close attention must be given to fluid and renal sta-
tus. Untreated Weils disease has a mortality rate of
5%40%, usually due to renal failure, less often due to
cardiopulmonary failure or pulmonary hemorrhage.
Late sequelae among survivors of untreated illness
include neuropsychiatric diseases.162
PREVENTION
Water sanitation and rodent control measures will
reduce the incidence of leptospirosis in a community.
There is no vaccine against leptospirosis. Individuals
who expect frequent contact with contaminated water
or soils (e.g., military personnel or adventure travelers)
should consider protective clothing and other ways to
limit exposures or they may decrease the risk of dis-
ease by taking prophylactic doxycycline 200 mg, once
weekly during these periods.158,162
Chapter 184 :: Tuberculosis and Infections with
Atypical Mycobacteria
:: Aisha Sethi
Tuberculosis is still an important worldwide disease.
There were an estimated 9.27 million incident cases
globally of TB in 2007.1 This is an increase from 9.24
million cases in 2006, to 8.3 million cases in 2000 and
6.6 million cases in 1990. Most of the estimated number
of cases in 2007 were in Asia (55%) and Africa (31%),
with small proportions in the Eastern Mediterranean
region (6%), the European region (5%) and the Ameri-
cas (3%). The five countries that ranked first to fifth
in terms of total numbers of cases in 2007 were India,
China, Indonesia, Nigeria, and South Africa. Of the
9.27 million incident cases in 2007, an estimated 1.37
million (14%) were HIV positive; 79% of these HIV-
positive cases were in the African region.
In 2008, a total of 12,898 incident tuberculosis (TB)
cases were reported in the United States; the TB rate
declined 3.8% from 2007 to 4.2 cases per 100,000 popu-
lation, the lowest rate recorded since national report-
ing began in 1953. In 2008, the TB rate in foreign-born
persons in the United States was 10 times higher than
in US-born persons. TB rates among Hispanics and
blacks were nearly eight times higher than among
non-Hispanic whites, and rates among Asians were
nearly 23 times higher than among non-Hispanic
whites. To ensure that TB rates decline further in the
United States, especially among foreign-born persons
and minority populations, TB prevention and control
capacity should be increased. Additional capacity
should be used to (1) improve case management and
contact investigations; (2) intensify outreach, testing,
DIPHTHERIA
29
DIPHTHERIA AT A GLANCE
Classic diphtheria produces adherent gray
membranous pharyngeal lesions, which may
cause lethal airway obstruction. Exotoxin
may cause latent peripheral neuritis or lethal
cardiomyopathy.
Cutaneous diphtheria usually affects the
legs and begins as tender pustules that break
down to punched-out ulcers covered by gray
membranes. It is primarily found in the tropics
Chapter 184
or in travelers returning from these areas.
Diphtheria can be prevented with toxoid
immunization. It is treatable with antibiotics
and antitoxin.
::
Tuberculosis and Infections with Atypical Mycobacteria
and treatment of high-risk and hard-to-reach popu-
lations; (3) enhance treatment and diagnostic tools;
(4) increase scientific research to better understand
TB transmission; and (5) continue collaboration with
other nations to reduce TB globally.2
HIV-positive people are about 20 times more likely
than HIV-negative people to develop TB in countries
with a generalized HIV epidemic, and between 26 and
37 times more likely to develop TB in countries where
HIV prevalence is lower.
The so-called atypical Mycobacteria (Mycobacteria
other than Mycobacteria tuberculosis, or MOTT) cause
skin disease more frequently than does M. tuberculosis.
They exist in various reservoirs in the environment.
Among these organisms are obligate and facultative
pathogens as well as nonpathogens. In contrast to the
obligate pathogens, the latter do not cause disease by
person-to-person spread.
MYCOBACTERIA AND THE
ACQUIRED IMMUNODEFICIENCY
SYNDROME PANDEMIC
The pandemic of acquired immunodeficiency syn-
drome (AIDS), with its profound and progressive
suppression of cellular immune functions, has led
to a resurgence of tuberculosis and the appearance 2225
29 or recognition of new mycobacterial pathogens. The
Mycobacterium avium-intracellulare (MAI) complex
is the most common cause of disseminated bacterial
infections in patients with AIDS in the United States,
but is much less frequently so in Europe. In AIDS
patients, Mycobacterium kansasii is more common
than M. tuberculosis. The incidence of tuberculosis in
patients with AIDS is almost 500 times than that in
the general population. Cutaneous disease in AIDS
patients is frequently caused by MOTT.

TUBERCULOSIS OF THE SKIN

TUBERCULOSIS AT A GLANCE
Section 29

Figure 184-1 Scrofuloderma in an Ethiopian patient.

Infection with Mycobacterium tuberculosis or (Used with permission from Dr. Kassahun Bilcha.)
other very closely related strains, as well as
the inflammatory reaction of the host define,
and the AIDS epidemic have led to an increase in all
::

the disease (tuberculosis, or TB).

forms of TB (Table 184-1).
Bacterial Disease

The two most frequent forms of skin tuberculosis are

One-third of the worlds population is
lupus vulgaris (LV) and scrofuloderma (Fig. 184-1). In the
infected with TB.
tropics, LV is rare, whereas scrofuloderma and verrucous
lesions predominate. LV is more than twice as common
TB is the main cause of death of patients
in women than in men, whereas tuberculosis verrucosa
infected with human immunodeficiency
cutis is more often found in men. Generalized miliary
virus.
tuberculosis is seen in infants (and adults with severe
immunosuppression or AIDS), as is primary inoculation
TB usually affects the lung, but virtually all
tuberculosis. Scrofuloderma usually occurs in adolescents
other organ systems may be involved.
and the elderly, whereas LV may affect all age groups.
TB of the skin is a relatively rare
manifestation with a wide spectrum of
THE MYCOBACTERIUM. Mycobacteria multiply
intracellularly, and are initially found in large numbers
clinical findings depending on the source of
in the tissue.
infection and the immune status of the host.
M. tuberculosis, M. bovis, and, under certain condi-
tions, the attenuated BCG organism cause all forms of
Diagnosis is based on clinical manifestations,
skin tuberculosis.
histopathologic analysis, demonstration
In LV, the bacteria often have virulence as low as that
of the relevant Mycobacteria in tissue or in
of the BCG. Large number of bacteria can be found in
culture and host reaction to M. tuberculosis
the lesions of a primary chancre or of acute miliary
antigen.
tuberculosis; in the other forms, their number in the
lesions is so small that it may be difficult to find them.
Treatment is with standard multidrug
M. tuberculosis may become dormant in the host tissue.
regimens; cases of multidrug-resistant
New diagnostic tools are emerging,4,5 as described
(MDR) TB or extensively multidrug-resistant
below.
(XDR) TB require special attention.

