Leprosy/Hansen's Disease and Reactional States
Saturday, January 01, 2011
Optimal therapeutic regimens for Hansen's disease (HD) have not
been established by comparative controlled trials. Therapy is
determined primarily by the bacillary load (i.e., multibacillary
vs. paucibacillary). Multibacillary patients include all
lepromatous and almost all borderline patients (except those near
the tuberculoid pole). Paucibacillary patients are those with
indeterminate, pure tuberculoid, and borderline tuberculoid leprosy
(less than 3-5 skin lesions), in which organisms are absent. The
identification of any mycobacteria in the tissue, or the presence
of more than 5 skin lesions classifies the patient as
multibacillary as far as treatment is concerned. Multifocal neural
leprosy should be treated as multibacillary disease. Other factors
important in determining therapy are the availability of
medications, the likelihood of dapsone resistance, and the
compliance of the patient. The World Health Organization (WHO) has
recommended limited or fixed courses of therapy with multiple
agents to enhance compliance, reduce cost, and manage dapsone
resistance. Because of the unique features of this disease and the
lack of experience of most practitioners in the management of HD,
someone with experience in the treatment of Hansen's disease should
evaluate the patient early in the course and guide therapy. The
management of reactional states is discussed at the end of this
- Paucibacillary patients: dapsone 100 mg/day plus rifampin 600
mg once daily, unsupervised; or rifampin 600 mg once monthly,
supervised for 6 months. For a single lesion, rifampin 600 mg,
ofloxacin 400 mg, and minocycline 100 mg all at one time may be
- Multibacillary patients: dapsone 100 mg/day, clofazimine 50
mg/day, plus rifampin 600 mg once daily unsupervised; or rifampin
600 mg once monthly, supervised for 1-3 years.
- Patients should be followed carefully during treatment. At the
end of multidrug therapy, lesions may still be inflamed.
- In patients intolerant of the standard regimens, minocycline
100 mg/day, ofloxacin 400 mg/day, or clarithromycin 500 mg/day may
be substituted for any of the standard antimicrobials for the
duration of treatment as dictated by the disease classification
(multibacillary vs. paucibacillary).
- All patients treated with multidrug therapy who relapse are
treated as multibacillary disease. If the patient failed standard
multidrug therapy, two new agents should be substituted for the
dapsone and clofazimine in the prior treatment regimen.
- Regular follow-up visits following completion of treatment are
recommended for paucibacillary patients for 2 years and for
multibacillary patients for 5 years.
- The initial evaluation by a physician with experience treating
HD should be performed before any effective therapy has been
- A strong psychological support program is required when
initially diagnosing HD. Patients may feel very stigmatized, and
depression to the point of suicide is possible.
- Rifampin may cause hepatotoxicity. If significant abnormalities
of the liver function tests occur (more than doubling of the serum
glutamic oxaloacetic transaminase (SGOT) or serum
glutamic pyruvic transaminase (SGPT), it should be stopped.
Minocycline, ofloxacin, or clarithromycin in doses noted above can
be substituted. Patients taking rifampin will note a reddish-brown
coloration of their urine, sputum, tears, sweat, and feces.
Rifampin also reduces the effectiveness of OCPs.
- Dapsone regularly causes a fall in hematocrit by increasing
erythrocyte hemolysis. An initial glucose-6-phosphate (G6PD) is
required to screen out those especially susceptible to hemolysis.
Monitor the hematocrit initially at biweekly to monthly intervals
until stable. Methemoglobinemia may occur. Dapsone may also cause
an infectious mononucleosis-like hypersensitivity syndrome, with
fever, myalgias, adenopathy, hepatitis, eosinophilia, and
- Clofazimine regularly causes a red to purple-black coloration
of the skin that is accentuated in the lesions. This is the usual
reason for patient noncompliance and if significant is an
indication to change to an alternative agent. Clofazimine also
causes crampy or burning midabdominal pain with or without
diarrhea. This may be severe at high doses (over 100 mg/day) and
may progress to complete bowel obstruction.
Treatment of reactions
Do not reduce or discontinue effective antibacillary therapy
during reactions if at all possible. For mild reactions, aspirin
and symptomatic measures may be adequate. Severe reactions or those
causing neurologic deficit must be aggressively managed as
H3 type I (reversal, lepra) reaction
- Oral corticosteroids (prednisone 60-80 mg/day) are given
initially to control the reaction.
- Higher doses may be required.
H3 type II (erythema nodosum leprosum) reaction
- Thalidomide up to 400 mg daily is the treatment of choice.
- Corticosteroids 60-80 mg/day are effective and are the initial
therapy for women of childbearing potential.
H3 type I (reversal, lepra) reaction
- These reactions may persist for months to years, so the steroid
dosage is tapered and changed to alternate day over months.
- Clofazimine 300 mg/day may be used as a steroid-sparing agent,
but GI side effects may occur at this dosage. Its efficacy is less
predictable than in type II reactions (see below).
H3 type II (erythema nodosum leprosum) reaction (type II
reactions tend to be more short-lived than type I reactions)
- Reaction controlled:
- Taper off thalidomide and/or corticosteroids over 2-3
- If reaction returns reinstitute therapy.
- Reaction uncontrolled: Increase corticosteroids or add
clofazimine 300 mg/day as a steroid-sparing agent.
- Reactional states may cause rapid and permanent neurologic
deficit. Treat them aggressively.
- Thalidomide is a potent teratogen and is contraindicated in
women of childbearing potential. Thalidomide may also cause a
- Do not reduce or decrease antibacillary therapy during the