance of leprosy and tuberculosis in North America and in developing nations
2. Suspect leprosy, examining patients for its skin, EENT and peripheral nerve signs, including the use of slit- skin smears or biopsies and graded monofilaments by primary care clinicians.
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3. Learning Objectives Continued
3. Delineate the implications for diagnosis, treatment and public health of dividing leprosy into WHO/Ridley- Jopling five clinical types: Multibacillary (LL, BL, BB) and Paucibacillary (BT, TT).
4. Contrast the clinical features and “emergency” treatment of immunologic reactions in leprosy: Type I (“up-grading”) in borderline (BT, BB, BL) vs. Type II (ENL) in lepromatous (BL, LL) leprosy.
5. Compare the "unmasking" of underlying paucibacillary leprosy via a Type I “upgrading” reaction due to antiretroviral treatment of AIDS patients to the immune reconstitution inflammatory syndrome [IRIS] in tuberculosis patients who have AIDS.

4. Abstract
Leprosy and its complications can be diagnosed and treated here and abroad by family physicians, who possess the diverse skilled needed to manage its diverse manifestations within a primary care context.
Three simple affinities of Mycobacterium leprae predict and summarize the protean manifestations of clinical leprosy. In this session, participants will become proficient in suspecting, diagnosing and treating leprosy, including its ENT and limb complications. Powerpoint photos from the presenter's current practice will illustrate leprosy's clinical spectrum. Leprosy often first presents as an acute immunologic "reaction," which, if severe, can be an emergency. The presenter will demonstrate physical findings in a volunteer Hansen's patient, if available.
Resources in the USA and abroad that are publically accessible to clinicians and patients will be stressed.

6. Leprosy’s Spectrum: Lepromatous / Borderline / Tuberculoid Recognition, Regimens, Reactions, Rehabilitation and Resources

7. Recognition
LEPROSY IS A CHRONIC, INFECTIOUS HUMAN DISEASE WHICH PRIMARILY INVOLVES:
SKIN
PERIPHERAL NERVES (at
their most superficial points)
EYES (anterior chamber)
NOSE
Why these body areas? What do they have in common?

8. Clinical features follow from 3 unique basic science facts about Mycobacterium leprae
1. COOL : M. leprae grows best at 82 F (28 C)—not 98.6 (37 C).
2. LIKES NERVES, mainly the “cool nerves,” i.e., those closest to the skin surface—whether sensory, motor, or autonomic.
3. SLOW : M. leprae divides every days
(cf hours for many bacteria)

9. SKIN Except where otherwise credited, the patient photos
are from the author’s
National Hansen’s Disease Program clinic in Arizona.

10. PERIPHERAL
NERVES, especially
where superficial
Here: the recurrent
auricular nerve, distal to its emergence from behind and under the
S-C-Mastoid muscle.

11. EYES [anterior chamber]: iritis in LL leprosy “reaction” [here]
or damage to nerves V [sensory] or VII [motor] in BL,BB, or BT
Photo via USPHS National Hansen’s Disease Program, Baton Rouge, Louisiana

12. MUCOUS MEMBRANES: mainly nasal (cooler temperature)
Photo R. Pust, Papua New Guinea,1977

13. DIAGNOSTIC CRITERIA
for Leprosy
ANESTHETIC SKIN LESIONS
“Leprosy until ‘ruled out’,”especially if from endemic nation
ENLARGED PERIPHERAL NERVES
which usually have loss of motor and/or sensory function
ACID FAST BACILLI IN SKIN SMEARS
Mainly in multibacillary [ = LL,BL,BB ]
SKIN BIOPSY: May show granulomas
in paucibacillary leprosy [ = BT, TT)
or AFB in multibacillary [ LL,BL,BB ]

15. Can you get leprosy from an armadillo ?? Consult article in
NEJM, 2011 from
Gulf Coast states and
Nat. Hansen’s Disease
Program [NHDP]
Photo via NHDP archives

16. TRANSMISSION & INCUBATION PERIOD
UNTREATED LEPROMATOUS PATIENTS – RESPIRATORY ROUTE? YES
DIRECT SKIN CONTACT? unlikely
ARMADILLOS? possibly
SOIL OR VEGETATION? unlikely
INCUBATION PERIOD AVERAGE 3 – 5 YEARS, but can be decades
Epidemiology is hampered because no reliable DTH skin test or serologic markers.