Course and prognosis depend on the

immune status of the host. Treatment is
curative except for patients with a severely
compromised immune system.
EPIDEMIOLOGY
Tuberculosis of the skin has a worldwide distribution.
Once more prevalent in regions with a cold and humid
climate, it now occurs mostly in the tropics. Cutane-
ous TB incidence parallels that of pulmonary TB and
developing countries still account for the majority of
2226 cases in the world. The emergence of resistant strains
THE HOST. The human species is quite susceptible to
infection by M. tuberculosis, with big differences among
populations and individuals. Populations that have been
in long-standing contact with tuberculosis are, in general,
less susceptible than those who have come into contact
with Mycobacteria more recently, presumably reflecting
widespread immunity from subclinical infection. Age,
state of health, environmental factors, and particularly the
immune system are of importance. In Africans, tuberculo-
sis frequently takes an unfavorable course, and tuberculin
sensitivity may be more pronounced than in whites.
TUBERCULIN REACTION (KOCH PHENOM-
ENON). An extract of M. tuberculosis (tuberculin) was
shown to produce a different skin reaction in sensi-
tized individuals than in naive individuals, and this
 TABLE 184-1
29
Classification of Cutaneous Tuberculosis

Host Immune Status Clinical Disease

Exogenous infection Naive
Immune Primary inoculation tuberculosis
Tuberculosis verrucosa cutis
Endogenous spread High Lupus vulgaris
Scrofuloderma
Low Acute miliary tuberculosis
Orificial tuberculosis
Metastatic tuberculous abscess
(tuberculous gumma)

Chapter 184
Tuberculosis due to Bacille Calmette- Naive Normal primary complex-like reaction
Gurin Perforating regional adenitis
Postvaccination lupus vulgaris
Tuberculids Not clear Tuberculids:
Lichen scrofulosorum
Papulonecrotic tuberculid

::
Facultative tuberculids:

Tuberculosis and Infections with Atypical Mycobacteria

Nodular vasculitis
Erythema nodosum

difference became the basis of a widely used diagnostic togenous dissemination (acute miliary tuberculosis of
test. This reaction is a delayed-type hypersensitivity the skin or LV).
reaction, induced by Mycobacteria during primary infec-
tion. This old tuberculin has now been replaced by
purified protein derivative (PPD). More recently, puri- HISTOPATHOLOGY
fied species-specific antigens have been developed.6
Local intradermal injection (the method most widely The hallmark of tuberculosis and infections with some of
used) leads to the local tuberculin reaction, which usu- the slow-growing atypical Mycobacteria is the tubercle: an
ally reaches its maximum intensity after 48 hours. It accumulation of epithelioid histocytes with Langhans-
consists of a sharply circumscribed area of erythema type giant cells among them and a varying amount of
and induration, and in highly hypersensitive recipients caseation necrosis in the center, surrounded by a rim of
or after large doses, a pallid central necrosis may appear. lymphocytes and monocytes. Although this tuberculoid
In an attempt to quantify the tuberculin reaction, granuloma is highly characteristic of several forms of
an assay known as the QuantiFERON-TB Gold test tuberculosis, it may be mimicked by deep fungal infec-
was developed to measure specific antigen-driven tions, syphilis, and leprosy, as well as other diseases. As
interferon- synthesis by whole blood cells and was in leprosy, the histopathologic features of skin tuberculo-
approved by the FDA in 2005. sis may be reflective of the hosts immune status.
Tuberculin sensitivity usually develops 210 weeks
after infection and persists throughout life. The state of
sensitivity of an individual infected with M. tuberculo-
sis is of considerable significance in the pathogenesis of
tuberculosis skin lesions.
In patients with clinical tuberculosis, an increase in
skin sensitivity usually indicates a favorable prognosis,
and in tuberculous skin disease accompanied by high
levels of skin sensitivity, the number of bacteria within
the lesions is small. Tuberculin sensitivity (skin reactiv-
ity) is not necessary for immunity, however, and sensi-
tivity and immunity do not always parallel each other.

ROUTE OF INFECTION. Cutaneous inoculation

leads to a tuberculous chancre or to tuberculosis verru-
cosa cutis (Fig. 184-2), depending on the immunologic
state of the host.
Spread of Mycobacteria may occur by continuous Figure 184-2 Tuberculosis Verrucosa cutis on the foot of
extension of a tuberculous process in the skin (scrofu- an Ethiopian patient. (Used with permission from Dr. Kas-
loderma) by way of the lymphatics (LV), or by hema- sahun Bilcha.) 2227
29 POLYMERASE CHAIN REACTION
PROCEDURE
The polymerase chain reaction (PCR) procedure has
been used increasingly to ascertain the presence of
mycobacterial DNA in skin specimens.7 Although the
detection of specific DNA in tissues has yielded valu-
able information and will conceivably gain importance
in the future, interpretation of the results of these
tests in individual patients is still problematic.8 In one
study, samples from 16 of 20 patients with sarcoidosis
contained mycobacterial DNA, both tuberculous and
nontuberculous.9 In another study of patients with con-
firmed or highly probable cutaneous tuberculosis or
Section 29
PRIMARY INOCULATION
TUBERCULOSIS (TUBERCULOUS
CHANCRE, TUBERCULOUS PRIMARY
COMPLEX)
EPIDEMIOLOGY. Tuberculous chancre and affected
regional lymph nodes constitute the tuberculous pri-
mary complex in the skin. The condition is believed
rare, but its incidence may be underestimated. In some
regions with a high prevalence of tuberculosis and
poor living conditions, primary inoculation tuberculo-
sis of the skin is not unusual. Children are most often
affected.

with erythema induratum, believed to indicate a host

response to the infection, PCR testing showed 100%
sensitivity and specificity in multibacillary disease. In
paucibacillary disease, PCR testing showed 55% sen-
sitivity and specificity, and only 80% of PCR-positive
::
ETIOLOGY AND PATHOGENESIS. Tubercle
bacilli are introduced into the tissue at the site of
minor wounds. Oral lesions may be caused by bovine
bacilli in nonpasteurized milk and occur after mucosal

patients responded to antituberculosis therapy.7 trauma or tooth extraction. Primary inoculation tuber-
culosis is initially multibacillary, but becomes pauci-
Bacterial Disease

bacillary as immunity develops.

QUANTIFERON-TB GOLD (QFT-G)
TEST CLINICAL FINDINGS. The chancre initially
appears 24 weeks after inoculation and presents as
In 2005, the FDA approved QFT-G as an in vitro diag- a small papule, crust, or erosion with little tendency
nostic aid. In this test, blood samples are mixed with to heal. Sites of predilection are the face, including the
antigens and controls. For QFT-G, the antigens include conjunctivae and oral cavity, as well as the hands and
mixtures of synthetic peptides representing two M. lower extremities. A painless ulcer develops, which
tuberculosis proteins: (1) ESAT-6 and (2) CFP-10. After may be quite insignificant or may enlarge to a diam-
incubation of the blood with antigens for 1624 hours, eter of more than 5 cm (Fig. 184-3). It is shallow with
the amount of interferon- (IFN-) is measured. a granular or hemorrhagic base studded with miliary
If the patient is infected with M. tuberculosis, their abscesses or covered by necrotic tissue. The ragged
white blood cells will release IFN- in response to con- edges are undermined and of a reddish-blue hue. As
tact with the TB antigens. The QFT-G results are based the lesions grow older, they become more indurated,
on the amount of IFN- that is released in response to with thick adherent crusts.
the antigens.
Although more sensitive than the tuberculin skin
test, the QFT-G may be negative in patients with early
active tuberculosis and indeterminate results are more
common in immunocompromised individuals and
young children. Another similar assay, the T-SPOT.TB
test, measures the number of IFN--producing T cells
and is currently available in Europe. QFT-G testing
is indicated for diagnosing infection with M. tubercu-
losis, including both TB disease and latent TB infec-
tion. Whenever M. tuberculosis infection or disease is
being diagnosed by any method, the optimal approach
includes coordination with the local or regional public
health TB control programs.

