Granulomatous Infection

By admin On Oct 9, 2024

Ovid: Oncology and Basic Science

Editors: Tornetta, Paul; Einhorn, Thomas A.; Damron, Timothy A.

Title: Oncology and Basic Science, 7th Edition

> Table of Contents > Section
IV – Basic Science > 27 – Infectious Disorders of Bone and Joint
> 27.2 – Granulomatous Infection

27.2

Granulomatous Infection

Granuloma is defined as a microscopic-sized aggregation
of histiocytes and hypertrophied fibroblasts termed epithelioid cells,
centrally located and rimmed by a chronic inflammatory infiltrate of
lymphocytes and plasma cells (Fig. 27.2-1). The
entire focus can be surrounded by a ring of fibrosis. Multinucleated
giant cells, with a characteristic positioning of the nuclei at the
periphery of the cell (foreign body or Langhans giant cells), are
frequently present (Table 27.2-1). Over time
the granuloma may be replaced by scarring and even calcification. In
tuberculosis, the central area may undergo caseous (cheese-like)
necrosis.

Conditions associated with granulomatous histology (see Fig. 27.2-1) include:
- Infection by mycobacteria, fungi, or parasites
- Foreign materials
- Eosinophilic granuloma
- Sarcoidosis
  
  The response in bone is indolent, with slowly enlarging
  lytic defects in bone with smooth walls accommodating confluent,
  usually caseating granulomas.
Eosinophilic granuloma (Langerhans cell
histiocytosis or Langerhans cell granulomatosis) only infrequently has
clear-cut granulomatous histology (see Table 27.2-1).
This disorder can progress with rapid local osteolysis (unique among
granulomatous bone processes, which are usually indolent).

Mycobacterial Osteomyelitis

Tuberculosis (TB) will be discussed in detail as the prototype disorder in this section.

Pathophysiology

General

Tubercle bacillus induces an acute
inflammatory response on entry into host tissue that usually controls
the infection, walling it off to form a primary complex; if infecting
dose overwhelms the response, the infection persists and spreads;
during the early stages, bacilli may move into the circulation and
metastasize to central nervous system, bones, or liver.
PMNs, on ingesting the bacilli, may necrose and become engulfed by macrophages and mononuclear cells.
Macrophages adopt epithelioid morphology
on accepting the lipids of the bacilli, or may aggregate to form
Langhans giant cells, whose task is to digest and remove the bacilli;
these cells may also be overcome by the bacillus, also necrosing and
inducing further phagocytic activity. Necrosis of epithelioid and
Langhans cells becomes confluent (caseating).
After 1 week, lymphocytes form a ring around the periphery of the lesion, forming a 1- to 2-mm nodule known as the tubercle.
During the second week caseation starts to occur, induced by the protein fraction of the tubercle bacilli.
Over time, the PMN response is replaced
by chronic inflammatory round cell infiltration accompanied by a
fibroblastic proliferation that is variable in degree around the
tubercle (chronic inflammatory focus).

This immune response usually will control
the infection, in essence walling it off, where it can lie dormant for
a lifetime, potentially becoming active as old age and impaired immune
response occur.

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Figure 27.2-1 Granuloma (TB).
(A) Granuloma formation is present. At this power, cellular detail is
not visible, but there are four granulomas present, each within a ring
of fibrosis. The center of the granuloma may manifest caseous necrosis;
these granulomas are in the earliest stages of central necrosis. There
are multinucleated giant cells of the Langhans or foreign body type
frequently found in the granuloma. (B,C) Caseating granuloma (TB). (B) Here, granulomas are seen replacing normal marrow elements within bone. (C)
Necrotic material is seen on the left, and the intermediate margin
shows epithelioid cells centrally, with inflammatory cells
(lymphocytes, plasma cells on the right, and a Langhans giant cell).
Langhans cells have peripherally placed nuclei and are the cells to
study carefully for the presence of acid-fast bacilli or fungi. (D,E) Granulomatous osteomyelitis (foreign body).
Strictly speaking, a granuloma is a microscopic structure formed by two
or more histiocytes or macrophages. They tend to have a nodular or
circumscribed appearance and can be non-necrotizing or necrotizing. (D)
In this photomicrograph, well-formed non-necrotizing (noncaseating)
granulomas of histiocytes and multinucleated giant cells are evident,
surrounded by fibrous connective tissue. Granulomas on hematoxylin and
eosin stain are not specific, and their evaluation requires an
evaluation of special stains and examination under polarized light
(birefringent foreign particles are highlighted in this manner). (E) Higher-power view of D
brings out the details of a single foreign body granuloma. Note the
multinucleated giant cell and the surrounding plump mononuclear cells
(histiocytes/macrophages). The vacuolated cytoplasm of the
multinucleated giant cells underscores the brisk metabolic activity of
these phagocytic cells. (F–H) Granulomatous (fungal, mycotic) osteomyelitis secondary to Cryptococcus infection. (F)
This field shows a mixed inflammatory infiltrate with a few small
discrete noncaseating granulomas composed of histiocytes and a few
giant cells. Note the pale blue spherical structures within the
cytoplasm of some of the histiocytes. Special stains (e.g., GMS and PAS
stains) are useful for identification of the organism. (G) Higher-power view of F
brings out the details of the histiocytes and multinucleated giant
cells. A few gray-blue intracellular spherical bodies suspicious for
fungi are noted. (H) Same view as in G
with PAS stain (one fungal organism positive), which brings out a
dark-pink spherical structure that is morphologically consistent with
the yeast form of Cryptococcus species (this species has a capsule rich in mucin, which is readily stained by PAS).

