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SKELETAL MANIFESTATIONS IN
HIV
Presentor:
Dr.Pavan kumar
Moderator:
Dr. Prashant Sir
Head of orthopaedics
department:
Dr. Nagendra babu sir
TOPICS
• INTRODUCTION
–HISTORY
–PROBLEM STATEMENT
–MORPHOLOGY OF HIV
–IMMUNOPATHOGENESIS
–VIRAL LIFECYCLE
• EPIDEMIOLOGICAL FEATURES
• CLASSIFICATION and DEFINITION
–CDC CLASSIFICATION AND DEFINITION
–STAGING BY CD4 CELL COUNT CLINICAL
MARKERS OF HIV DISEASE PROGRESSION
–WHO DEFINITION OF AIDS
–EXPANDED WHO CASE DEFINITION FOR AIDS
SURVEILLANCE
–WORLD HEALTH ORGANIZATION STAGING OF
HIV/AIDS
• CLINICAL MANIFESTATIONS
• MUSCULOSKELETAL MANIFESTATIONS IN HIV
INFECTED PATIENTS
–REACTIVE ARTHRITIS
–REITER'S SYNDROME
–PSORIASIS AND PSORIATIC LIKE ARTHRITIS
–SEPTIC ARTHRITIS
–HIV ASSOCIATED ARTHROPATHY
–PAINFUL ARTICULAR SYNDROME
–OSTEOMYELITIS
–MYOSITIS
–IDIOPATHIC POLYMYOSITIS
–OTHER MUSCULOSKELETAL MANIFESTATIONS
OF HIV
–MANIFESTATIONS OF DRUG TOXICITY
• RISKS AND PREVENTION
–AAOS RECOMMENDATIONS FOR OPERATING
ROOM PROCEDURES
–UNIVERSAL PRECAUTIONS
–LABORATORY DIAGNOSIS OF HIV
–CAUSES OF FALSE-POSITIVE AND FALSE-
NEGATIVE REACTIONS IN ENZYME
IMMUNOSAYS FOR ANTIBODY TO HIV
–CONTROL OF AIDS
–POST-EXPOSURE PROPHYLACTIC TREATMENT
• CONCLUSION
• REFERENCES
HISTORY
• AIDS was first recognized in USA in the summer of 1981 by CDC which reported
unexplained occurrence of pneumocystitis pneumonia in a cohort of homosexual
men. Within months disease became recognized among male and female IV drug
users and soon thereafter in recipients of blood transfusion and in haemophiliacs.
After the diagnosis of AIDS, the human immunodeficiency Virus was identified and
was found to cause this disease.
• I983 - Pastuer institute in Paris isolated a retrovirus from a patient with persistent
lymphadenopathy and was called lymphadenopathy associated virus (LAV).
• 1984 - It was named HTLV—III by Gallo and it was proved to be the causative
agent.
• 1984 — ELISA assay was developed which led to an appreciation of scope and
evolution of HIV epidemic.
• 1984- HLTV-III was given the name of HIV
PROBLEM STATEMENT
MORPHOLOGY OF HIV
IMMUNOPATHOGENESIS
Two major targets
•Immune system
•Central nervous system
Remain latent for many years
VIRAL LIFECYCLE
EPIDEMIOLOGICAL FEATURES
• 1) Agent factors:
• a) Agent (HIV)
• b) Reservoir of infection - cases and carriers
• c) Source of infection - virus has been found in greatest
concentration in blood ,semen and CSF.
2) Host factors:
a) Age - most cases have occurred among
sexually active persons aged 20—49 years.
• Plasma derived hepatitis B vaccine has not
been associated with transmission.
• The risk of getting infected with contaminated
needle, syringe or any other skin- piercing
instrument is lower than transfusion as risk
depends on "dose" of virus injected.
