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LEPROSY

Leprosy is a chronic infection caused by Mycobacterium leprae, an obligate, intracellular, Gram-


positive, acid-fast microorganism. The disease mainly affects skin, nasal mucosa, and peripheral
nerves.

CliniCal Findings

Leprosy is primarily a disease of developing countries, especially in the tropical areas. India has
two thirds of the global leprosy burden. In the United States, new indigenous cases are reported
mainly in Louisiana and Texas. The prevalence of leprosy has been decreasing in the past
decade because of the effectiveness of multidrug therapy. Mycobacterium leprae is an
intracellular organism most commonly transmitted from human to human. The course and
presentation of an individual infected with M. leprae depends on the host response to the
bacillus. The incubation period of leprosy is variable, on average 5 years. The organism is of low
infectivity and transmission requires prolonged and/or close contact. The portal of entry is
thought to be skin, upper respiratory tract, particularly the nasal mucosa. The spectrum of clinical
presentation and histopathologic findings of leprosy are currently classified according to the
RidleyJopling classification. At one end of the spectrum is tuberculoid leprosy, which is a
paucibacillary form with few lesions. On the other end is lepromatous leprosy, in which there are
numerous lesions with myriad bacilli. In between are the clinical forms classified as borderline-
tuberculoid, borderline, and borderline-lepromatous leprosy. This clinical-histologic
classification has been shown to correlate closely with the level of cell-mediated
immunity to the pathogen. Indeterminate leprosy is a form better recognized in the endemic
regions, seen before the appearance of well-developed lesions of leprosy. It usually manifests as
single or multiple ill-defined hypopigmented or slightly erythematous macules, usually on the
limbs. Slight impairment of sensation may be present. Most indeterminate leprosy lesions heal
spontaneously, but approximately 25% of cases progress. Tuberculoid leprosy is a relatively
stable form seen in patients with strong immunologic host resistance and a markedly positive
lepromin test. Very well demarcated annular patches or plaques with raised erythematous
borders and central clearing are distributed asymmetrically on the trunk or extremities. Sensory
impairment is an essential feature and enlarging regional nerves often lead to palsy. The lesion is
characteristically anesthetic and anhidrotic. Borderline-tuberculoid leprosy is usually associated
with more numerous, smaller lesions than classic tuberculoid leprosy. Hair impairment and
hypoesthesia are more prevalent.

Borderline leprosy represents the middle of the spectrum; but it is unstable, with patients quickly
upgrading or downgrading to a more stable stage. Cutaneous lesions are larger, usually ill-
defined, erythematous or copper-colored, annular patches or plaques (Fig. 3-42). Borderline-
lepromatous leprosy has more numerous and poorly defined lesions than borderline leprosy.
These lesions are shinier and less anesthetic than the tuberculoid type. Nodular lesions may be
present. Lepromatous leprosy occurs in patients with minimal or absent host response (Fig. 3-
43). The cutaneous lesions are usually symmetric, poorly demarcated, erythematous and
hypopigmented macules, patches, and nodules, frequently involving the earlobes and nasal
mucosa. Multiple facial nodules, which spare the eyebrows, give a classical leonine appearance.
When local nerves are involved, lepromatous leprosy causes hypoesthesia of the affected areas.
Multiple autoantibodies are frequently detected in lepromatous leprosy, and there is
an increased incidence of vitiligo.

Histoid leprosya rare, nodular variant of lepromatous leprosyusually develops in


longstanding cases, possibly associated with drug resistance. It is characterized by cutaneous
and/or subcutaneous nodules and plaques. Erythema nodosum leprosum is an immune-complex
mediated reaction associated with multidrug therapy. It occurs in 25% to 70% of lepromatous
leprosy cases, and occasionally in borderline-lepromatous cases during therapy. The clinical
features include widespread eruptions of painful, erythematous, and violaceous nodules,
often involving the extremities, and associated with systemic symptoms. Individual lesions last
for 1 to 3 weeks. Lucios phenomenon, a diffuse non-nodular form of lepromatous leprosy, is
primarily observed in Mexican patients, and associated with irregularly shaped, jagged purpuric
lesions, and hemorrhagic ulcers as a result of the underlying vasculitic changes.
HistologiC Features