Musculoskeletal lesions form by metastasis from 3 months to 3 years after the primary infection.

Spine

Children: Spine involvement begins in the vertebral body, usually anteriorly, then extends to adjacent disc and vertebral body.
Adults: Onset is beneath the periosteum
under the anterior longitudinal ligament and may spread up and down the
spine, bypassing some vertebrae to lodge at more than one level; disc
space narrowing, vertebral body destruction, collapse with kyphosis,
and eventual fusion may occur after 1 to 2 years.

Extraspinal

Unlike bacteria, TB does not produce
proteolytic enzymes that aggressively destroy cartilage, affording more
time to make the diagnosis before the joint is destroyed in tuberculous
arthritis.

Bacillus lodges in synovium and proliferates, opposed by the immune process in sequence as outlined above.

The inflamed synovium enlarges to fill all recesses

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of the joint, spreading over the cartilage from the periphery as a
pannus, mechanically eliminating nutrition of the cartilage from the
surface.

Table 27.2-1 Langhans Versus Langerhans Cells

	Langhans Cells	Langerhans Cells
Appearance	Giant cells with nuclei distributed around the periphery	Histiocytes with typical coffee-bean cleaved nuclei (NOT giant cells)
Associated conditions	Tuberculosis, foreign body granulomas	Langerhans cell histiocytosis or Langerhans cell granulomatosis or eosinophilic granuloma (older terminology)

Central joint space is preserved for months.

Cold abscess
- A marked exudative reaction consists of serum, PMNs, caseous material, bone debris, and tubercle bacilli.
- This collection migrates under the
  influence of gravity and may present along the spine and pelvis, in the
  groins, or about involved joints.
- It may present through the skin as a
  sinus or ulcer, which may then become secondarily infected, obscuring
  the diagnostic picture.
Regional osteopenia
- The inflammatory process induces an
  active hyperemia with osteoclastic deletion of bone, resulting in
  marked regional osteopenia.
Kissing sequestrate
- The inflammatory synovial mass invades weakened subchondral bone from the periphery.
- Rarely, sequestration of the opposing
  joint surfaces can occur as a result of this bone destruction, leading
  to the radiographic picture of “kissing sequestrate.”

Etiology

Causative organisms include Mycobacterium tuberculosis (TB), Mycobacterium leprae, and environmental mycobacteria.
Organisms grow on enriched medium slowly so that colonies appear at 2 to 4 weeks.
- Acid-fast stain may reveal classic “red snappers.”

Epidemiology

One third of global population is infected with TB; most frequent cause of death and disability worldwide.
U.S. statistics
- 10 million are infected; 90% of new activated cases come from this pool.
- In non-Hispanic whites, median age at diagnosis is 61; among minority groups it is 39.
- Americans >65 represent 6.5% of population but account for 26% of reported cases.
- 20% of new cases of TB have extrapulmonary disease.
- 33% of patients with TB and HIV have extrapulmonary disease.
- 1% to 3% of patients with TB develop musculoskeletal manifestations.

