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5.3 Bacterial Infections
■
Most commonly affects immunosuppressed (esp.
kidney transplant patients)
■
Most commonly affects GU tract; may affect skin of
perianal/genital region (ulcerated abscesses and soft
polypoid lesions)
■
Histology: dense granulomatous inltrate composed of
von Hansemann cells (large macrophages w/
eosinophilic cytoplasm [Michaelis-Gutmann bodies];
stain w/ CD68, lysozyme, a-1 antitrypsin)
Michaelis-Gutmann bodies: round, laminated,
calcied basophilic intracytoplasmic inclusions;
comprised of incompletely killed bacteria within
calcied phagolysosomes; stain w/ von Kossa, PAS,
Perls, Giemsa)
■
Treatment:
Localized: surgical excision
Nonsurgical candidates: difcult to treat; may try
long courses of ciprooxacin, TMP-SMX, or
clofazimine
• Tularemia (rabbit fever and deer y fever)
■
Gram-negative coccobacillus, Francisella tularensis
■
Mode of transmission 5 contact w/ rabbit carcasses
(classic!), deer ies, and ticks; increased risk in hunters
and animal handlers
■
Most common presentation is ulceroglandular 5 80%
(. pneumonic . glandular, typhoidal .
oropharyngeal . oculoglandular), which p/w necrotic,
punched-out ulcer at inoculation site w/ suppurative
LAD (Box 5.2)
■
Treatment: streptomycin (treatment of choice)
• H. inuenzae cellulitis
■
Gram-negative coccobacillus
■
Classically affects infants, p/w deep red violaceous/
blue facial cellulitis (most commonly periorbital or
buccal) following an upper respiratory infection-like
illness
■
Usually positive blood cultures
■
Treatment: third-generation CSN
■
Incidence has decreased since development of Hib
vaccine
• Rhinoscleroma
■
Chronic granulomatous infection of nose and upper
respiratory tract
■
Affects adults, mainly in tropical locations
■
Transmitted by inhalation of Klebsiella rhinoscleromatis
■
a/w Cellular immune defects: inability of macrophages
to kill phagocytosed bacteria n Mikulicz cells (large,
vacuolated histiocytes containing bacteria)
■
Three clinical phases:
Catarrhal phase (rhinitis, obstruction from soft
tissue edema)
Granulomatous/inltrative phase (granulomatous
nodules in nose/upper respiratory tract, epistaxis,
dysphonia, anesthesia of soft palate, and Hebra nose)
Box 5.2 Differential Diagnosis of Ulceroglandular Diseases Mnemonic
“My Aunt’s Temperamental Tall Rats Plague Glands”
Melioidosis, Anthrax, Tularemia, TB chancre, Rat-bite fever, Plague,
Glanders
Sclerotic phase (extensive scarring requires
tracheotomy and nasal reconstruction)
■
Histology: dense pan-dermal inltrate of Mikulicz cells
containing bacteria (seen w/ Warthin-Starry, Giemsa)
and Russell bodies
■
Treatment: tetracycline (treatment of choice) for
6 months along with surgical correction of airway;
ciprooxacin is second line
• Salmonellosis (typhoid fever)
■
Enteric infection caused by Salmonella typhi
■
Spread by direct contact w/ infected individuals or
carriers
■
p/w Fever, nausea/vomiting, diarrhea, headache, and
characteristic “rose spots” of skin (2- to 8-mm pink,
grouped papules on trunk); bacteria can be cultured
from rose spots
■
Treatment: quinolones (treatment of choice); use
third-generation CSN in children
• Rat-bite fever (“Haverhill fever”)
■
Streptobacillus moniliformis
■
As a result of a rat bite (“rat-bite fever”), or occasionally,
ingestion of contaminated food (“Haverhill fever”); h
incidence in urban areas w/ high rat concentration
■
Classic triad (paroxysmal fever, migratory polyarthritis,
and acral rash)
p/w Redness, edema, and ulceration at bite site (w/
LAD) n paroxysmal fever w/ systemic symptoms n
2 to 4 days later, migratory polyarthritis 1 acral
eruption (palms and soles most common) of
petechial red macules/papules, vesicles, or pustules
Up to 15% mortality
■
Treatment: PCN (treatment of choice) for 1 week
(6 weeks if septicemic)
• Plague
■
Caused by Yersinia pestis, a Gram-negative bipolar
bacillus
Characteristic “safety pin” appearance of bacteria
on Gram or Giemsa stain
■
Reservoir 5 rodents; usually transmitted to humans by
ea bites (.rodent contact, inhalation)
■
Forms:
Bubonic (most common): pustule or ulcer at
inoculation site (10%) 1 painful, suppurative
regional LAD 5 “buboes” (groin, axillae most
common); 50% mortality rate if untreated
Septicemic: vesiculopustular eruption w/ petechiae,
purpura; hemorrhagic and necrotic lesions in
nasopharyngeal and GI tracts; 100% mortality if
untreated
Pneumonic: acute pneumonitis; 100% mortality if
untreated
■
Treatment:
First line: aminoglycosides (streptomycin and
gentamicin)
Plague meningoencephalitis: chloramphenicol
Postexposure prophylaxis: doxycycline or
ciprooxacin 3 7 days
• Vibrio vulnicus
■
Most commonly affects men . 40 years old who have
predisposing factors: liver disease (hemochromatosis,
cirrhosis, or alcoholism), diabetes (peripheral
315
CHAPTER 5 • Infectious Diseases
neuropathy/vasculopathy predisposes to wound
infections), GI disease (peptic ulcer disease w/
antacids), immunosuppression, and end-stage renal
disease
■
Reservoir 5 shellsh
■
Two modes of infection:
Cutaneous exposure to contaminated seawater/
shellsh: affects shellsh handlers; trauma n
painful cellulitis n hemorrhagic bullae n may
progress to NF, myositis, or septicemia
Consumption of raw/undercooked shellsh: most
commonly from raw oysters; septicemia, abdominal
cramps, and hypotension; 75% have skin ndings—
red-purple macules/vesicles n progress to
hemorrhagic bullae and necrotic plaques
■
Treatment: doxycycline 1 third-generation CSN
• Bite-induced infections
■
Dog bites are most common (.cats .humans);
human bites are most likely to get infected
Dog bite: Pasteurella multocida, Pasteurella canis, or
Capnocytophaga canimorsus (potentially fatal in
asplenic or immunosuppressed patients)
Cat bite: P. multocida . Streptococcal spp.