SKIN DISEASES CAUSED

BY MYCOBACTERIUM
TUBERCULOSIS/BOVIS INFECTION
Infection with M. tuberculosis used to be thought to
result in characteristic clinical features.10 However,
with increasing number of cases in immunocompro- Figure 184-3 Primary inoculation tuberculosis. Note tu-
mised individuals and improved diagnostic tools, many berculous chancre on the thigh and regional lymphade-
2228 uncharacteristic manifestations have been discovered. nopathy. A positive tuberculin reaction is noted on the arm.
 Wounds inoculated with tubercle bacilli may heal
temporarily but break down later, giving rise to gran-
ulating ulcers. Mucosal infections result in painless
ulcers or fungating granulomas. Inoculation tuber-
culosis of the finger may present as a painless paro-
nychia. Inoculation of puncture wounds may result in
subcutaneous abscesses.
Slowly progressive, regional lymphadenopathy
develops 38 weeks after the infection (Fig. 184-3) and
may rarely be the only clinical finding. After weeks
or months, cold abscesses may develop that perfo-
rate to the surface of the skin and form sinuses. The
lymph nodes draining the primary glands may also be
involved. Body temperature may be slightly elevated.
The disease may take a more acute course, and in half
of the patients, fever, pain, and swelling simulate a
pyogenic infection. Early, there is an acute nonspecific
inflammatory reaction in both skin and lymph nodes,
and Mycobacteria are easily detected by Fite stain. After
36 weeks, the infiltrate and the regional lymph nodes
acquire a tuberculoid appearance and caseation may
occur.
DIAGNOSIS. Any ulcer with little or no tendency
to heal and unilateral regional lymphadenopathy in a
child should arouse suspicion. Acid-fast organisms are
found in the primary ulcer and draining nodes in the
initial stages of the disease. The diagnosis is confirmed
by bacterial culture. The PPD reaction is negative ini-
tially and later converts to positive (Fig. 184-3).
DIFFERENTIAL DIAGNOSIS. The differential
diagnosis encompasses all disease with a primary
complex (Box 184-1).
COURSE. If untreated, the condition may last up to
12 months. Rarely, LV develops at the site of a healed
tuberculous chancre. The regional lymph nodes usu-
ally calcify.
The primary tuberculous complex usually produces
immunity, but reactivation of the disease may occur.
Hematogenous spread may give rise to tuberculosis
of other organs, particularly of the bones and joints.
It may also lead to acute miliary disease with a fatal
outcome. Erythema nodosum occurs in approximately
10% of cases.
BOX 184-1 DIFFERENTIAL DIAGNOSIS OF
PRIMARY INOCULATION TUBERCULOSIS
Most Likely
Syphilis
Sporotrichosis
Consider
Tularemia
Bartonellosis
Always Rule Out
Other mycobacterioses
TUBERCULOSIS VERRUCOSA CUTIS
29
(WARTY TUBERCULOSIS, PROSECTORS
WART, LUPUS VERRUCOSUS)
ETIOLOGY AND PATHOGENESIS. Tuberculosis
verrucosa cutis is a paucibacillary disorder caused by
exogenous reinfection (inoculation) in previously sen-
sitized individuals with high immunity.
Inoculation occurs at sites of minor wounds or,
rarely, from the patients own sputum. Members of
professional groups handling infectious material are
at risk. Children may become infected playing on con-
taminated ground.
Chapter 184
CLINICAL FINDINGS. Lesions usually occur on the
hands or, in children, on the lower extremities as a small
asymptomatic papule or papulopustule with a purple
inflammatory halo. They become hyperkeratotic and
are often mistaken for a common wart. Slow growth
::
and peripheral expansion lead to the development of a
verrucous plaque with an irregular border (Fig. 184-4).
Tuberculosis and Infections with Atypical Mycobacteria
Fissures discharging pus extend into the underlying
brownish-red to purplish infiltrated base. The lesion usu-
ally is solitary, but multiple lesions may occur. Regional
lymph nodes are rarely affected.
Lesions progress slowly and, if untreated, persist
for many years. Spontaneous involution eventually
occurs, leaving an atrophic scar.
HISTOPATHOLOGY. The most prominent histopatho-
logic features are pseudoepitheliomatous hyperplasia
with marked hyperkeratosis, a dense inflammatory infil-
trate, and abscesses in the superficial dermis or within
the pseudoepitheliomatous rete pegs. Epithelioid cells
and giant cells are found in the upper and middle der-
mis. Typical tubercles are uncommon, and the infiltrate
may be nonspecific.
Figure 184-4 Tuberculosis verrucosa cutis on the back of
the hand. 2229
29 from elsewhere in the body. Spontaneous involution
may occur, and new lesions may arise within old scars.
BOX 184-2 DIFFERENTIAL DIAGNOSIS
Complete healing rarely occurs without therapy.
OF TUBERCULOSIS VERRUCOSA CUTIS
Most Likely CLINICAL FINDINGS. Lesions are usually solitary,
Warts or keratoses but two or more sites may be involved simultane-
ously. In patients with active pulmonary tuberculosis,
Hyperkeratotic lupus vulgaris
multiple foci may develop. In approximately 90% of
Blastomycosis patients, the head and neck are involved. LV usually
Hypertrophic lichen planus starts on the nose, cheek, earlobe, or scalp and slowly
Consider extends onto adjacent regions. Other areas are rarely
Chromomycosis involved.
The initial lesion is a brownish-red, soft or friable
Bromoderma
macule or papule with a smooth or hyperkeratotic sur-
Tertiary syphilis
face. On diascopy, the infiltrate exhibits a typical apple
Section 29

Always Rule Out jelly color. Progression is characterized by elevation, a

Lesions due to other Mycobacteria deeper brownish color (Fig. 184-5), and formation of
a plaque (see Fig. 184-5). Involution in one area with
expansion in another often results in a gyrate outline
border. Ulceration may occur. Hypertrophic forms
::

appear as a soft nodule (see eFig. 184-3.1 in online edi-

Bacterial Disease

DIFFERENTIAL DIAGNOSIS. (Box 184-2)
LUPUS VULGARIS (TUBERCULOSIS
LUPOSA)
EPIDEMIOLOGY. LV is an extremely chronic, pro-
gressive form of cutaneous tuberculosis occurring in
individuals with moderate immunity and a high degree
of tuberculin sensitivity. Once common, LV has declined
steadily in incidence. It has always been less common
in the United States than in Europe. Females appear to
be affected two to three times as often as males; all age
groups are affected equally.
tion) or plaque with a hyperkeratotic surface (eFig.
184-3.2 in online edition). The mucosae may be pri-
marily involved or become affected by the extension
of skin lesions. Infection is manifest as small, soft, gray
or pink papules, ulcers, or friable granulating masses.
After a transient impairment of immunity, particu-
larly after measles (thus the term lupus postexanthe-
maticus), multiple disseminated lesions may arise
simultaneously in different regions of the body as a
consequence of hematogenous spread from a latent
tuberculous focus. During and after the eruption, a
previously positive tuberculin reaction may become
negative but will usually revert to positive as the gen-
eral condition of the patient improves.

ETIOLOGY AND PATHOGENESIS. LV is a post- HISTOPATHOLOGY. The most prominent histo-

primary, paucibacillary form of tuberculosis caused pathologic feature is the formation of typical tubercles.
by hematogenous, lymphatic, or contiguous spread Secondary changes may be superimposed: epidermal

A B

Figure 184-5 A. Slightly raised, brownish plaque of lupus vulgaris. B. Large plaque of lupus vulgaris of 10 years duration
2230 involving the cheek, jaw, and ear.
thinning and atrophy or acanthosis with excessive
hyperkeratosis or pseudoepitheliomatous hyperpla-
29
sia. Acid-fast bacilli are usually not found. Nonspe-
cific inflammatory reactions may partially conceal
the tuberculous structures. Old lesions are composed
chiefly of epithelioid cells and may be impossible to
distinguish from sarcoidal infiltrates (see eFig. 184-4.1
in online edition).