Diagnosis

Clinical Presentation

Classic: Patient becomes insidiously ill and develops chronic local musculoskeletal pain, fever, and weight loss.
Initial presentation may include:
- Cold abscess: juxta-articular or paraspinal soft tissue mass without inflammation
- Spinal involvement: may be truncal
  rigidity, muscle spasm, and neurological signs and deficit; spinal
  deformity (gibbus) is a late finding
- TB arthritis: more common than TB osteomyelitis
- Dactylitis: Small joints of the hands and
  feet are infrequently involved except in infancy, when digits may be
  involved with swelling.
- Osseous disease: occurs by metastatic
  spread from an initial focus, usually the lungs, with involvement most
  often of spine (lower thoracic most frequent, with multiple vertebral
  bodies in 50% of cases), followed by pelvis in 12%, hip and femur 10%,
  knee and tibia 10%, hand, and any other joint
Important clinical points
- Diagnosis can be difficult in the elderly, whose presentation may initially be only nonspecific constitutional symptoms.
- If you suspect musculoskeletal TB, check the lungs, kidneys, and gastrointestinal tract.

Radiologic Features

No pathognomonic features

Joints

Osteopenia and soft tissue swelling with
minimal periosteal reaction early, then marginal deletion of
subchondral bone on both sides of the joint with late loss of central
joint space (Fig. 27.2-2)

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Figure 27.2-2 (A)
TB of the knee. When TB first lodges in the synovium of a joint, it
creates many tubercles (usually small, without caseation) and induces
marked synovial proliferation. The suprapatellar pouch in this knee is
filled with inflamed synovium with histology as in Figure 27.2-1. There is significant osteopenia. (B–D) TB of the hip. (B)
Once the infection is established, the inflamed synovium invades the
joint space from the margins, growing as a pannus as in rheumatoid
arthritis, destroying the underlying cartilage by interfering with the
diffusion of nutrients to the cartilage. The joint surface is usually
preserved centrally until the process becomes much more advanced.
Synovial pathology involves both sides of the joint. TB must be in the
differential diagnosis for any periarticular disorder involving more
than one bone around a joint area or marginal erosions. (C) Photomicrograph of the edge of a joint showing the pannus growing from the right onto the underlying articular cartilage. (D) This higher-power view shows complete destruction of the cartilage by the pannus.

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Subchondral cysts
Enlargement of epiphysis
Subchondral erosions may cross epiphysis in one third of children affected.

Spine
- Rarefaction of vertebral endplates
- Increasing loss of disc height
- Focal bony destruction with disc involved and late vertebral body collapse (Fig. 27.2-3)
- Paravertebral soft tissue mass often present
- Needle biopsy in HIV/TB patients must rule out other diseases such as Kaposi sarcoma.

Mycotic Osteomyelitis

Occurs mostly in immunocompromised
patients or as opportunistic infections in individuals exposed to the
specific contaminated environment (workers)
Fungal infection mimics TB, so always culture for fungi if granulomatous pathology is found (see Fig. 27.2-1).
Radiographic differential includes myeloma and metastasis (due to frequent multifocality).
Relevant features of the fungal infections of the musculoskeletal system are outlined in Table 27.2-2.

Sarcoidosis

A systemic granulomatous disorder of unknown cause; no known organism

Figure 27.2-3
Gross specimen of TB of the spine. There is marked destruction of the
bony architecture, with extension of the granulomatous process
extending posterior to compress the cord. This degree of destruction
can produce spinal deformity and paraplegia.

Differential diagnosis in any clinical situation manifesting granulomatous histology

Diagnosis

Clinical Presentation

Typical patient is an adult, more commonly African-American, age 20 to 40 years, with fever, fatigue, malaise, and weight loss.
Affects lungs (90%), lymph nodes, skin, skeleton
- Skeletal distribution: hand (“sausage fingers”), wrist, foot, skull, vertebral bodies, long bones, synovium
- Typical musculoskeletal presentation: swollen, mildly painful fingers

Radiologic Features

No large destructive lesions as seen more commonly with TB
Mixed lysis and sclerosis is typical.
Hands/feet: punched-out cortical lesions,
with trabecular resorption (honeycomb lytic pattern) and linear
end-osteal sclerosis (acro-osteolysis; Fig. 27.2-4)

Laboratory Findings

Elevated angiotensin-converting enzyme (ACE) derived from epithelioid cells
Hypercalcemia arising from overproduction of 1-25-(OH)-D3, driven by activated pulmonary macrophages
Cultures negative

Pathologic Findings

Mimics TB but without caseation (see Fig. 27.2-4)
Giant cells show nonspecific cytoplasmic inclusions.
- Asteroid body: a central core of degenerating organelles encompassed by rays of collagen
- Schaumann bodies: large, concentrically laminated concretions of a protein matrix impregnated with calcium and iron salts

Treatment

Symptoms are usually self-limited. If severe, prolonged treatment with corticosteroids may be attempted.
Immunosuppressive agents, such as methotrexate, azathioprine, and cyclophosphamide can be used.
Rarely, some individuals with irreversible organ failure require organ transplantation.