17. “Immuno-Clinical” Spectrum of Leprosy [Ridley-Jopling]

18. Classifications within the Immuno-Clinical Spectrum of Leprosy
ffrf
Source: Pust R, Campos-Outcalt D, Postgraduate Med.,1985 [based on several primary sources]

19. Spectrum of Cases from TT to LL
Clinical Photos are from…
Browne S. Early Recognition of Leprosy
[the 3 composite photo/slides introducing tuberculoid, borderline, and lepromatous]
Arizona Hansen’s Disease Clinic at Maricopa County Dept of Public Health in Phoenix, Arizona
[clinical photos / brief patient histories]

20. Early loss of sensation (and perhaps of motor function—especially if
Tuberculoid leprosy:
High CMI, few AFB
Circumscribed
anesthetic macules or
plaques
Early loss of sensation
(and perhaps of motor
function—especially if
Type I “reversal”
immunologic reaction
Four photos via the late
Dr. Stanley Browne
[Uzuakoli Leprosy
Hospital, Nigeria]

21. Tuberculoid:
Filipino boy of 10, from
Yuma, Arizona with
giant hypopigmented,
anesthetic macules;
but no motor loss

22. Tuberculoid leprosy in a 35 yr old Arizona Hispanic cowboy:
Sensory loss, plus R & L ulnar & R median motor nerve loss

23. Tuberculoid: Woman,78, Nogales,AZ: insensitive Charcot foot

24. Radiograph of this 78 yr old woman’s Charcot foot, Nogales, AZ

25. Borderline Leprosy:
Moderate CMI, more
diffuse and disparate
lesions, and a few
AFB in skin smears
Photos: Dr. S. Browne

27. Borderline [BT]: M,32 Burns to insensitive hands; motor intact

28. BT: [same] M,32: Anesthetic macules with central healing

29. Lepromatous Leprosy:
Little CMI,
many AFB infiltrating
lesions--and entire skin;
lesions may have no
definitive borders
Sensation loss later, in
“stocking/glove” pattern,
leading to limb damage
Usually little or no motor
loss
Photos: Dr. S. Browne

30. M, 40s, Arizona
Classic ENT features
of lepromatous [LL]
leprosy
- saddle nose [due to
collapsed nasal septum]
- madarosis [loss of eye-
brows] and eyelashes

31. M,40s [same] Destruction/perforation of nasal septum. Differential?

32. M, 40s, from AZ and CA
[born in Colima, MX]
Severe, classic LL
leprosy facies
[He also had
disseminated
coccidioidomycosis]

33. [same M, 40s]
Classic EENT
features of advanced
lepromatous [LL]
leprosy
[and cervical lymph-
adenitis due to
coccidioidomycosis]

34. 18 F, Sonora and AZ
LL leprosy with…
Madarosis [“corrected”
with make-up] and
septal perforation,
with mild saddle nose

35. M, 50s [Chogoria, Kenya]
Lepromatous [likely BL]
…with late disabilities
over many years
due to secondary
eye and limb damage
from gradual sensation
loss

36. prior osteomyelitis and/or trauma due to lack of sensation
M, 50s [same patient]
Lepromatous leprosy
Hand and foot
damage from repeated
prior osteomyelitis and/or
trauma due to
lack of sensation
3 Kenya photos, Kenya, R Pust, 2003

37. Review of Leprosy Diagnosis
Clinical exam for enlarged/tender nerves
Clinical exam for skin anesthesia, best with graded-diameter filament set, if available
Slit-skin smears, six-site, stained for AFB [also used to monitor treatment every 6-12 months in multi-bacillary leprosy]
Skin punch biopsy, if histopathology is available
No useful blood or skin test [in contrast to TB]
Physical exam more useful than history or lab

38. Population survey for
Leprosy in [then] high-
prevalence population:
Papua New Guinea, 1974
Leprosy is now decreasing
world-wide, possibly
due to case-finding and
improved, multi-drug
treatment—and also due to
BCG vaccine directed at
tuberculosis--which is
increasing due to HIV.

39. Clinical exam protocol
to find enlarged
(and/or tender)
superficial nerves,
during surveys or
in evaluating persons
suspected of having
leprosy.

40. Semmes-Weinstein filaments for quantitative sensory testing
The 10 gram [5.07] S-W filament, now in wide use to detect loss of protective
sensation in diabetics’ feet, came from leprosy research using~20 filament sizes

41. Slit-skin smear technique Pressure = hemostasis and “anesthesia”
With a No. 15 scalpel, make
8 mm long x 4 mm deep
incisions at 6 standard
and knees bilaterally.
Apply the “interstitial fluid”
to glass slide, air dry
AFB stain [as for M. tbc]
Count AFB on log scale,
from 1+ to 6 +
Photo, Arizona Hansen’s Clinic, R. Pust

42. AFB in confluent “globi”—too numerous to count, 6+

43. Slit Skin Smears: Log Scale
0 = NONE FOUND IN 100 OIF
1+ = PER 100 OIF
2+ = PER 10 OIF
3+ = PER OIF
4+ = PER OIF
5+ = PER OIF
6+ = PER OIF
(OIF = OIL IMMERSION FIELD)