• c) Maternal-foetal transmission :
• HIV may pass from an infected mother to her foetus
through placenta or to her infant during delivery or
by breast feeding. If the mother has acute primary
infection during pregnancy, transmission rate is
higher due to high levels of viremia.
d) Occupational transmission of HIV (health care workers and lab
workers)
• Transmission usually occurs through contaminated hollow bore solid
needles with parental injury, other cuts, mucosal splashes, skin
contacts. Transmission through intact skin has not been documented.
• There is a small but definite risk of transmission in health care workers
and laboratory personnel who work with HIV containing materials
particularly sharp objects.
• There is a Lifetime risk to an orthopaedic surgeon.
• From HIV infection and later seroconversion - 0.01-12%.
• Seroconversion rate after single exposure of HCV -3-10%.
• Seroconversion rate after HBV - 30% (Hbe-Ag+ve) 60%(Hbc-Ag+ve)
• Risk of transmission from surgeon with HIV to patient is virtually non-
existent but significant with HBV and HCV.
• e) Transmission by other body fluids :
Evidence of transmission has been
demonstrated with cervicovaginal secretions
and breast—milk.
• Saliva which is grossly contaminated by blood
in bleeding gums can transmit HIV but is not
so common
CLASSIFICATION and DEFINITION
•The CDC classification system for HIV infected adolescents
and adults categories persons on basis of clinical conditions
associated with HIV infection and CD4 + T lymphocyte counts.
• Using this system, any HIV- infected individual with CD4+T
cell count < 200/mm3 has AIDS by definition regardless of
presence of symptoms or opportunistic diseases.
1993 revised classification system for HIV infection and AIDS
defining illness :
• CD4 +T lymphocyte categories
– Category 1 : 500cells/mm3
– Category 2 : 200-499 cells / mm3
– Category 3 : < 200 cells / mm3
CLINICAL CATEGORIES OF HIV INFECTION :
Category A : one or more of the following conditions, but no
conditions in B or C.
1. Asymptomatic HIV infection
2. Persistent generalized lymphadenopathy
3. Acute (primary) HIV infection with accompanying illness or
history of acute HIV infection.
Category B :
symptomatic conditions in an HIV infected adolescent or adult
that are not included in category C (AIDS - defining illnesses)
and that meet at least one of the following criteria
1) the conditions are attributed to HIV infection or are
indicative of a defect in cell mediated immunity or
2) the conditions are considered by physicians to have a
clinical course or to require management that is complicated
by HIV infection.
Examples of conditions in category B include, but are not
limited to
• Bacillary angiomatosis (Bartonella henselae, B. Quintana)
• Candidiasis, oropharyngeal (thrush)
• Candidiasis, vulvovaginal : persistent, frequent, or poorly responsive to
therapy.
• Cervical dysplasia (moderate or severe) / cervical carcinoma in situ
• Constitutional symptoms, such as fever or diarrhea lasting > 1 month
• Hairy leukoplakia, oral Herpes zoster (shingles) involving at least two
distinct episodes or more than one dermatome.
• Idiopathic thrombocytopenic purpura (ITP)
• Listeriosis
• Pelvic inflammatory disease, particularly if complicated by tubo—ovarian
abscess
• peripheral neuropathy.
Category C (AIDS) : includes the clinical conditions listed below (AIDS-
defining illnesses)
• Candidiasis of bronchi, trachea, or lungs
• Candidiasis, esophageal
• Cervical cancer, invasive
• Coccidioidomycosis, disseminated or extrapulmonary
• Cryptococcosis, extrapulmonary
• Cryptosporidiosis, chronic intestinal (> 1 month's duration)
Cytomegalovirus disease (other than liver, spleen, or nodes)
Cytomegalovirus retinitis (with loss of vision)
• Encephalopathy, HIV related
• Herpes simplex : chronic ulcers(> 1 month's duration), or bronchitis,
pneumonitis or esophagitis.