Human bite: Eikenella corrodens (a/w chronic
infections), S. aureus (a/w severe infections),
Peptostreptococcus, Enterococcus, and Bacteroides
■
Treatment:
Amoxicillin/clavulanate (treatment of choice)
Also important to irrigate the wound and give
tetanus vaccine
III. Nonvenereal spirochete infections
Borrelia
• Lyme disease
■
Agent: Borrelia burgdorferi (#1 in the United States);
Borrelia garinii and Borrelia afzelii (#1 in Europe)
■
Reservoir: white-tailed deer and white-footed mouse
■
Vector: Ixodes spp. (hard body) ticks; specic type varies
by geographic region:
Ixodes scapularis (Ixodes dammini) n #1 cause in
the United States (prevalent in Eastern United States
and Great Lakes region)
Ixodes pacicus n the Western United States
Ixodes ricinus n Europe, Ixodes persulcatus nAsia
■
Pathogenesis: Ixodes tick feeds on infected animal
reservoir n spirochetes stored in tick’s salivary glands
n tick bites human and releases Borrelia spirochetes
into dermis n erythema migrans develops at bite site 1
to 2 weeks later n if untreated, hematogenous
dissemination 1 systemic symptoms
■
Three clinical stages of Lyme disease:
Early localized:
♦ Erythema migrans (90%): initial cutaneous
manifestation; develops 7 to 14 days post-tick
attachment; p/w expanding annular plaque w/
central clearing (“bull’s eye” appearance) n
reaches . 5 cm diameter; favors trunk (#1 site in
children), legs (#1 site in adults), and intertriginous
areas; lesion self-resolves in 4 weeks if untreated
♦ Disseminated erythema migrans lesions
(25%–50%): multiple smaller annular lesions;
arise days to weeks after primary erythema
migrans lesion
♦ Other: nonspecic u-like symptoms and
regional LAD
Early disseminated: as a result of hematogenous
spread of spirochetes; arises if initial phase untreated
♦ Borrelial lymphocytoma (1%, Europe only):
strongly a/w B. afzelii and B. garinii; p/w rm,
plum-colored tender nodule/plaque on earlobes
(children), or nipple/areola (adults)
♦ Arthritis (60%): mono/oligo-articular (knee 5
most common site); arises weeks to months after
initial infection
♦ Neurologic abnormalities (10%): most commonly
Bell’s palsy
♦ Cardiac complications (5%): AV block,
myopericarditis
Chronic:
♦ Acrodermatitis chronica atrophicans (10%,
Europe only): strongly a/w B. afzelii and B.
garinii; occurs months to years after initial
infection in middle-aged women; two clinical
phases: erythematous plaques with “doughy”/
swollen skin on distal extremities (early phase;
easily treated/reversible) n progresses to atrophic
“cigarette-paper” skin w/ telangiectasias (chronic
phase; recalcitrant to treatment) and
subcutaneous brous nodules overlying joints
♦ Other: encephalopathy, neuropathy, and chronic
arthritis
■
Diagnosis:
Recognition of erythema migrans rash 5 most
sensitive way to conrm Lyme!
Serologic evidence of Lyme infection is often
lacking early (only 41% positive at 1 to 2 weeks,
and 88% positive when checked . 2 weeks into
infection) n cannot rule out Lyme via negative
serologies early in disease course!
Tissue PCR/culture: specic, but not sensitive
Treatment discussed in Table 5.8
■
Other high-yield facts:
Peak incidence in summer (80% of cases in the
United States arise between June and August)
Tick must be attached for . 24 hours to transmit
Lyme n hhh risk if . 48 hours of attachment
Frequent coinfection with Lyme 1 Babesiosis 1
human granulocytic anaplasmosis (HGA) n
doxycycline covers all three agents
European Lyme disease has: larger erythema
migrans lesions that persist longer, g arthritis, and
hh neurologic sequelae
• Other borrelial infections (see Table 5.8)
Nonvenereal (endemic) treponematoses
• Yaws, pinta, and endemic syphilis (bejel) are all caused by
Treponema pallidum subspecies that are morphologically
and antigenically identical to the organism responsible for
venereal syphilis
316
5.3 Bacterial Infections
Table 5.8 Borrelia Infections
Disease Agent Vector Clinical Features Prescription
Lyme disease Borrelia burgdorferi Ixodes dammini (Northeast United
Borrelial lymphocytoma
Acrodermatitis chronica
atrophicans
Louse-borne relapsing
fever (Africa)
Tick-borne relapsing
fever (Western United
States)
Table 5.9 Nonvenereal Treponematoses
Disease (bacterium)
Yaws (T. pallidum
pertenue)
Pinta (T. pallidum
carateum)
Endemic
syphilis/“bejel” (T.