Indeterminate leprosy is characterized by a superficial and deep perivascular and periadnexal


lymphohistiocytic infiltrate, which involves less than 5% of the dermis. A mild proliferation of
Schwann cells may be observed, but marked neural thickening is usually absent. Bacilli
are only occasionally seen with Fite stain. Skin biopsies of tuberculoid leprosy resemble those of
cutaneous tuberculosis, especially lupus vulgaris (Fig. 3-44). Well-formed granulomas without
caseation can be seen throughout the dermis without a Grenz zone; they are
composed of epithelioid cells, giant cells, and lymphocytes; they frequently surround
neurovascular bundles, erector pili muscle, and may destroy the eccrine glands. They can erode
the overlying epidermis and/or extend into peripheral nerves or pilar muscles. Acid-fast bacilli
are rarely identified with the Fite stain. In borderline-tuberculoid leprosy, the non-caseating
granulomas are less evident and nerve destruction is less prominent. The lymphocytic mantles
about tubercles may be incomplete or poorly developed. A subepidermal grenz zone may or may
not be present. Acid-fast bacilli are often absent. Borderline leprosy shows collections of
epithelioid histiocytes with no giant cells and very few lymphocytes. Acid-fast bacilli are easy to
find in this condition.

Borderline-lepromatous granulomas consist of aggregates of lymphocytes and macrophages


containing abundant granular to foamy cytoplasm. Numerous acidfast bacilli are seen with Fite
stain. Lymphocytes and histiocytes infiltrate the nerve, producing laminated perineurium. Sheets
of macrophages with a granular to foamy cytoplasm arranged in a perineural, perivascular,
and periappendiceal fashion characterize lepromatous leprosy (Fig. 3-45). The foamy histiocytes
of leprosy resemble those seen in xanthoma; they are called lepra or Virchow cells. Acid-fast
bacilli load the cytoplasm of macrophages, endothelial cells, sweat glands, nerves,
and Schwann cells. Effacement of the epidermal rete ridges with a distinct Grenz zone is often
present, along with scattered lymphocytes and plasma cells. The histology of histoid leprosy
(Fig. 3-46) is characterized by relatively circumscribed nodules that are composed of
predominantly spindle cells intermixed with small collections of foamy macrophages, and
arranged in a storiform pattern. Because the spindle-shaped cells are of dermal dendritic origin
(expressing factor XIIIa), the histologic findings may closely resemble a fibrous
histiocytoma. Both spindle-shaped cells and foamy macrophages are heavily infected with acid-
fast bacilli. At the sites of preexisting lepromatous leprosy, erythema nodosum leprosum shows a
mixed dermal infiltrate of lymphocytes and a variable number of neutrophils. The cytoplasm of
dermal macrophages contains fragmented acid-fast bacilli. Leukocytoclastic vasculitis
and/or panniculitis may also be present. In Lucios phenomenon, necrotizing vasculitis of
the small dermal vessels is found, often associated with epidermal infarction. Less commonly,
vascular occlusion occurs when the superficial vessels thrombose or
endothelial cells swell.
fiGure 3-43 leprosy. Digits with neurosensory loss undergo tissue destruction (lepromatous
leprosy).

figure 3-42 leprosy. Ill-defined erythematous patches and plaques are present in the face
(borderline leprosy).

fiGure 3-44 tuberculoid leprosy. a, A non-necrotizing granulomatous reaction is present. B,


Well-formed epithelioid granulomas are noted with a rim of lymphocytes.

fiGure 3-45 lepromatous leprosy. a, Dense diffuse sheets of histiocytes are present. B, the
infiltrate includes many foamy histiocytes. c, Acid-fast bacilli are numerous.

fiGure 3-46 Histiocytoid leprosy. A dermal fibromalike lesion is identified.

anCillary studies

Fite stain helps to identify microorganisms. Polymerase chain reaction tests are more sensitive.
diFFerential diagnosis

Sarcoidosis may be difficult to differentiate from tuberculoid leprosy if the Fite stain is negative.
Finding the elongate tuberculoid leprosy lesions that follow neurovascular bundles and the
remnants of nerves (via silver stain) within granulomas are helpful clues. Cutaneous
tuberculosis and tuberculoid leprosy are histologically similar. Culture and clinical findings are
important in differentiating these two diseases. Any tendency to involve the nerves points toward
a diagnosis of leprosy. Similar to lepromatous leprosy, sheets of foamy histiocytes occur in
xanthoma. However, Fite stain is negative in the latter. The round intracytoplasmic inclusions
within the histiocytes of rhinoscleroma and histoplasmosis distinguish these from lepromatous
leprosy. Granular cell tumor may mimic lepromatous leprosy because the neoplastic cells have a
perineural distribution and granular cytoplasm. However, a granular cell tumor is usually
overlaid by pseudoepitheliomatous hyperplasia and the cytoplasm appears more eosinophilic
than the macrophages in leprosy.

Prognosis and treatment


Multidrug chemotherapy is directed at the infection itself or at a reactional state. Multiple
different regimens are currently available; the cure rate is over 80%.