• Histoplasmosis, disseminated or extrapulmonary
• Isosporiasis, chronic intestinal (> 1 month's duration)
• Kaposi's sarcoma
• Lymphoma, Burkitt's (or equivalent term)
• Lymphoma, primary of brain
• Mycobacterium avium complex or M.kansasii, disseminated or
extrapulmonary
• Mycobacterium tuberculosis, any site (pulmonary or extrapulmonary)
Mycobacterium, other species or unidentified species, disseminated or o
extrapulmonary.
• Pneumocystis carinii pneumonia
• Pneumonia, recurrent
• Progressive multifocal leukoencephalopathy (PML)
• Salmonella septicemia, recurrent
• Toxoplasmosis of brain
• Wasting syndrome due to HIV
STAGING BY CD4 CELL COUNT:
• This is based on the CD4+ cell count as a measure of the degree of
destruction of the immune system.
CLINICAL MARKERS OF HIV DISEASE
PROGRESSION:
1. LYMPHADENOPATHY: involvement of two or more extrainguinal sites,
with discrete nodes larger than 1 cm in diameter. Adenopathy is not a
reliable marker, because only about 50% of patients with early stage
disease develop it.
2. THROMBOCYTOPENIA: develops in as many as 10% of early—stage HIV
patients. It has been shown that the CD4+ T cell count correlates with
thrombocytopenia.
3. ORAL CANDIDIASIS: is a reasonable marker for early symptomatic disease
but is not useful for differentiation of early stage patients.
4. CONSTITUTIONAL SYMPTOMS: (weight loss, fever, anorexia) are generally
useful only in that they signal the period just prior to late stage disease.
DEFINITION OF AIDS WHO
• Adults : AIDS in an adult is defined by the existence of at least two of the
major signs
• associated with atleast one minor sign in the absence of known cause of
immunosuppression
• such as cancer or severe malnutrition or other recognized causes.
• Major signs:
– Weight loss greater than 10 percent of body weight, chronic diarrhoea for more than 1
month, prolonged fever for more than 1 month (intermittent or constant).
• Minor signs:
– 1) Persistent cough for more than 1 month
– 2) Generalized pruritic dermatitis
– 3) Recurrent herpes zoster infection
– 4) Oropharyngeal candidiasis
– 5) Chronic progressive and disseminated herpes simplex virus infections
– 6) Generalized lymphadenopathy
• The presence of generalized Kaposi’s sarcoma or cryptococcal meningitis
is sufficient for the diagnosis.
EXPANDED WHO CASE DEFINITION FOR
AIDS SURVEILLANCE :
• A person is considered to have AIDS if a test for HIV antibody is positive
and one or more of following conditions are present:
1. > 10% body weight loss or cachexia with diarrhoea or fever or both,
intermittent or constant for at least 1 month, not known to be due to a
condition unrelated to HIV infection.
2. Cryptococcal meningitis
3. Pulmonary or extra-pulmonary TB.
4. Kaposi sarcoma
5. Neurological impairment sufficient to prevent independent daily activities not
known to be due to a condition unrelated to HIV infection.
6. Candidiasis of oesophagus
7. Clinically diagnosed life threatening or recurrent episodes of pneumonia, with
or without aetiological confirmation.