DIAGNOSIS. Typical LV plaques may be recognized

by the softness of the lesions, brownish-red color, and
slow evolution. The apple jelly nodules revealed by
diascopy are highly characteristic; finding them may
be decisive, especially in ulcerated, crusted, or hyper-
keratotic lesions. The result of the tuberculin test is

Chapter 184
strongly positive except during the early phases of
postexanthematic lupus. Bacterial culture results may
be negative, in which case the clinical diagnosis can
usually be supported by positive PCR results for M.
tuberculosis.

::
DIFFERENTIAL DIAGNOSIS. (Box 184-3) Figure 184-6 Lupus vulgaris of long duration that has led

Tuberculosis and Infections with Atypical Mycobacteria

COMPLICATIONS. Involvement of the nasal or
auricular cartilage may result in extensive destruc-
tion and disfigurement (Fig. 184-6). Atrophic scarring,
with or without prior ulceration, is characteristic, as is
recurrence within a scar. Fibrosis may be pronounced
and mutilating.
Dry rhinitis is often the only symptom of early nasal
LV, but lesions may also destroy the cartilage of the
nasal septum. Scarring of the soft palate and laryngeal
stenosis also occur.
COURSE. LV is a very long-term disorder and with-
out therapy progresses over many years to func-
tional impairment and disfiguration (see Fig. 184-6).
Long-standing LV may lead to the development of
carcinoma (see Fig. 184-6). Squamous cell carcino-
mas outnumber basal cell carcinomas by far, and the
risk of metastases is high. In 40% of patients, there is
associated tuberculous lymphadenitis, and 10%20%
have active pulmonary tuberculosis or tuberculosis of
to the destruction of the nose. Ulcerating squamous cell
carcinoma has developed on the upper lip.
the bones and joints.11 Pulmonary tuberculosis is 410
times more frequent in patients with LV than in the
general population.
SCROFULODERMA (TUBERCULOSIS
COLLIQUATIVA CUTIS)
EPIDEMIOLOGY. Prevalence is higher among chil-
dren, adolescents, and the aged.
ETIOLOGY AND PATHOGENESIS. Scrofulo-
derma is subcutaneous tuberculosis leading to cold
abscess formation and a secondary breakdown of the
overlying skin. It may be either multibacillary or pauc-
ibacillary.
Scrofuloderma represents contiguous involvement
of the skin overlying another site of infection (e.g.,
tuberculous lymphadenitis, tuberculosis of bones and
joints, or tuberculous epididymitis).

CLINICAL FINDINGS. Scrofuloderma most often

BOX 184-3 DIFFERENTIAL DIAGNOSIS occurs in the parotidal, submandibular, and supra-
OF LUPUS VULGARIS clavicular regions and may be bilateral. It first pres-
ents as a firm, subcutaneous nodule, usually well
Most Likely defined, freely movable, and asymptomatic. As the
Sarcoidosis lesion enlarges, it softens. After months, liquefaction
Discoid lupus erythematosus with perforation occurs, causing ulcers and sinuses
(Fig. 184-7). The ulcers are linear or serpiginous
Consider
with undermined, inverted, bluish edges and soft,
Lymphocytoma granulating floors. Sinusoidal tracts undermine the
Tertiary syphilis skin. Clefts alternate with soft nodules. Scar tracts
Leprosy develop and bridge ulcerative areas or even stretches
Lupoid leishmaniasis of normal skin. Tuberculin sensitivity is usually
pronounced.
Always Rule Out
Blastomycosis or other deep mycotic infections
HISTOPATHOLOGY. Massive necrosis and abscess
formation in the center of the lesion are nonspecific. 2231
29
Section 29
::
Bacterial Disease
Figure 184-7 Scrofuloderma in the clavicular region.
Note abscess formation, ulceration, and extrusion of puru-
lent and caseous material.
However, the periphery of the abscesses or the mar-
gins of the sinuses contain tuberculoid granulomas.
DIAGNOSIS. If there is an underlying tuberculous
lymphadenitis or bone and joint disease, the diagnosis
usually presents no difficulty. Positive results on cul-
ture confirm the diagnosis.
DIFFERENTIAL DIAGNOSIS. (Box 184-4)
COURSE. Spontaneous healing does occur, but the
course is very protracted, and it may be years before
lesions have been completely replaced by scar tis-
sue. Presence of the typical cribriform scars permits a
correct diagnosis, even after the process has become
quiescent. LV may develop at or near the site of scrofu-
loderma.
BOX 184-4 DIFFERENTIAL DIAGNOSIS
OF SCROFULODERMA
Most Likely
Sporotrichosis
Hidradenitis suppurativa
Consider
Mycobacterium scrofulaceum infection
Syphilitic gummas
Actinomycosis
Severe forms of acne conglobata
Always Rule Out
Mycobacterium avium-intracellulare lymphadenitis
2232
ORIFICIAL TUBERCULOSIS
(TUBERCULOSIS ULCEROSA CUTIS
ET MUCOSAE, ACUTE TUBERCULOUS
ULCER)
ETIOLOGY AND PATHOGENESIS. Orificial
tuberculosis is a rare form of tuberculosis of the mucous
membranes and orifices that is caused by autoinocula-
tion of Mycobacteria from progressive tuberculosis of
internal organs.
The underlying disease is far advanced pulmonary,
intestinal, or, rarely, genitourinary tuberculosis. Myco-
bacteria shed from these foci in large numbers are inoc-
ulated into the mucous membranes.
CLINICAL FINDINGS. A small yellowish or red-
dish nodule appears on the mucosa and breaks down
to form a soft ulcer with a typical punched-out appear-
ance, undermined edges, and circular or irregular bor-
der (Fig. 184-8). The ulcer floor often exhibits multiple
yellowish tubercles and bleeds easily. The surrounding
mucosa is edematous and inflamed. Lesions may be
single or multiple and are extremely painful, resulting
in dysphagia.
The tongue is most frequently affected, particularly
the tip and the lateral margins, but the soft and hard pal-
ates are also common sites. In advanced cases, the lips
are involved, and the oral condition often represents an
extension of ulcerative tuberculosis of the pharynx and
larynx. In patients with intestinal tuberculosis, lesions
develop around the anus, and in females with active
genitourinary disease, the vulva is involved.
HISTOPATHOLOGY. There is a massive nonspe-
cific inflammatory infiltrate and necrosis, but tubercles
with caseation may be found deep in the dermis. Myco-
bacteria are easily demonstrated.
Figure 184-8 Orificial tuberculosis in advanced cavitary
pulmonary tuberculosis.
 BOX 184-5 DIFFERENTIAL DIAGNOSIS
OF ORIFICIAL TUBERCULOSIS
Most Likely
Aphthous ulcers
Consider
Syphilitic lesions (not painful)
Always Rule Out
Squamous cell carcinoma
DIFFERENTIAL DIAGNOSIS. (Box 184-5)
COURSE. Orificial tuberculosis is a symptom of
advanced internal disease and usually portends a fatal
outcome.
SEQUELAE OF BACILLE CALMETTE
GURIN INOCULATION
Vaccination with attenuated bovine BCG appears to pro-
tect infants and young children from the more serious
forms of tuberculosis, but its ability to prevent disease in
adults remains uncertain. In the United States, guidelines
for BCG immunization have been developed.12,13
In the normal course of BCG vaccination, an infiltrated
papule develops after approximately 2 weeks, attains a
size of approximately 10 mm after 612 weeks, ulcerates,
and then slowly heals, leaving a scar. Vaccination may
provoke an accelerated reaction in a previously infected
person. The regional lymph nodes may enlarge, but usu-
ally heal without breaking down. Tuberculin sensitivity
appears 56 weeks after vaccination.
The true incidence of complications caused by
the BCG organism is difficult to ascertain, but it is
extremely low in comparison to the great number
of vaccinations performed in Europe in the past 50
years.14 Problems include the following:
LV at or near the vaccination site (latency of months
to years)
Koch phenomenon in individuals sensitive to
tuberculin [see Section Tuberculin Reaction (Koch
Phenomenon)]
Regional adenitis, sometimes severe and with sys-
temic symptoms, more often in children
After deep injection, local abscesses, excessive ulcer-
ation
Scrofuloderma with suppuration for 612 months
Generalized tuberculid-like reactions (rare)
Generalized adenitis, osteitis, organ tuberculosis
(e.g., in the joints) occasionally
THE TUBERCULIDS
Lichen scrofulosorum, erythema induratum, papulo-
necrotic tuberculids, lupus miliaris disseminatus faciei,
TABLE 184-2
29
Tuberculids
Terminology:
Relationship to
Tuberculosis Entities
Tuberculids: conditions Lichen scrofulosorum
in which Mycobacterium Papulonecrotic tuberculid
tuberculosis/bovis appears to
play a significant role
Facultative tuberculids: Nodular vasculitis/erythema
conditions in which M. induratum of Bazin
tuberculosis/bovis may be one Erythema nodosum
Chapter 184
of several pathogenic factors
Nontuberculids: conditions Lupus miliaris disseminatus
formerly designated as faciei
tuberculids; there is no Rosacea-like tuberculid
relationship to tuberculosis Lichenoid tuberculid
::
Tuberculosis and Infections with Atypical Mycobacteria
and other eruptions with rather exotic designations were
originally included in the tuberculids (Table 184-2).
With the sharp decline in incidence and the effec-
tive treatment of tuberculosis in developed countries,
the tuberculids also became rare. However, this does
not apply to areas in which tuberculosis is still com-
mon, and with the recent resurgence of tuberculosis
associated with AIDS in some Western countries, some
tuberculids are also being observed again.
The pathogenic relationship of the tuberculids to
tuberculosis is still poorly understood. Although there
is no doubt that such a relationship exists for some
tuberculids, in other cases it appears highly unlikely.
PCR testing revealed M. tuberculosis DNA in skin
lesions of erythema induratum/nodular vasculitis and
papulonecrotic tuberculid in one series of patients, but
in another, results were uniformly negative.18,19 Thus,
M. tuberculosis infection may be responsible directly or
indirectly for some cases of these diseases but not all,
and the usefulness of lesional PCR testing may vary
among clinical settings. Consistent with this statement,
antituberculosis drugs are beneficial in some cases but
not all; spontaneous involution may occur, and some
patients appear to respond well to other therapies. It
should be noted that, although not considered a tuber-
culid, sarcoidosis has been postulated to result from an
immunologic reaction to mycobacterial antigens.20
The following discussion includes only those condi-
tions for which a preponderance of the evidence sup-
ports a tuberculous etiology (see Table 184-2).
LICHEN SCROFULOSORUM
EPIDEMIOLOGY AND PATHOGENESIS. Lichen
scrofulosorum is an uncommon lichenoid eruption
ascribed to hematogenous spread of Mycobacteria in an
individual strongly sensitive to M. tuberculosis. Usu-
ally associated with chronic tuberculosis of the lymph
nodes, bones, or pleura, it has also been observed after
BCG vaccination and in association with M. avium-
intracellulare infections.21 2233
29 BOX 184-6 DIFFERENTIAL DIAGNOSIS
OF LICHEN SCROFULODERMA
Most Likely
Lichen planus
Lichen nitidus
Consider
Lichenoid secondary syphilis
Micropapular forms of sarcoidosis