Rare Forms of Osteomyelitis

These conditions, whose relevant information is outlined in Table 27.2-3, include:

Brucellosis
Cat-scratch disease
Microangiopathic osteomyelitis
- Syphilis
- Lyme disease
Fibrosing osteomyelitis (fibrocystic)
- Ecchinococcosis

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Table 27.2-2 Fungal Forms of Osteomyelitis

Organism	Entry	Skeletal Manifestations	Pathology	Diagnosis	Treatment
Blastomycoses dermatidis	Inhalation of conidia; they convert to yeast form in lungs and then disseminate systemically	Primary presentation in 10% with septic arthritis or osteomyelitis	Neutrophils ingest but cannot destroy organism; pus plus noncaseating granulomas termed pyogranulomas	Yeast forms: 8 to 15 mm, multinucleated (8 to 12), thick double-contoured cell walls; single broad-based budding	Amphotericin B; ketoconazole; surgery according to stage of disease
Histoplasmosis capsulatum; Midwestern and south-central U.S.	Inhalation of conidia from infected soil and bird droppings, same sequence as for B. dermatidis	African variant with skeletal infection 50% (H. capsulatum diboisii, large yeast, 10 to 15 mm); 50% incidence of skeletal lesion (skull, ribs, long bones, spine); eccentric, punched-out area of lysis	Suppurative areas mixed with epithelioid giant cell pyogranulomas; African histology contains large giant cells containing many yeast forms	Yeast forms 3- to 4-mm, spherical to oval, uninucleate, thin-walled, narrow-based budding	Primary: ketoconazole or itraconazole Secondary: amphotericin B for systemic, severe infection
Coccidioides immitis; arid regions of southwest U.S., Mexico, and Argentina	Same sequence as for B. dermatidis Infection—direct link to exposure 40%: symptomatic disease, usually lung 90% resolve 10% lung sequelae 1% have dissemination; of these one third have multisystem disease	Arthritis, tenosynovitis, osteomyelitis Lytic, unifocal in 60%, wide distribution; vertebral lesions often multiple, may spare the disc and extend to posterior elements and ribs. Joint lesions are unifocal in >90%; knee and ankle predominate.	In joints, primary response is neutrophils and macrophages, changing at 1 week to granulomatous inflammation to developing spherules; new endospores elicit a neutrophil response, initiating a new cycle.	In lungs conidia enlarge, become spherules 10 to 15 mm with thick double-contoured walls and many endospores, which then rupture.	Immobilization Synovectomy Oral ketoconazole, itraconazole, or amphotericin B systemic with or without intra-articular
Cryptococcus neoformans; world-wide distribution	Soil fungus disseminated by excreta of pigeons produces asymptomatic lung infection in the immunocompetent host.	In immunodeficient may disseminate to central nervous system, skin, and bone. Bone lesions 5% to 10%: distribution—pelvis, femur, spine, tibia, and scapula, causing chronic pain and swelling in some; some are asymptomatic	Inflammatory response varies with usual lymphocytes and plasma cells, with or without large neutrophils and giant cells; granulomas absent usually.	Pleomorphic encapsulated yeast form, 2 to 20 mm, reproduces by budding.	In the absence of AIDS for disseminated disease, amphotericin B and flucytosine; surgery rarely used
Sporothrix schenckii; tropical America	Direct inoculation into the skin of hands or feet; rare inhalation	Typical in gardeners handling roses and sphagnum moss; local painless mobile nodule becomes red and soft and ulcerates; secondary lesions follow lymphatics; ulcers present for years; regional lymph nodes enlarge; local spread to bone/joint mimicking TB	Pyogranulomas	Dimorphic fungus: hyphal form in vitro at <37 degrees; in vivo, 2- to 6-mm oval to cigar-shaped yeast forms with unequal budding	Cutaneous treatment: saturated potassium iodide, 50 mg/day for 6 weeks Surgery plus amphotericin B for bone and joint manifestations
Candidiasis	Systemic dissemination: neonates/immunocompromised patients Cutaneous and mucous membrane portals	Hematogenous spread to bone and joint with a radiologic picture mimicking TB; clinical setting immunocompromised patients, neonates, rare case reports of candidal total joint infection	Mimics TB; combination of immune impairment and broad-spectrum antibiotics creates opportunity for pathogenicity.	>150 candida species exist, normally inhabit mucous membranes or damaged skin	Amphotericin B Rarely surgery

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Figure 27.2-4 Boeck’s sarcoid. (A) Radiograph shows a small lytic lesion with sclerotic borders in the proximal phalanx of the great toe. (B) A small tubercle in sarcoid, with each of the cellular elements of a granuloma demonstrated.