pallidum endemicum)
B. afzelli .B. garinii
B. afzelli .B. garinii
B. recurrentis Pediculus humanus var. corporis
B. duttonii
B. hermsii
Most Common Age and
Geographic Location Clinicopathologic Features Other High-Yield Facts
Age: children , 15 years old
Location: warm, humid, and
tropical climates (Africa,
Asia, Central and South
America, and Pacic
Islands)
Age: all ages equally affected
Location: Western hemisphere
only (Central and South
America)
Age: children , 15 years old
Location: dry, warm climates
(North Africa and Southeast
Asia)
States and Great Lakes area)
Ixodes pacificus (Western United
States)
Ixodes ricinus (Europe)
I. ricinus (Europe) As previously discussed in text Doxycycline
I. ricinus (Europe) As previously discussed in text Doxycycline
(human body louse)
Ornithodoros (soft-bodied ticks) Like Louse-borne relapsing
1° stage: legs most commonly affected; p/w indurated, red,
painless papule(s) that enlarges to 1–5 cm, then ulcerates
(“Mother Yaw”); occurs at site of inoculation; lower extremities
most common; histology shows spongiosis, acanthosis/
papillomatosis w/ dermal plasma cell inltrate
2° stage: multiple, smaller, symmetrical, widespread eruption w/
“daughter yaws” (smaller “mother yaws” vs. “miniature yaws”
(rm pink papules); face and intertriginous most common;
hyperkeratotic plaques on soles (“crab yaws”); osteoperiostitis,
polydactylitis, periosteal thickening
3° stage: necrotic and ulcerative abscesses that heal with
severe/deforming scars; palmoplantar keratoderma; bony
damage (periostitis, osteitis, osteomyelitis)
Skin-only disease
1° stage: legs most commonly affected; p/w papules surrounded
by red halo; enlarges over months up to .10 cm plaques
2° stage: smaller scaly papules and psoriasiform plaques erupt
(“pintids”) and change in color from red n blue n brown
n gray/black
3° stage: symmetric vitiligo-like lesions over bony prominences
w/ atrophic epidermis; palmoplantar hyperkeratosis; histology
shows lichenoid interface 1 complete loss of melanin 1
epidermal atrophy
1° stage: rarely noticed; p/w inconspicuous papule or ulcer in
mouth or on nipples of breastfeeding women ; may have
hypomelanotic macules on extremities, genitalia, areolae, and
trunk
2° stage: mucous membrane lesions (mucosal patches,
condyloma lata, and angular stomatitis) 1 generalized lymphadenopathy 1 laryngitis 1/– skin lesions
3° stage: Gumma formation of mucous membranes (nasophar-
ynx), skin, cartilage and bones (exostosis, periostitis of tibia/
bula; palate/nasal septum affected)
As previously discussed in text First line: doxycycline
3–4 relapses of paroxysmal
fevers w/ nonspecific flu-like
symptoms and nonspecific
macular or petechial eruption;
more severe than tick form
fever, but only 1–2 relapses
and less severe
In pregnancy or children
,8 years old
is treatment of choice
Doxycycline
Doxycycline
3° stage only occurs in 10%
Mnemonic: “Yaws 5 Jaws”
(big, destructive “bites” are
taken out of affected skin
and bone)
Mnemonic: “Pinta only
paints the skin different
colors”
Mnemonic: “Pinta is a
Spanish word n limited to
Spanish America”
Mnemonic: “similar to
venereal syphilis, but
mucosal disease
predominates over skin”
or “ENDemic syphilis
attacks ENside surfaces”
n amoxicillin
• All three diseases have primary, secondary, and tertiary
stages (Table 5.9)
• Route of transmission: skin, mucous membrane, or fomite
contact
• All except pinta most commonly affect children
• All except bejel most commonly begin on legs
• Serologic assays used for venereal syphilis are also positive
in these diseases, but cannot differentiate between them
■
Treponemal tests (FTA-ABS, MHA-TP, and TPHA): specic
for treponemal infections, may remain positive for life
■
Non-treponemal tests (RPR and VDRL): less specic,
but useful for identifying current or recent infections, or
317
CHAPTER 5 • Infectious Diseases
monitoring response (four-fold decrease 5 successful
treatment; four-fold increase 5 reinfection/relapse)
• Histology for all three resembles venereal syphilis
• Treatment: benzathine PCN (treatment of choice for all)
IV. Sexually transmitted bacterial
infections
Syphilis
• Agent: T. pallidum (Gram-negative spirochete)
• Congenital syphilis
■
Early congenital (,2 years old): snufes, perioral
ssures, dactylitis, Parrot’s pseudoparalysis, syphilitic
pneumonitis, epiphysitis, marasmic syphilis,
pemphigus syphiliticus, and hepatitis
■
Late congenital (.2 years old): keratitis, mulberry
molars, Hutchinson’s teeth (notched/peg-shaped
incisors), rhagades (linear scars at angles of mouth),
saddle nose, Higoumenakis syndrome, Clutton’s joints,
optic atrophy, corneal opacities, and eighth nerve deafness
• Primary (10- to 90-day incubation [avg. 5 3 weeks] until
chancre)
■
Chancre (painless, well-dened, and indurated ulcer)
w/ enlarged lymph nodes
• Secondary (3–10 weeks postchancre; dissemination to
other tissues; clears in 3–12 weeks, but relapses in 25%)
■
Prodromal signs (e.g., malaise, fever, lymph node
enlargement, conjunctivitis, hepatosplenomegaly
[HSM], arthralgia)
■
Papulosquamous/maculopapular generalized, nonitchy, rash (“copper-colored”) w/ papules/plaques on
palms/soles (Fig. 5.11), annular plaques of face
■
“Moth eaten” alopecia
■
Split papules (syphilitic perlèche)
■
Mucous patches in oropharynx (condyloma lata-like
lesions of the mouth)
■
Hypopigmented macules on neck (“necklace of Venus”)
■
Condyloma lata (analogous to “plaques muqueuses” in
oropharynx)
■
HIV patients may have multiple chancres, palmoplantar
keratoderma, lues maligna (fever/arthralgia/headache n
papules/pustules/nodules w/ necrosis/crusting/ulceration)
• Tertiary (months to years after secondary in one third of
untreated patients—the period in between is called
latency and two third of untreated patients stay latent
indenitely)
■
Gummas (skin, bones, liver, and organs)
■
Cardiovascular syphilis (e.g., aortitis)—25%
■
Neurosyphilis (e.g., paresis, dementia, meningitis,
ataxia, tabes dorsalis, optic atrophy, gummas, and
Argyll Robertson pupil (accommodates to light, but
does not react)—25%
• Treatment: IM benzathine PCN (2.4 M IU 3 1 dose for
primary/secondary/early latent disease; 7.2 M IU total for
late latent disease and cardiovascular/gummatous),
aqueous PCN G 18 to 24 M IU daily 3 10 to 14 days—
neurosyphilis/ocular
■
Doxycycline can be used in allergic patients
• Other high-yield facts:
■