Figure 184-9 Papulonecrotic tuberculid on the forearm.

Section 29

CLINICAL FINDINGS. Lesions are usually con-
fined to the trunk and occur most often in children
and adolescents with active tuberculosis. The lesions
are asymptomatic, firm, follicular or perifollicular flat-
topped yellowish or pink papules, sometimes with fine
::
tuberculid is a reaction to particulate tuberculous anti-
gen and, in some cases, to living organisms as well.26
CLINICAL FINDINGS. Sites of predilection are the
extensor aspects of the extremities, buttocks, and lower

scale. Lichenoid grouping is pronounced, and lesions trunk (Fig. 184-9), but the eruption may become wide-
Bacterial Disease

may coalesce to form rough, discoid plaques. Lesions spread. Distribution is symmetric, and consists of dissemi-
persist for months, but spontaneous involution even- nated crops of livid or dusky red papules with a central
tually occurs. Antituberculosis therapy results in com- depression and an adherent crust over a crater-like ulcer.
plete resolution within weeks. There is spontaneous involution, which leaves pitted scars.

HISTOPATHOLOGY. Superficial tuberculoid gran- HISTOPATHOLOGY. Characteristically, a wedge-

ulomas develop around hair follicles or independent
of the adnexa. Mycobacteria are not seen in the sections
and cannot be cultured from biopsy material.
DIFFERENTIAL DIAGNOSIS. (Box 184-6)
PAPULONECROTIC TUBERCULID
EPIDEMIOLOGY. Papulonecrotic tuberculid is a
symmetric eruption of necrotizing papules, appearing
in crops and healing with scar formation that occurs
preferentially in children or young adults. It is rarely
reported but may not be uncommon in populations
with a high prevalence of tuberculosis.
shaped necrotic area in the upper dermis extends into
the epidermis. The inflammatory infiltrate surround-
ing this necrotic area may be nonspecific, but is usu-
ally tuberculoid. Involvement of the blood vessels is
a cardinal feature and consists of an obliterative and
sometimes granulomatous vasculitis leading to throm-
bosis and complete occlusion of the vascular channels.
DIFFERENTIAL DIAGNOSIS. (Box 184-7)
NODULAR VASCULITIS/ERYTHEMA
INDURATUM OF BAZIN
(See Chapter 70)

ETIOLOGY AND PATHOGENESIS. As a rule,

bacteria cannot be demonstrated in lesions. In most ERYTHEMA NODOSUM
cases, the tuberculin test shows a positive reaction, and
associated pulmonary or extrapulmonary tuberculosis (See Chapter 70)
is common. LV has been reported to evolve with papu-
lonecrotic tuberculid. Lesions are reported to respond
promptly to antituberculosis therapy whether or not a BOX 184-7 DIFFERENTIAL DIAGNOSIS
tuberculous focus is identified.
OF PAPULONECROTIC TUBERCULID
In studies of skin lesions in patients with papulone-
crotic tuberculid, M. tuberculosis DNA was detected in Most Likely
approximately 50% of the skin biopsies (11 out of 22 Pityriasis lichenoides et varioliformis acuta
samples).22,23,24 M. kansasii infection was documented Prurigo
in one patient.25
Some cases of papulonecrotic tuberculid have been Consider
associated with discoid lupus erythematosus, arthritis, Lichen urticatus
or erythema nodosum. Although papulonecrotic tuber- Secondary syphilis
culid is classified as an id reaction and therefore, by
Always Rule Out
definition, is not due to direct involvement of the skin
Leukocytoclastic necrotizing vasculitis
by the organism, some of the lesions have been posi-
2234 tive on culture. It seems most likely that papulonecrotic
TREATMENT OF CUTANEOUS
TUBERCULOSIS
In general, the management of cutaneous tuberculosis is
similar to that of tuberculosis of other organs.2730 Che-
motherapy is usually the treatment of choice (Table 184-
3A and eTable 184-3B in online edition), but ancillary
29
measures may be required. Vaccines against M. tuber-
culosis have been attempted,27 but are still not available.
Although they are not yet established as a therapeu-
tic option, cytokines such as interleukin 2, interferon-,