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Table 27.2-3 Rare Forms of Osteomyelitis

Organism	Entry	Clinical Manifestations	Pathology/Skeletal Involvement	Diagnosis	Treatment
Brucella (gram-negative coccobacilli)	Gastrointestinal: Goat’s milk, B. melitensis Cow’s milk, B. abortus Exposure to infected cattle, B. abortus Swine, B. suis Dogs, B. canis	Acute (malignant) form: overwhelming infection with fever, chills, collapse, reticuloendothelial system [RES] activation (lymphadenopathy, hepatosplenomegaly), delirium, coma, early death Recurrent (undulant fever): B. melitensis presents with flu-like symptoms with relapses. Chronic (intermittent): B. abortus (rare) presents with malaise, mild fever, weakness.	20% to 60% with septic arthritis, osteomyelitis, tenosynovitis, bursitis Sacroiliitis is most common location; TB-like spinal presentation in elderly. Radiographs mimic TB spinal and peripheral. Microscopy: B. melitensis and suis—necrotizing granulomas mimic TB. B. abortus—non-necrotizing granulomas mimic sarcoid.	Culture of blood, marrow, and infected tissue Serologic testing: serum agglutination or ELISA Difficult to stain and identify in infected tissue	Tetracycline with rifampin; or tetracycline with minocycline; or ciprofloxacin Surgery as indicated clinically
Cat-scratch disease (Bartonella henselae)	Skin puncture	Initial papule at inoculation site in 3 to 10 days, then regional lymphadenopathy (months to years), then systemic spread to RES and bone. Initial mild flu-like symptoms. Nodes may suppurate and drain through skin. Rare rash, conjunctivitis.	Bone involvement near skin lesions, mixed lysis/sclerosis. Microscopy: granulomas with rare giant cells, undergo necrosis with coalescence to form confluent microabscesses. Neutrophils common in early lesions.	Raised white blood cell count, erythrocyte sedimentation rate, eosinophilia (10% to 20%), positive skin test (90%), IFA Ab titer >1:64; positive culture; polymerase chain reaction (PCR) of DNA	No specific antibiotic therapy has proven useful. No treatment is indicated in normal host; self-limited condition. Symptomatic relief (no effect on duration of symptoms) with 5-day course of azithromycin. In immunocompromised host choices include trimethoprim– sulfamethoxazole; gentamicin; ciprofloxacin; rifampin.
Syphilis (Treponoma pallidum, a spirochete)	1. Direct: Mucosal surface entry is followed by 3 stages: a. Primary: incubation 10 to 90 days, then chancre + regional lymph node enlargement (50%) b. Secondary: 6 to 24 weeks, systemic infection to every system (“the great imitator”), followed by latency, early phase (4 years) retaining infectiousness (25%) followed by late noninfectious latent syphilis c. Tertiary: years to decades, presents with gummas in any system 2. Indirect: Congenital: intrauterine transmission from mother to child	Direct syphilis presents in the benign tertiary (gummatous) stage in the skeleton (50%) with bone pain (+/-) and local swelling without local signs of inflammation. Indirect syphilis may be: Early in first 2 years; infectious, resembles severe secondary syphilis in adult; Late, after 2 years; noninfectious; Residual stigmata: Hutchinson’s teeth (centrally notched, widely spaced upper central incisors); “mulberry molars” (6-year molars with multiple cusps); abnormal facies (frontal bossing, saddle nose, poorly developed maxilla); saber shins (anterior tibial bowing). There are numerous other rare manifestations.	Skull, tibia (anterior aspect), clavicle are preferred sites of osteomyelitis. Inflammation is a periostitis with microangiitis, gummatous change, and granulomas, with possible spread to overlying skin and medullary space. Moth-eaten changes + sclerosis represent destruction induced by gummas (mimics chronic suppurative osteomyelitis). Septic arthritis of syphilis: painful, symmetric swelling of knee, elbow, ankle, shoulder, and wrist, with normal range of motion; spread is contiguous from osteomyelitis. Early congenital syphilis: symmetrical widespread osteochondritis and perichondritis affecting the most rapidly growing area (ends of cartilage model bones) progressing during first 6 months, then subsiding. Periostitis continues and becomes apparent between the ages of 5 and 20.	Serologic tests: rapid plasm reagin (RPR) test: reflects disease activity VDRL slide flocculation test: reflects the exact titer of serum regain antibody. Specific anti-treponemal antibody.: FTA-ABS is the standard test; T. pallidum hemagglutination tests (MHA-TP and TPHA) are convenient but less sensitive than the FTA-ABS test for detection of primary syphilis. Both the MHA-TP and FTA-ABS tests are very specific and have high positive predictive value when used for confirmation of positive reaginic tests.	Penicillin