M . F, h in MSM
■
h Risk of coinfection w/ HIV (any disease that n
genital ulcers will increase HIV risk)
■
HIV n h risk of neurosyphilis
■
Serologic studies are divided into treponemal (FTAABS, MHA-TP, FTA-ABS-19S-IgM, SPHA) and non-
treponemal (RPR, VDRL; IgG/IgM to cardiolipin); FTAABS and MHA-TP more sensitive/specic, used mainly
to conrm positive non-treponemal tests
■
RPR and VDRL: rst serologic test to become positive
(within 1–2 weeks vs. after third week for treponemal
tests); used to monitor response to therapy as titers
decrease and then become negative after successful
treatment (vs. treponemal tests, which remain positive
throughout life); higher false-positive rate than
treponemal tests (esp. pregnancy and systemic lupus
erythematosus)
■
Warthin-Starry stain identies spirochetes
■
Positive darkeld examination (overall most sensitive
and specic test for diagnosis of primary syphilis, but
operator-dependent)
■
Perform lumbar puncture for CSF examination in
secondary patients with ocular/neurologic symptoms
and all tertiary patients
■
Histology of secondary syphilis: slender, elongated
psoriasiform epidermal hyperplasia 1 lichenoid interface
changes 1 “dirty” dermal inammatory inltrate
(neutrophils, cell debris, and abundant plasma cells)
Fig. 5.11 Secondary syphilis. A classic presentation for secondary syphilis with
copper-colored scaly plaques on the palms and soles. (From Dinulos JGH. Sexually
transmitted bacterial infections. In: Habif’s Clinical Dermatology: A Color Guide to
Diagnosis and Therapy. 7th ed. Philadelphia: Elsevier; 2021:376–412.)
318
Other bacterial venereal diseases
(Table 5.10)
V. Mycobacterial infections
Cutaneous tuberculosis
• Mycobacterium tuberculosis 5 acid-fast, alcohol-fast, aerobic
bacillus, and h risk in HIV
5.3 Bacterial Infections
Table 5.10 Venereal Diseases Other Than Syphilis
Disease Organism Dermatologic Signs Treatment Interesting Facts
Chancroid Hemophilus ducreyi
Gonorrhea Neisseria gonorrhoeae
Lymphogranuloma
venereum
Granuloma
inguinale
(Gram-negative
coccobacilli)
(Gram-negative
diplococci)
Chlamydia trachomatis
(serotypes L1–3)
Klebsiella granulomatis
(intracellular Gramnegative bacillus)
Painful, purulent ulcers with ragged/
undermined borders and brinous base
(may get “kissing ulcers” from apposition
of skin with initial ulcer)
Prepuce/coronal sulcus/frenulum are
common sites
Painful, inguinal, typically unilateral,
lymphadenitis (40%)
Most findings are not cutaneous, but
can get hemorrhagic acral pustules
w/arthritis (of larger joints), and fever
(arthritis-dermatosis syndrome) if
hematogenous dissemination occurs
(more common in menstruation and
C5–9 complement deficiencies)
Stage 1 (after 3–12 days of incubation
period): painless ulcer which resolves
(transient) 1/– lymphangitis
Stage 2 (10–30 days, up to 6 months
after stage 1): buboes (unilateral,
painful, erythematous, and enlarged
inguinal lymph nodes) w/ “groove
sign” (enlarged nodes above and below
Poupart ligament); buboes may rupture
n pus drainage and sinus tracts
Stage 3 (months-years after stage 2;
aka ano-genito-rectal syndrome):
proctocolitis w/ perirectal abscesses,
fistulas, strictures/stenoses, and
“lymphorrhoids” (perirectal/intestinal
lymphatic hyperplasia)
Enlarging chronic painless ulcer with
“beefy red,” friable, hypertrophic
granulation tissue (avg. incubation 5
17 days)
Get “pseudobuboes” (nodules), genital
swelling, and secondary infections (n
bad odor)
Most common sites: prepuce/glans/
frenulum/coronal sulcus (men); vulvar
area (women)
May get extragenital lesions as a result of
dissemination or autoinoculation (skin,
bones, oral, and abdominal)
Azithromycin 1 g PO 3
1 dose (ceftriaxone,
ciprofloxacin are
alternatives)
Dual therapy: Ceftriaxone
250 mg IM 3 1 dose 1
Azithromycin 1 g PO 3
1 dose
Doxycycline 100 mg
PO BID 3 21 days
Azithromycin 1 g PO
once weekly (or 500 mg
daily) for at least 3 weeks
AND until all lesions have
resolved
“School of sh” sign on
Giemsa stain of exudate
smear
M . F; prostitutes are major
reservoir
More common in Africa and
Asia
F . M
Culture is gold standard for
diagnosis and susceptibility
testing (Thayer-Martin
media is used)
Often see coinfection
w/ chlamydia
“Gamna-Favre bodies” in
macrophages on Giemsa
stain
More common in Asia, Africa,
and South America
M . F
“Safety pin” Donovan
bodies on Wright or
Giemsa stain of smears
More common in Papua
New Guinea, Australia, and
South Africa
• Diagnosis made with tuberculin skin test versus
interferon-γ release assays (QuantiFERON Gold)
■
Skin test better in children; interferon-γ test better for
patients who have had BCG (live, attenuated Mycobacterium
bovis) vaccination (false-positive with skin test)
• Inoculation-induced
■
Tuberculous chancre: in patients w/o previous infection
(hence no immunity against TB); 2- to 4-week
inoculation period; painless, red, and indurated papule
that ulcerates—heals # 12 months; may spread to
lymph nodes
■
TB verruca cutis: reinfection via inoculation, in
patients w/ previous infection w/ moderate to high
immunity; #1 form of cutaneous TB; warty/verrucous,
growing papule may heal over years
• Spread of endogenous infection
■
Lupus vulgaris: contiguous spread or hematogenous/
lymphatic; red-brown, sometimes annular, papules/plaques
(with “apple jelly” color on diascopy) that n scarring
centrally; head/neck #1 site; moderate to high immunity
(Fig. 5.12)
■
Scrofuloderma: result of contiguous spread of
infection to skin from underlying disease (usually
cervical lymph nodes and bones); uctuant nodules
that develop sinus tracts, draining to skin, with tethered
appearance; low immunity
■
Oricial TB: patients with advanced TB and poor cellmediated immunity; autoinoculation of mucosa/skin
close to anatomic orice draining active systemic TB
infection n ulceration/drainage
■
Acute miliary TB: hematogenous dissemination from
lung, most often in immunosuppressed patients;
pinpoint blue-red crusty papules n small scars
■
Tuberculous gumma: hematogenous dissemination n
deep nodule that ulcerates/drains; immunosuppressed
patients
319
CHAPTER 5 • Infectious Diseases
Fig. 5.12 Lupus vulgaris: a perioral annular plaque with a papulomatous border
and signs of central clearing in a male patient with pulmonary tuberculosis. (From
the collection of Jan and Titia Warndorff, Department of Dermatology, Amsterdam UMC, Amsterdam, The Netherlands.)