TABLE 184-3A
Therapy Guidelines for Mycobacterium tuberculosis Infections

Rating
Initial Phase Continuation Phase (Evidence)a,b
Range
Interval and Interval and of Total

Chapter 184
Dosesc Dosesc,d Doses
(Minimal (Minimal (Minimal
Regimen Drugs Duration) Regimen Drugs Duration) Duration) HIV HIV+
1 INH 7 days per week for 1a INH/RIF 7 days per week for 184130 (26 A (I) A (II)
RIF 56 doses (8 weeks) or 1b INH/RIF 126 doses (18 weeks) weeks) A (I) A (II)c

::
PZA 5 days per week for 1cf INH/RPT or 5 days per week 9276 (26 B (I) E (I)
EMB 40 doses (8 weeks)e for 90 doses weeks) 7458

Tuberculosis and Infections with Atypical Mycobacteria

(18 weeks)e (26 weeks)
Twice weekly for
36 doses (18 weeks)
Once weekly for
18 doses (18 weeks)
2 INH 7 days per week for 2a 2bf INH/RIF Twice weekly for 36 6258 (26 A (II) B (II)c
RIF 14 doses (2 weeks), INH/RPT doses (18 weeks) weeks) 4440 B (I) E (I)
PZA then twice weekly Once weekly for (26 weeks)
EMB for 12 doses (6 18 doses (18 weeks)
weeks), or 5 days per
week for 10 doses
(2 weeks)e, then
twice weekly for
12 doses (6 weeks)
3 INH Three times weekly 3a INH/RIF Three times weekly 78 (26 weeks) B (I) B (II)
RIF for 24 doses (8 for 54 doses
PZA weeks) (18 weeks)
EMB
4 INH 7 days per week for 4a INH/RIF 7 days per week for 273195 (39 C (I) C (II)
RIF 56 doses (8 weeks) or 4b INH/RIF 217 doses (31 weeks) weeks) C (I) C (II)
EMB 5 days per week for or 5 days per week 118102 (39
40 doses (8 weeks)e for 155 doses weeks)
(31 weeks)e
Twice weekly for 62
doses (31 weeks)
a
Definitions of evidence ratings: A = preferred; B = acceptable alternative; C = offer when A and B cannot be given; E = should never be given.
b
Definitions of evidence ratings: I = randomized clinical trial; II = data from clinical trials that were not randomized or were conducted in other
populations; III = expert opinion.
c
DOT, Directly Observed Therapy. Among patients with extrapulmonary tuberculosis, regimen 1 is recommended as initial therapy unless the
organisms are known or strongly suspected of being resistant to the first-line drugs. If PZA cannot be used in the initial phase (i.e., regimen
4), the continuation phase must be increased to 7 months. Doses of medications (maximum dose) when given daily: INH, isoniazid 5 mg/kg
(300mg); RIF, rifampin 10 mg/kg (600 mg); PZA, pyrazinamide 25 mg/kg (2000 mg); EMB, ethambutol 18 mg/kg (1600 mg); RPT, rifapentine,
which is given once weekly at 10 mg/kg.
When DOT is used, drugs may be given 5 days/week and the necessary number of doses adjusted accordingly. Although there are no studies
that compare five with seven daily doses, extensive experience indicates this would be an effective practice.
d
Patients with cavitation on initial chest radiograph and positive cultures at completion of 2 months of therapy should receive an 8-month
(31-week; either 217 doses [daily] or 62 doses [twice weekly]) continuation phase.
e
Five-day-a-week administration is always given by DOT. Rating for 5 day/week regimens is AIII.
Not recommended for HIV-infected patients with CD4+ cell counts <100 cells/ml.
f
Options 1c and 2b should be used only in HIV-negative patients who have negative sputum smears at the time of completion of 2 months of
therapy and who do not have cavitation on initial chest radiograph. For patients started on this regimen and found to have a positive culture
from the 2-month specimen, treatment should be extended an extra 3 months.
From American Thoracic Society, CDC, and Infectious Disease Society of America: Treatment of tuberculosis. MMWR Recomm Rep 2003; 52:1-77 2235
29 interleukin 12, and granulocyte-macrophage colony-
stimulating factor may help to control intracellular
pathogens and thereby shorten the duration of ther-
apy and overcome drug resistance.31 The immuno-
modulatory drug thalidomide (see Chapter 235) may
prove to be useful in controlling problems related to
the inflammatory response that may follow treatment
of multibacillary infection and could become a useful
adjunctive drug, as it is in the treatment of leprosy.
SPECIAL CONSIDERATIONS IN
TREATING TUBERCULOSIS OF THE SKIN
In contrast to systemic infection, for which triple-drug
Section 29
therapy is recommended, tuberculosis verrucosa cutis
and localized forms of LV without evidence of associ-
ated internal tuberculosis may be treated with isoniazid
alone for up to 12 months. Because viable Mycobacteria
have been found in clinically healed lesions, treatment
::
should be continued for at least 2 months after complete
involution of the lesions. Surgical intervention is quite
Bacterial Disease
helpful in scrofuloderma, because it reduces morbidity
and shortens the required length of chemotherapy. Small
lesions of LV or tuberculosis verrucosa cutis are also best
excised, but tuberculostatics should be given concomi-
tantly. Plastic surgery is important as a corrective mea-
sure in cases of long-standing LV with mutilation.
Extensively drug resistant (XDR) TB is defined as
resistance to at least rifampicin and isoniazid from
among the first line anti-TB drugs (which is the defi-
nition of MDR TB) in addition to resistance to any
fluoroquinolone, and to at least one of the three inject-
able second-line anti-TB drugs used in TB treatment
[(1) capreomycin, (2) kanamycin, and (3) amikacin].
The CDC and WHO have outlined that XDR TB poses
a grave global public health threat and has a higher
risk of death as it renders patients virtually untreatable
with currently available drugs.32
DISEASES CAUSED BY
MYCOBACTERIA OTHER THAN
M. TUBERCULOSIS
MOTT were identified as human pathogens in 1938
(Mycobacterium fortuitum), in 1948 (Mycobacterium ulcer-
ans), and in 1954 (Mycobacterium marinum). However,
overshadowed by the infectious disease burden due to
M. leprae and M. tuberculosis, the pathogenic potential
of slow-growing MOTT species has been recognized
only in recent decades. Because MOTT infections usu-
ally closely mimic infections with M. tuberculosis, and
the bacteria have strict and often unusual requirements
for culture, they are still probably underdiagnosed.
IDENTIFICATION OF MYCOBACTERIA
OTHER THAN M. TUBERCULOSIS
As with other infectious diseases, the diagnosis of
mycobacterial infection depends on the identification
2236 of the microorganism isolated from the host. Speci-
mens for culture should be sent to a special laboratory
DISEASES CAUSED BY MYCOBACTERIA
OTHER THAN M. TUBERCULOSIS AT A
GLANCE
A heterogeneous group of diseases caused
by a variety of obligate or facultatively
pathogenic Mycobacteria other than those of
the Mycobacterium tuberculosis complex.
Involvement depends on the type of
Mycobacterium, the route of infection, and the
immune status of the host.
Various organs may be involved.
Mycobacteria other than M. tuberculosis
(MOTT) are more often the cause of skin
disease than M. tuberculosis.
Diagnosis relies on histopathologic analysis
and the results of culture.
Incidence is unknown, but endemic areas
exist for certain types of MOTT.
Treatment is unlike that of tuberculosis, and
no strict international guidelines have been
developed. Effective antibiotics are known
for each mycobacterial species but should be
checked by sensitivity testing.
familiar with the special growth requirements of these
organisms.
Antigens for intradermal skin testing (PPDs) for
many of the clinically relevant mycobacterial species
have been prepared in analogy to PPD from M. tuber-
culosis, but their accessibility is very limited and they
are therefore little used.
Histopathologic analysis is supportive but cannot
distinguish among mycobacterial species, because all
share similar histopathologic features.33
Treatment is summarized in Table 184-4. Impor-
tantly, some MOTT organisms are resistant to standard
tuberculosis therapy. PCR testing for mycobacterial
DNA is not yet reliable enough to play a role in the
diagnosis of disease but can sometimes be useful in
distinguishing among species.
ETIOLOGY AND PATHOGENESIS. MOTT are
widely distributed in nature and are usually commen-
sals or saprophytes, rather than pathogens. Atypical
Mycobacteria are usually acquired from environmental
sources such as water or soil, and their role in disease
reflects their natural distribution and, possibly, local life-
styles. These organisms are thought to cause mycobac-
terial skin disease more often than does M. tuberculosis.
Cases tend to be sporadic, but certain types of expo-
sures may lead to small community outbreaks.3,34 Any
organ or organ system may be affected (Table 184-5), but
MOTT seem much less likely to disseminate than M.
tuberculosis, and infections usually run a more benign
 TABLE 184-4
29
Treatment of Infections with Mycobacteria Other Than M. tuberculosis
Mycobacterium Species