Lyme borreliosis; zoonosis transmitted by ticks, disease affecting skin, central nervous system, the heart, and joints	Causative organism: spirochete Borrelia burgdorferi – Northern hemisphere distribution – Reservoirs of spirochete are intermediate and small mammals, and birds. – Ticks transmit the organism to man; species is Ixodes, and geni include dammini, pacificus, and scapularis in North America	3 clinical stages: – Not all stages need appear, and they may overlap. Stage I: erythema migrans with centrifugal spread, 3 days to 16 weeks after tick bite, flu-like symptoms Stage II: weeks to months later, central nervous system, cardiac, skin, and joint symptoms appear. Other manifestations include lymphadenopathy, inflammatory eye disorders, hepatomegaly, testicular swelling, and hepatitis. Stage III: Chronic organ involvement affects joints (arthritis), skin, central nervous system, heart, muscles, and bone marrow.	In various organ systems the lesions are a chronic inflammatory infiltrate consisting of lymphocytes, plasma cells, and histiocytes. There is a microangiitis with perivascular cuffing by mononuclear cells resulting in an endarteritis obliterans, similar to syphilis. In joints the response is similar to rheumatoid arthritis histologically with a pannus invading the joint. The organism resides extracellularly but may attach to and invade some cells (fibroblasts and endothelial cells). B. burgdorferi activates inflammatory cytokines affecting joints (interleukin-1 and tumor necrosis factor alpha [TNF-α]). Possible immunogenetic predilection for Lyme disease in those with HLA-DR4 genotype.	Organism is difficult to culture. Identification is by silver stains and immunohistological techniques. Polymerase chain reaction testing is not yet validated. Culture and biopsy identification is thus difficult. Serologic testing: enzyme-linked immunosorbent assay (ELISA), indirect immunofluorescence assay (IFA), and Western blot. Stage I: less than half have detectable antibodies, mostly IgM. Stage II: 70% to 90% have antibodies, mostly IgG. Confirm with Western blot, and repeat if negative.	For systemic disease: doxycycline, cefuroxime axetil, or erythromycin. For arthritis, repeat 30-day courses of doxycycline, amoxicillin, plus probenecid.
Ecchinococcosis (hydatid cyst); parasitic infestation by a tapeworm	Ecchinococcosis species include granulosis (most common cause of unilocular hydatid cyst); vogeli (canine tapeworms); multilocularis (causes multilocular cysts) Disease of canines in which herbivores (sheep, deer, cattle) serve as intermediate host. Man inadvertently ingests tapeworm eggs from contaminated food or water.	Asymptomatic until cyst enlargement affects organ of involvement: liver, lungs, muscles, bones, kidneys, central nervous system, and spleen. There is a slow enlargement of the cyst with possible vague pressure effects; mass then can impinge, obstruct, or rupture. In bone: The cysts can be an incidental finding; mass effect: vague pain; pathologic fracture; vertebral body: nerve or cord compression.	Intraosseous lesion: large, multiloculated, distorted fluid-filled cyst, lined by gelatinous tissue, usually sterile. Early marrow response: Local marrow necrosis Mixed inflammatory infiltrate with eosinophils, and giant cells, hemosiderin deposits, and cholesterol crystals	ELISA or Western blot serology (>80% sensitive and specific for liver infection); radiology, ultrasound, computed tomography, and magnetic resonance imaging allow imaging of the cysts.	Surgical resection is the primary treatment. Medical management is indicated in patients with primary liver and lung cysts that are inoperable, or those who have multiple cysts. Benzimidazoles are used and the response rates are not encouraging (30% cure, 30% to 50% improvement with reduction in cyst size, and 20% to 40% no change).

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