Fig. 5.13 Tuberculoid leprosy. Sharply dened plaque with a raised border and
an absence of hair. (Courtesy, Dr. Omar Lupi. From Tyring SK, Lupi O, Hengge
UR. Mycobacteria. In: Tropical Dermatology. 2nd ed. Philadelphia: Elsevier;
2017:252–279.)
• First-line combination therapy for TB: rifampin,
isoniazid, pyrazinamide, and ethambutol; isoniazid
and/or rifampin can be used in latent infection
Leprosy (Hansen’s disease)
• Agent: Mycobacterium leprae
■
Obligate intracellular, weakly acid-fast bacillus that
parasitizes macrophages and Schwann cells
■
Requires cool temperatures (30°C–35°C) for growth
n predilection for cooler areas of skin (nose, testes,
and ear lobes) and peripheral nerves that lie close to
skin surface
■
Transmitted primarily by nasal/oral droplets; also
nine-banded armadillos in SE United States
■
Cannot be cultured in vitro n must be cultivated in
mouse footpads or in armadillos
• Chronic, deforming disease characterized by skin and
nerve involvement
• Prolonged incubation period (avg. 4–10 years, but up to
30 years!); bimodal age range (10–15 years old and 30–60
years old); M . F
• Characterized by granulomas and neurotropism, both
within skin and peripheral nerves
• Primary skin lesion 5 erythematous, or hypopigmented,
annular anesthetic/hypoesthetic plaque w/ mild scaling
(Fig. 5.13)
• Peripheral nerves are enlarged in all forms (except
indeterminate)
■
Most commonly affects supercially located nerve trunks
(CN-5, CN-7, median, radial, ulnar, greater auricular,
posterior tibial, and common peroneal nerves)
■
Damage results in: “claw hand” and “papal hand”
exural deformities, stocking-glove anesthesia,
neuropathic ulcers of plantar surfaces, foot drop,
atrophy of interosseous muscles, and ocular damage
(because of CN-7 dysfunction)
• M. leprae–specic cell-mediated immunity (assessed
by lepromin skin test) plays a major role in the
Ridley-Jopling scale n divides leprosy into two polar
forms (Lepromatous/LL [Th2 response] and Tuberculoid/
TT [Th1 response]), and three borderline forms (BL, BB,
and BT) (Table 5.11)
■
Polar forms are stable! n patients in either polar form
(LL or TT) remain in this form throughout their disease
course
■
Borderline forms are unstable and have clinicopathologic
features somewhere in between the polar forms
• Indeterminate leprosy (earliest stage of leprosy): p/w
solitary, ill-dened hypopigmented macule, without
enlargement of peripheral nerves
■
Disease will either self-resolve, or evolve into one of
ve leprosy forms (LL, BL, BB, BT, or TT)
• Reactional states: abrupt-onset skin lesions that arise in
50% of patients during or after initiation of therapy
■
Type 1 (reversal reaction): result of change in cellmediated (Th1) immunity against M. leprae. May either
be downgrading (borderline leprosy patient who
“downgrades” toward lepromatous pole) or upgrading
(increase in cell-mediated immunity). Both may p/w
ulceration of existing lesions and preferential
targeting of nerves, resulting in dangerous neuritis
(5 emergency!); generally lacks systemic symptoms
(unlike type 2 reactions); highest risk with borderline
forms (BL . BB, BT); treatment 5 prednisone
■
Type 2 (erythema nodosum leprosum): Th2 (humoral)mediated formation of immune complexes, resulting in
multisystem vasculitis and EN-like lesions scattered at
previously unaffected skin sites (medial thighs and
extensor forearms are #1 sites); prominent systemic
symptoms; highest risk with LL and BL patients receiving
antimicrobial therapy; treatment 5 thalidomide
■
Lucio phenomenon: severe necrotizing vasculitis w/
thrombosis; occurs in patients from Mexico and
Central/South America with diffuse lepromatous
leprosy; p/w purpuric macules and ulcerative bullous
lesions below the knees n superinfection/sepsis;
treatment 5 prednisone
320
5.3 Bacterial Infections
Table 5.11 Polar and Borderline Leprosy
Clinical Findings Lepromatous (LL) Borderline (BB) Tuberculoid (TT)
Type of lesions Small hypopigmented macules,
Lesion number/size Innumerable, small Multiple (but countable); variable
Distribution Widespread and symmetric (face,
Circumscription Poorly defined lesions and difficult to
Sensation within lesions Normal
Site of nerve enlargement Symmetric and not a/w skin lesions Variable Asymmetric and localized around skin
Lepromin test Negative
Cell-mediated immunity None
Humoral immunity Strong Unstable None
Bacilli in skin lesions
AFB stain (Fite-Faraco
stain is best)
Histology Grenz zone, diffuse infiltrate of parasitized
Associated findings Acquired ichthyosis, saddle nose,
Other comments High risk for type 2 reaction
papulonodules, and diffuse infiltration (n
leonine facies, elongated earlobes, and
madarosis)
buttocks, legs)
discern edges
(Th2 .. Th1)
IL-4, -5, -10, -13
1111 (globi)