Intracellulare-
Treatment Ulcerans Marinum Kansasii avium Scrofulaceum Haemophilum Chelonae Fortuitum

Amikacin + + +
Ansamycin +
Azithromycin +
Cefoxitin +
Ciprofloxacin +

Chapter 184
Clarithromycin + + +
Clofazimine + +
Co-trimoxazole +
Cycloserine +

::
Dapsone +

Tuberculosis and Infections with Atypical Mycobacteria

Doxycycline + +
Erythromycin +
Ethambutol a
+ + + +
Ethionamide + +
Imipenem +
Isoniazid + + +
Kanamycin +
Minocycline + + + + +b
Rifampicin + + + + +
Rifamycin + + +
Streptomycin a
+ + +
Tobramycin +
Surgery + + + +
a
Usual antituberculosis drugs.
b
Alone or in combination with ciprofloxacin or rifampicin.

TABLE 184-5
Organ Involvement in Infections with Atypical Mycobacteria

Organ Involvement

Mycobacterial Species Skin, Subcutis Lymph Nodes, Other Organs

Mycobacterium tuberculosis/bovis complex (including + +
Mycobacterium africanum and Bacille Calmette-Gurin)
Mycobacterium marinum +
Mycobacterium ulcerans +
Mycobacterium gordonae +
Mycobacterium haemophilum +
Mycobacterium kansasii + +
Mycobacterium avium-intracellulare complex (including + +
Mycobacterium scrofulaceum)
Fast growers: Mycobacterium fortuitum, Mycobacterium + 2237
chelonae, Mycobacterium abscessus
29
Section 29
::
Bacterial Disease
Figure 184-10 Verrucous plaque of spam disease on the
knee of a Pacific Islander patient. (Used with permission
from Dr. Joseph Lillis.)
and limited course. As a rule, MOTT are much less
responsive to antituberculosis drugs but may be sensi-
tive to other chemotherapeutic agents.
Only two organisms, M. ulcerans and M. marinum,
produce a characteristic clinical picture. An immuno-
suppressed state of the host or damage to a particular
organ (e.g., in M. kansasii infection of the lung) facili-
tates these infections.
New mycobacterial pathogens are described from
time to time, which suggests that their full pathogenic
potential is not yet appreciated. Recently, an outbreak
of skin disease caused by a nontuberculous Mycobac-
teria in Pacific Islanders from Satowan was reported
in the literature.35 These patients presented with long-
standing verrucous and keloidal plaques (locally
known as spam disease) (Fig. 184-10). Histopatho-
logical and PCR data demonstrated a nontuberculous
mycobacterial infection as the cause.
SKIN INFECTIONS WITH
MYCOBACTERIA OTHER THAN
M. TUBERCULOSIS
MYCOBACTERIUM ULCERANS (BURULI ULCER
DISEASE). The natural habitat of M. ulcerans is still not
known, and it has never been found outside the human
body, but M. ulcerans infection occurs in wet, marshy, or
swampy areas and seems to have to do with contami-
nated water. M. ulcerans is the third most frequent myco-
bacterial pathogen, after M. tuberculosis and M. leprae.
Clinical Findings. The disease is found most often
in children and young adults, and affects females
2238 more often than males. A subcutaneous nodule gradu-
Figure 184-11 Mycobacterium ulcerans infection in a
child in Uganda. The knee bears an ulcer with an infiltrated
undermined margin and a base of necrotic adipose and
connective tissue. (Used with permission from M. Dietrich,
MD.)
ally enlarges and eventually ulcerates. A blister may
develop before ulceration. The ulcer is deeply under-
mined, and necrotic fat is exposed (Fig. 184-11). The
preceding nodule as well as the ulcer is painless, and
the patient continues to feel well. The painless nature
of the ulcer has been attributed to nerve damage and
tissue destruction caused by the toxin mycolactone.
The lesions may occur anywhere on the body but tend
to be limited to the extremities in adults. They may
be large, involving a whole limb. The ulceration may
persist for months and years, and healing and progres-
sion of the ulceration may occur in the same patient.
This process may lead to appreciable and sometimes
disabling scarring and lymphedema. Neither lymph-
adenopathy nor any constitutional signs appear at any
time unless the disease process is complicated by bac-
terial superinfection.
Differential Diagnosis. (Box 184-8)
MYCOBACTERIUM MARINUM (MYCOBACTE-
RIUM BALNEI, FISHTANK/SWIMMING POOL
GRANULOMA). M. marinum occurs in freshwater
and saltwater, including swimming pools and fish
tanks.
Clinical Findings. Risk factors for M. marinum
infection are a history of trauma and water- or fish/
seafood-related hobbies and occupations. The disease
begins as a violaceous papule at the site of a trauma
23 weeks after inoculation. Patients may have a nod-
ule or a psoriasiform or verrucous plaque at the site of
inoculation, usually the hands, feet, elbows, or knees
(Fig. 184-12). The lesions may ulcerate. Usually, the
 BOX 184-8 DIFFERENTIAL DIAGNOSIS BOX 184-9 DIFFERENTIAL DIAGNOSIS
29
OF MYCOBACTERIUM ULCERANS LESIONS OF MYCOBACTERIUM MARINUM LESIONS
EARLY LESIONS LATE LESIONS Most Likely
Blastomycosis
Most Likely
Coccidioidomycosis
Foreign body Blastomycosis or Sporotrichosis
granuloma other deep fungus
Consider
Sebaceous cyst infection
Histoplasmosis
Pyoderma
Nocardiosis
gangrenosum
Tertiary syphilis
Consider Yaws