44. Punch biopsy [4 mm] may be used to confirm or to classify leprosy where histologist is available, but is not a mandatory test

45. SKIN BIOPSY IN LEPROSY PUNCH BIOPSY: 4 mm diameter
MUST BE DEEP ENOUGH TO INCLUDE SUBCUTANEOUS TISSUE AND FAT
FIX PROMPTLY IN AT LEAST 2 cc OF 10% FORMALIN
MAIL for histopathology [no cost to patient]:
NATIONAL HANSEN’S DISEASE PROGRAM Physicians Park Drive
Baton Rouge, LA 70816
[ Toll-free for all consults]

46. Regimens Regimen and duration is more extensive in multibacillary [LL,
BL and BB] leprosy than in paucibacillary [BT and TT]

47. Regimens WHO LEPROSY REGIMENS PAUCIBACILLARY : 6 Months
Dapsone 100 mg daily
Rifampin 600 mg monthly
MULTIBACILLARY: 12 Months
Clofazimine 300 mg monthly
plus 50 mg daily
USA LEPROSY REGIMENS: All daily
PAUCIBACILLARY: 12 Months (“2 drugs for 1 year”)
Dapsone 100 mg daily
Rifampin 600 mg daily
MULTIBACILLARY: 24 Months (“3 drugs for 2 years”)
Dapsone 100 mg and Rifampin 600 mg daily
Clofazimine 50 mg daily

48. WHO REGIMEN for multibacillary leprosy: Monthly “blister” pack
Dapsone 100 mg daily
Rifampin 600 mg monthly--DOT
Clofazimine 300 mg monthly—DOT
plus 50 mg daily

49. MONITORING RESPONSE TO TREATMENT IN LEPROSY
EXAMINATION OF EYES, HANDS AND FEET for complications [due to insensitivity]
EXAMINATION OF SKIN for lesion regression
EXAMINATION for Type I or Type II “reactions”
REPEAT SKIN SMEARS q months in multibacillary LL, BL, BB] patients
REPEAT BIOPSY in 6-12 months in paucibacillary [BT, TT] patients [rarely needed if patient is adherent to drug regimen]

50. Immunologic reactions in leprosy
Type 1 = “upgrading” reaction [as CMI increases]
Occurs in BT,BB,BL; often during/after Rx
Inflammation, edema of nerves and “old” skin lesions
If severe, can lead over days to permanent loss of motor nerve function. Rx: Prednisone mg
The only true emergency in leprosy
Type 2 = ENL [erythema nodosum leprosum]
Occurs in LL & BL; unpredictable in onset, duration
Large subdermal nodules, often edema, fever, systemic malaise; sometimes iritis or orchitis
Rx: Thalidomide 400mg/day; may start with steroids

51. Type I reaction=“upgrading”
[~ Coombs type 4 =
Delayed-type hypersensitivity]
Occurs as cell-mediated
immunity increases, i.e.,
“upgrades,” shifting toward
tuberculoid end of spectrum
58 year old baker with Borderline [BB] first seen when in reaction.
Many leprosy patients are
first seen in reaction !

52. JB, 19 year old baseball outfielder on Milwaukee Brewers Phoenix farm team,
Recruited from Dominican
Republic, he bats and throws right-handed.
Comes to you after 3 months of management by the Brewers’ hand surgeon…

53. …who has drained serous fluid from a right extensor tendon
…who has drained serous fluid from a right extensor tendon Other than the healed surgical incision, what do you notice?

54. Type II Reaction [Coombs type 3 = immune complex]
Erythema Nodosum Leprosum [ENL]
Pt has fever, malaise and many red nodules elsewhere

55. Classic distribution of ENL: extensor surface of thighs & forearms

56. Case Report to USPHS
NHDP in Baton Rouge
Since this patient
is LL with 6+ skin
AFB smears,
you examine his11
household contacts.

57. Rehabilitation with Ronald Favors, pedorthotist

58. Protective modifications prevent further damage
to hands and feet

59. Resources RELATED WEBSITES and CDs
American Leprosy Missions. URL:
The British Leprosy Relief Association (LEPRA) URL: (includes journal, Leprosy Review)
International Federation of Anti-Leprosy Associations. URL:
USPHS National Hansen’s Disease Program (NHDP) website (Toll free )
NHDP: CD of 5 videos on clinical leprosy (available via R. Pust)
World Health Organization Action Programme for the Elimination of Leprosy. URL:

60. Review—The final “R”

61. One final case:
[from National Hansen’s
Disease Program files]:
What type of leprosy
does this man have?
How would you prove it?

62. Leprosy…and its stigma:
Boot Hill Cemetery,
Tombstone, Arizona
[80 miles SE of Tucson]
“Two Chinese
died of leprosy” c.1882
[recent photograph
by R. Pust, MD]

63. Have you ever
met this man?