Multibacillary
1111 11
foamy histiocytes (Virchow cells),
plasma cells, free-floating clumps of
bacilli (globi) in dermis, and “onion-skin”
pattern around nerves; lacks well-formed
granulomas
lagophthalmos, corneal anesthesia,
blindness, and orchitis (n sterility and
gynecomastia)
Lesions do not have anhidrosis or alopecia
Histoid leprosy (subtype of LL)—dermato-
broma- and neurobroma-like lesions
Ziehl-Neelsen, Fite, Gram stains all (1)
for bacilli
False (1) VDRL, FTA-ABS
Plaques and dome-shaped lesions Dry, scaly, hypopigmented, and
sizes
Generalized but asymmetric Localized, asymmetric
Not as sharply defined as TT Well-defined; sharply demarcated
g
1 111
Unstable Strong
11
Multibacillary
Overlap of LL and TT findings,
organisms easily seen
Borderline categories (BL, BB, and
BT) are highest risk for type 1
reactions
BL is high risk for type 2 reaction
anesthetic plaques with raised
peripheral rim and central atrophy 1/–
alopecia and anhidrosis
One or few (,5); large
raised/indurated borders
Absent
lesions
(Th1 .. Th2)
IL-2, IFN-γ
None
Paucibacillary
Negative
Well-formed sarcoidal granulomas
w/ linear arrangement (East-West)
along nerves, numerous Langhans
giant cells, fragmented nerve fibers,
lacks organisms (no globi or Virchow
cells), and Grenz zone
One-sided neuropathic changes of
extremities (e.g., bone resorption n
short digits)
Skin lesions favor face, extremities, and
cool areas of trunk
TT often self resolves in 3 years
• Treatment (WHO recommendations):
■
Multibacillary (duration 5 12 months): rifampicin
600 mg Qmonth 1 dapsone 100 mg QD 1
clofazimine 300 mg once a month and 50 mg daily
■
Paucibacillary (duration 5 6 months): rifampicin:
600 mg Qmonth 1 dapsone 100 mg QD
■
Single skin lesion paucibacillary leprosy (duration 5
single dose): rifampicin 600 mg 1 ooxacin 400 mg 1
minocycline 100 mg
Atypical mycobacteria
• Mycobacterium avium complex: more commonly seen in AIDS
patients; found in environment (water, soil, and animals);
pulmonary infection is most common nding; skin ndings
w/ primary inoculation or via dissemination (pustules, ulcers
on legs, and nodules); h alkaline phosphatase; clarithromycin/
azithromycin 1 ethambutol 1/– rifampin
• Mycobacterium marinum: acquired via cutaneous contact
(usually hands w/ abrasions) with aquatic environments
(e.g., sh tanks and swimming pools) n erythematous/blue
ulcerating nodules in a sporotrichoid pattern; diagnosis is
conrmed with culture: M. marinum grows best at 31°C
(3 weeks required for growth), as opposed to the usual
37°C for most other mycobacteria; treatment: clarithromycin
1/– rifampin/ethambutol, minocycline, and TMP-SMX
• Mycobacterium ulcerans: aka Buruli ulcer; usually in Africa, in
areas close to water bodies; minor trauma n nodule n ulcer
on extremities; can become . 15 cm and extend to bones;
treatment: excision (treatment of choice), local heating,
rifampin 1 streptomycin 1 clarithromycin, and amputation
• Mycobacterium fortuitum, chelonae, and abscessus: rapid
growing mycobacteria (Table 5.12); saprophytic
organisms; can get infections post-trauma/surgery or
medical treatments (e.g., implant placement,
liposuction, and botulinum toxin)/tattoo/nail salon
footbaths; skin presentations vary, but most common is
inamed subcutaneous nodules in sporotrichoid
pattern; clarithromycin is treatment of choice, but
surgical treatment may be needed
321
CHAPTER 5 • Infectious Diseases
Table 5.12 Mycobacteria That Cause Cutaneous Disease
Group and Pigment Rate of Growth Pathogens
Slow growers
Photochromogens
Scotochromogens
Nonchromogens
Rapid growers 3–5 days M. fortuitum, M. chelonae,
Non-cultured
(to date)
a
Capable of yellow pigment formation upon exposure to light.
b
Capable of yellow pigment production without light exposure.
c
Incapable of pigment production.
d
Including bacillus Calmette-Guérin.
Modied classication of Runyon.
a
2–3 weeks
b
2–3 weeks
c
2–3 weeks M. tuberculosis, M. avium,
M. kansasii, M. marinum,
M. simiae
M. scrofulaceum, M. szulgai,
M. gordonae, M. xenop
M. intracellulare, M.
ulcerans, M. haemophilum,
M. malmoense, M. terrae,
M. genavense, M. bovis,
M. nonchromogenicum
M. smegmatis, M. abscessus,
M. immunogenum,
M. goodii, M. wolinskyi,
M. cosmeticum,
M. mucogenicum
M. leprae
d
5.4 FUNGAL DISEASES
I. Supercial mycoses
Dermatophytes
• Species—three genera: Microsporum, Epidermophyton, and
Trichophyton
■
Generally cause supercial skin infections and nail
infections
■
The most common organism(s) that cause(s) various
manifestations are as follows:
Tinea capitis—Trichophyton tonsurans (#1 cause in
United States), Microsporum canis (#1 cause
worldwide; more inammatory), and Tinea violaceum
(East Africa)
♦ Endothrix (black dot appearance from breakage
near scalp; arthroconidia within hair shaft): T.