Chapter 184
Phycomycosis Suppurative Always Rule Out
Nodular fasciitis panniculitis Other mycobacterial infections
Appendageal tumor
Always Rule Out
Panniculitis Necrotizing cellulitis

::
Nodular vasculitis M. kansasii usually occurs in adults, and is more com-

Tuberculosis and Infections with Atypical Mycobacteria

lesions are solitary, but occasionally lymphocutaneous
spread occurs. They may heal spontaneously within 12
years, with residual scarring. Occasionally, the lesions
are suppurative, rather than granulomatous, and may
be multiple in both normal or immunosuppressed hosts.
Differential Diagnosis. (Box 184-9)
MYCOBACTERIUM KANSASII . M. kansasii is the
atypical Mycobacterium most closely related to M. tuber-
culosis. It is usually acquired from the environment.
Endemic areas include Texas, Louisiana, the Chicago
area, California, and Japan. Skin disease caused by
mon in individuals with underlying immunosuppres-
sion caused by Hodgkin disease, treatment for organ
transplantation, or AIDS. Inoculation is usually attrib-
utable to minor trauma such as a puncture wound.
Clinical Findings. M. kansasii infection may pres-
ent in several forms. Most frequently, there are papules
in a sporotrichoid distribution. Sometimes, subcutane-
ous nodules extend to deeper structures and may result
in a carpal tunnel syndrome or joint disease. An ulcer-
ated plaque may also develop as a metastatic lesion.
Disseminated disease caused by M. kansasii infec-
tion occurs in immunosuppressed patients, and such
patients have cellulitis and abscesses rather than gran-
ulomatous lesions. The most commonly affected organ
is the lung, usually in patients with other pulmonary

A B

Figure 184-12 A. Mycobacterium marinum infection on the back of the hand. Granulomatous nodular lesion with central ul-
ceration at the site of inoculation. (Used with permission from A. Kuhlwein, MD.) B. Verrucous, violaceous plaque with central
spontaneous clearing occurring at the site of an abrasion sustained in a fish tank. The lesion was caused by M. marinum. 2239
29 BOX 184-10 DIFFERENTIAL DIAGNOSIS
OF MYCOBACTERIUM KANSASII LESIONS
Most Likely
Sporotrichosis
Consider
Tuberculosis
Always Rule Out
Other granulomatous infections of the skin
Section 29
conditions (silicosis, emphysema). Infection may also
cause cervical lymphadenopathy. As with M. tubercu-
losis, M. kansasii present in nasopharyngeal secretions
can lead to periorificial cutaneous infection. These
infections usually progress slowly, although a chronic
::
stable lesion or even spontaneous regression may
Bacterial Disease
occur. Drug therapy should be initiated as soon as the
diagnosis is made.
Differential Diagnosis. (Box 184-10)
MYCOBACTERIUM SCROFULACEUM. Mycobac-
terium scrofulaceum is widely distributed in the envi-
ronment.
Clinical Findings. The usual manifestation of
M. scrofulaceum infection is cervical lymphadenitis, fre-
quently unilateral, in children, mainly between the ages
of 1 and 3 years. Submandibular and submaxillary nodes
are typically involved, rather than the tonsillar and ante-
rior cervical nodes, as is characteristic for M. tuberculosis
infection. There are no constitutional symptoms. Involved
lymph nodes enlarge slowly over several weeks, and
eventually ulcerate and develop fistulae. There is rarely
an evidence of lung or other organ involvement. In most
cases, the disease is benign and self-limited.
Differential Diagnosis. The differential diagno-
sis includes other forms of bacterial lymphadenitis;
viral infections, including mumps and mononucleosis;
and malignancy, including solid tumors, lymphoma,
and leukemia.
MYCOBACTERIUM AVIUM-INTRACELLULARE.
M. avium-intracellulare encompasses organisms with a
wide variety of microbiologic and pathogenic proper-
ties. Well over 20 subtypes can be separated by immu-
nologic techniques, although this is not necessary for
clinical purposes.
These organisms are usually grouped together with
M. scrofulaceum in the so-called M. avium-intracellu-
lare-scrofulaceum complex, but are separated here for
clinical reasons. Whereas M. scrofulaceum produces
only a benign, self-limited lymphadenopathy with no
organ involvement, M. avium-intracellulare infection
usually causes lung disease or, less frequently, osteo-
myelitis. It may also produce a cervical lymphadenitis
with sinus formation that is clinically indistinguish-
2240 able from tuberculous scrofuloderma.
Clinical Findings. Primary skin disease caused
by M. avium-intracellulare has been reported in rare
instances, presenting as single or multiple painless,
scaly yellowish plaques, sometimes resembling LV, or
as subcutaneous nodules with a tendency to ulceration
and a slowly progressive, chronic course. Sometimes,
skin involvement occurs secondary to disseminated
infection with M. avium-intracellulare. Skin lesions
have included generalized cutaneous ulcerations,
granulomas, infiltrated erythematous lesions on the
extremities, pustules, and soft-tissue swelling. M.
avium-intracellulare infections are an important cause
of morbidity in patients with AIDS (see Chapter 198).
MYCOBACTERIUM SZULGAI, MYCOBACTE-
RIUM HAEMOPHILUM, MYCOBACTERIUM
GENAVENSE. Mycobacterium szulgai, Mycobacte-
rium haemophilum, and M. genavense are rarely found
to cause human disease in cases of otherwise unex-
plained cervical lymphadenitis, cellulitis, draining
nodules and plaques, bursitis, pneumonia, and subcu-
taneous granulomatous eruptions.
MYCOBACTERIUM FORTUITUM, MYCO-
BACTERIUM CHELONAE, MYCOBACTERIUM
ABSCESSUS. M. fortuitum, Mycobacterium chelonae,
and Mycobacterium abscessusthree species of fast-
growing, facultative pathogenic Mycobacteriawere
previously grouped in the M. fortuitum complex but
are now recognized as distinct species. These organ-
isms seem to be widely distributed and can commonly
be found in soil and water. Contamination of various
materials, including surgical supplies, occurs but does
not always result in clinical disease.
Clinical Findings. M. fortuitum, M. chelonae, and
M. abscessus cause similar clinical diseases. Infection
usually follows a puncture wound or a surgical pro-
cedure. The disease manifests itself as a painful red
infiltrate at the site of inoculation; there are no signs of
dissemination and no constitutional symptoms. Cold
postinjection abscesses, especially in the tropics, may
also be caused by fast-growing Mycobacteria. Recent
cases in the United States have followed after pedi-
cures and water immersion in salons.
The lesion is a dark red nodule, often with abscess
formation and clear fluid drainage. Healthy children
and adults may become infected, but disseminated dis-
ease usually occurs in hemodialysis patients or other
immunologically compromised individuals. The dis-
ease course consists of multiple recurrent episodes of
abscesses on the extremities or a generalized macular
and papular eruption. Internal organs may be involved.
Histopathology. There is simultaneous occurrence
of polymorphonuclear leukocyte microabscesses and
granuloma formation with foreign body-type giant cells,
the so-called dimorphic inflammatory response. There
is usually necrosis but no caseation. Acid-fast bacilli
may occasionally be found within microabscesses.
Diagnosis. Organisms of the M. fortuitum complex
may be identified by special laboratories to permit a
rational treatment.