rubrum, T. tonsurans, T. schoenleinii, T. yaounde, T.
violaceum, T. gourvilli, and T. soudanense (mnemonic:
“Ringo Gave Yoko Two Squeaky Violins”)
♦ Ectothrix (gray patch appearance 5 scaly patches
of alopecia; arthrospores around hair shaft)
Fluorescent (via Wood lamp—pteridine):
M. canis, M. audouinii (formerly #1 cause in
children), M. gypseum, M. ferrugineum,
M. distortum, and T. schoenleinii (mnemonic:
“Cats And Dogs Fight and Growl Sometimes”)
Nonuorescent: T. mentagrophytes, T. rubrum,
M. nanum, T. megninii, T. gypseum, and T.
verrucosum
♦ Favus—T. schoenleinii . M. gypseum, T. violaceum
♦ Kerion—M. canis, T. verrucosum, T. mentagrophytes,
and T. tonsurans
Majocchi granuloma—T. rubrum most common
Tinea corporis—T. rubrum most common
♦ Zoophilic species (i.e., in farmers and pets)—
T. verrucosum and M. canis
Tinea imbricata—T. concentricum
Tinea barbae—T. verrucosum, T. mentagrophytes,
T. tonsurans, and T. rubrum
Tinea faciei—usually zoophilic species (M. canis
and T. metagrophytes) . T. rubrum; most commonly
in kids after visiting rural areas
Tinea cruris—T. rubrum, E. occosum, and
T. interdigitale
Tinea pedis (Tinea manuum has same causative
organisms)
♦ Moccasin, interdigital, and ulcerative—T. rubrum
. E. occosum (mocassin), T. interdigitale
(interdigital)
♦ Vesicular/bullous—T. mentagrophytes
Onychomycosis
♦ Distal subungual: T. rubrum, T. interdigitale, and
E. occosum
♦ Proximal white subungual—T. rubrum
♦ h Risk in HIV
♦ White supercial—T. mentagrophytes (adults)
versus T. rubrum (children)
♦ Less common causes: Candida albicans (most
commonly in setting of mucocutaneous
candidiasis), Fusarium spp. (white supercial
onychomycosis), Scytalidium spp. (dark
onychomycosis with chronic paronychia), and
Scopulariopsis brevicaulis (white supercial
onychomycosis)
■
Geography—ubiquitous; fungi are classied according
to their normal habitat:
Anthropophilic: restricted to humans and cause a
chronic, mild inammatory response; includes
all Trichophyton spp. (except T. mentagrophytes and
T. verrucosum), E. occosum, M. audouinii, and
M. ferrugineum
Zoophilic: primarily affect animals; cause massive
inammatory response in humans; includes
M. canis (cats and dogs), M. nanum (pigs),
T. verrucosum (cattle), and T. mentagrophytes
(rodents)
Geophilic: found in soil; cause severe inammatory
response and scarring in humans; M. gypseum (soil)
is the only common species in this class
■
Histology—septate hyphae in stratum corneum or nail
plate, brisk dermal inammation (vs. minimal in
tinea versicolor) 1/– neutrophilic microabscesses in
epidermis or corneum/nail plate
PAS (red) and GMS (black)
■
Diagnosis—KOH (helps break down keratin making
fungi more visible) 1/– culture
Chlorazol black E—chitin stain—hyphae will be green
Calcouor white—chitin stain—blue or green with
uorescence microscopy
■
Pathogenesis: virulence factors (hydrolases and
keratinases) allow penetration into stratum corneum
322
5.4 Fungal Diseases
and the released enzymes induce inammation (Th1
response)
■
Clinical presentation:
Tinea corporis/cruris: annular/arcuate scaly patches/
plaques with inamed and possibly palpable
borders 1/– pustules; tinea cruris spares scrotum
(unlike candidiasis)
Tinea pedis: erythema with scale, especially between
toes (maceration) and sides of feet
■
Tinea manuum: non-erythematous scaling (1/–
collarettes of scale) of palm of one hand 1 moccasintype tinea pedis; treat with systemic antifungals
Tinea capitis: circular scaling patches 1/– pustules
1/– LAD; may have black dots from broken hairs in
endothrix infections; treat with systemic antifungals
♦ Usually school age children; h in blacks/males
♦ Kerion: boggy inamed nodule/abscess with
pustules and possible LAD which may n scarring
♦ Favus: yellow cup-shaped crusts (scutula) that
cluster together, resulting in a honeycomb
appearance and can n scarring
♦ Green uorescence of infected hairs with Wood
lamp may be seen with Microsporum infection
♦ Dermatoscopy: comma and corkscrew hairs
Tinea imbricata: concentric and polycyclic rings of
scale
Majocchi’s granuloma: erythematous papules/nodules
around hair follicles, particularly lower legs (may arise
from tinea pedis); treat with systemic antifungals
Tinea faciei: erythematous follicular-based papules,
often in an annular distribution most common in
kids; treat with systemic antifungals
■
Treatment: topical or systemic terbinane or azole
antifungals, topical naftine
Terbinane and griseofulvin have equivalent safety/
efcacy in children in the treatment of tinea capitis;
terbinane more effective for T. tonsurans and
griseofulvin more effective for Microsporum
Onychomycosis: systemic terbinane is most
effective but itraconazole/uconazole can be used
particularly in non-dermatophyte onychomycosis;
tavaborole, ciclopirox, and enaconazole solutions
are not as effective but safer
Tinea versicolor (pityriasis versicolor)
• Species: Malassezia globosa and M. furfur; yeast form is
normal skin ora; transforms to lamentous/hyphal form
in disease states; culture requires olive oil for growth
• More common in darker skin/adolescents/summer
• Histology: hyphae and spores (“spaghetti and
meatballs”) seen in stratum corneum (also on KOH)
• Pathogenesis: overgrowth of normal ora, which is
ubiquitous (esp. with warmth and humidity in the right
host); hypopigmentation due to melanocyte inhibition
by azelaic acid (dicarboxylic acid byproduct of Malassezia)
• Clinical presentation: hyper- or hypopigmented nely scaling
circular/oval macules/patches in sebaceous distribution
(scalp, face, neck, upper chest, and upper back)
• Treatment: topical or systemic azole-antifungals,
selenium sulde shampoo, or topical ciclopirox
Piedra
• Species:
■
Black—Piedra hortae
■
White—Trichosporon asahii (most strongly linked to
white piedra; may cause disseminated disease in
immunocompromised patients), T. ovoides, T. inkin,
and T. cutaneum
• Geography: tropical
• Pathogenesis: found in water and soil in tropics
• Microscopy: black or white concretions along hair
(encircle hairs, unlike the sac-like appearance of lice)
■
White piedra with soft mobile nodules; black piedra
with hard nonmobile nodules
• Clinical presentation: asymptomatic hair breakage on
scalp, axillary, and pubic region
• Treatment: hair shaving/cutting and antifungal
shampoos; systemic antifungals if recalcitrant
Tinea nigra
• Species: Hortaea werneckii
• Geography: tropical and subtropical, especially
coastal
• Microscopy: dark brown septate hyphae with budding
yeast in thickened stratum corneum
• Pathogenesis: overgrowth of fungus
• Clinical presentation: dark-brown/black macule or small
patch on palms/soles, limited to stratum corneum
• Treatment: azole creams, Whiteld’s ointment; oral
terbinane if recalcitrant
II. Subcutaneous mycoses
Sporotrichosis
• Species: Sporothrix schenckii
• Geography: ubiquitous saprophyte; endemic to Central/
South America and Africa
• Microscopy: usually not well-visualized with stains;
granulomatous inammation with plasma cells and
asteroid corpuscles (Splendore-Hoeppli phenomenon);
organisms are cigar-shaped budding yeast
• Pathogenesis: traumatic inoculation from soil via plant
thorns, wood splinters, and sphagnum moss .. cats/
rodents/armadillo bites; inhalation of spores
• Clinical presentation: multiple ascending ulcerated
nodules or subcutaneous abscesses, most frequently in
gardeners, agriculture/farm workers, and veterinarians
■
May n erythema nodosum
• Treatment: obtain fungal culture (difcult to nd in
tissue samples), itraconazole (treatment of choice),
SSKI, and amphotericin B in disseminated disease
(Box 5.3)
Box 5.3 “No SALT” Mnemonic
Sporotrichoid spread: Nocardia, Sporotrichosis, Atypical mycobacteria,
Leishmaniasis, Tularemia (No SALT)
323
CHAPTER 5 • Infectious Diseases
Lobomycosis
• Species: Lacazia (Loboa loboi)
• Geography: infects freshwater dolphins in South
American rivers
• Microscopy: thick-walled yeast with tubular connections
between cells—“pop bead” or “chain of coins” appearance
• Pathogenesis: unable to be cultured in vitro
• Clinical presentation: keloid-like verrucous brotic
nodules that can ulcerate; ear helix #1 site; men ..
women; rural areas
• Treatment: surgical excision
Mycetoma (madura foot)
• Species:
■
Eumycetoma (fungus)—Madurella spp. Pseudallescheria
boydii (most common), Exophiala jeanselmei, and
Acremonium spp.
■
Actinomycetoma (bacteria)—Nocardia (N. brasiliensis
[#1 bacterial cause] and N. asteroides both have white
grains), Actinomadura spp. (A. pelletieri 5 red grains;
A. madurae 5 cream or pink grains), and Streptomyces
somaliensis (yellow grains)
• Geography: southern tropics (Latin America, India, and
Africa), a/w poverty and bare feet; young men
• Microscopy: granulomatous reaction with grains; serologic
testing used because of culture difculty
• Pathogenesis: traumatic inoculation
• Clinical presentation (Fig. 5.14): slow progression of
tumors (tumefaction) with sinus tracts draining grains,
which are fungal or bacterial aggregates; most common
on feet/lower legs; long-standing lesions n bone and
visceral involvement
■
Black grains only seen in eumycetoma and red
grains only seen in actinomycetoma (specically
A. pelletieri)
• Treatment:
■
Actinomycetoma: streptomycin/amikacin 1 TMP-SMX
■
Eumycetoma: surgical debridement and several month
courses of azole antifungals
A
B
Fig. 5.14 Mycetoma cases produced by Nocardia brasiliensis (A) Inammation
of the dorsum of the foot and ankle showing abscesses and sinuses. (B) Mycetoma of the back of the neck. (From Welsh O, Vera-Cabrera L, Salinas-Carmona
MC. Mycetoma. Clin Dermatol. 2007;25[2]:195–202.)
Chromoblastomycosis
• Species: Fonsecaea pedrosoi (most common), Fonsecaea
compacta and Fonsecaea monophora, Rhinocladiella aquaspersa,
Phialophora verrucosa, and Cladophialophora carrionii
• Geography: tropical and subtropical climates; found in
decaying vegetation and soil
• Microscopy (Fig. 5.15): pseudoepitheliomatous
hyperplasia (PEH), granulomatous dermal inammation
with medlar bodies (pigmented muriform cells, “copper
pennies”)
• Pathogenesis: traumatic inoculation by thorns or splinters
• Clinical presentation (Fig. 5.16): weeks to months after
inoculation of lower extremity, pruritic papules/nodules
expand n verrucous plaque with black dots; does not
invade muscle or bone; chronic lesions can n SCC
• Treatment: itraconazole, 5-ucytosine 1 amphotericin B,
voriconazole; surgical excision for small lesions
324
Fig. 5.15 Fumagoid cells, or sclerotic or Medlar bodies. (H&E, original magnication 40×) (Courtesy of Dr. Derek Marsee, Diagnostic Pathology Medical Group.)