8. Invasive cervical cancer.
REVISED WORLD HEALTH ORGANIZATION (WHO) CLINICAL
STAGING OF HIV/AIDS FOR ADULTS AND ADOLESCENTS (2005)
• Primary HIV infection
• Asymptomatic
• Acute retroviral syndrome
• Clinical stage 1
• Asymptomatic
• Persistent generalized lymphadenopathy
• Clinical stage 2
• Moderate and unexplained weight loss (<10% of presumed or measured body weight)
• Recurrent respiratory tract infections (such as sinusitis, bronchitis, otitis media, pharyngitis)
• Herpes zoster
• Recurrent oral ulcerations
• Papular pruritic eruptions
• Angular cheilitis
• Seborrhoeic dermatitis
• Onychomycosis (fungal nail infections)
• Clinical stage 3
• Conditions where a presumptive diagnosis can be made on the basis of clinical
signs or simple investigations
• Unexplained chronic diarrhoea for longer than one month
• Unexplained persistent fever (intermittent or constant for longer than one month)
• Severe weight loss (>10% of presumed or measured body weight)
• Oral candidiasis
• Oral hairy leukoplakia
• Pulmonary tuberculosis (TB) diagnosed in last two years
• Severe presumed bacterial infections (e.g. pneumonia, empyema, meningitis,
bacteraemia, pyomyositis, bone or joint infection)
• Acute necrotizing ulcerative stomatitis, gingivitis or periodontitis
• Conditions where confirmatory diagnostic testing is necessary
• Unexplained anaemia (< 80 g/l), and or neutropenia (<500/µl) and or
thrombocytopenia (<50 000/ µl) for more than one month
• Clinical stage 4
• Conditions where a presumptive diagnosis can be made on the basis of clinical
signs or simple investigations
• HIV wasting syndrome
• Pneumocystis pneumonia
• Recurrent severe or radiological bacterial pneumonia
• Chronic herpes simplex infection (orolabial, genital or anorectal of more than one
month's duration)
• Esophageal candidiasis
• Extrapulmonary tuberculosis
• Kaposi's sarcoma
• Central nervous system toxoplasmosis
• HIV encephalopathy
• Conditions where confirmatory diagnostic testing is necessary
• Extrapulmonary cryptococcosis including meningitis
• Disseminated non-tuberculous mycobacteria infection
• Progressive multifocal leukoencephalopathy
• Candida of trachea, bronchi or lungs
• Cryptosporidiosis
• Isosporiasis
• Visceral herpes simplex infection
• Cytomegalovirus (CMV) infection (retinitis or of an organ other than liver, spleen
or lymph nodes)
• Any disseminated mycosis (e.g. histoplasmosis, coccidiomycosis, penicilliosis)
• Recurrent non-typhoidal salmonella septicaemia
• Lymphoma (cerebral or B cell non-Hodgkin)
• Invasive cervical carcinoma
• Visceral leishmaniasis
CLINICAL MANIFESTATIONS
• Clinical features are classified into 4 major categories :
• 1) Initial infection with virus and development of antibodies
• 2) Asymptomatic carrier stage
• 3) AIDS - related complex (ARC)
• 4) AIDS
1. Initial infection: Most HIV infected persons have only mild illness (fever, sore-
throat and rash) which they experience a few weeks after initial infection. They
have these symptoms for first 5 years or so. HIV antibodies take between 2-12
weeks to appear in blood stream. The period before antibodies is "window
period". During this period, infected individual will test negative on standard
antibody blood test.
2. Asymptomatic carrier stage: Infected people have antibodies, but no overt signs
of disease, except generalized lymphadenopathy is present.
3. AIDS related complex (ARC): Here damage to immune system occurs but without
opportunistic infections and cancers associated with AIDS. Patients show clinical
signs like unexplained diarrheoa lasting longer than a month, malaise, fatigue, loss
of more than 10% body weight, fever, night sweats.
4. AIDS: is the end stage of 'HIV infection. A number of opportunistic infections
occur. Death is due to uncontrolled infection.
MUSCULOSKELETAL MANIFESTATIONS IN HIV INFECTED
PATIENTS
• Principles to keep in mind when evaluating an HIV infected patient with
musculoskeletal syndrome include :
1. Any musculoskeletal syndrome in non-HIV infected patients can occur in
HIV infected.
2. HIV infection can alter clinical presentation and course may be more
severe in presentation.
3. Early diagnosis of infections is important to prevent spread in an
immunocompromised patients.
REACTIVE ARTHRITIS
• Reactive arthritis: refers to acute non-purulent arthritis complicating an
infection elsewhere in the body.
• HIV virus associated arthropathy is not associated with extra-articular
infections or HLA-B-27.
• Outside the setting of HIV infection, reactive arthritis occurs
predominantly in individuals who have inherited B27 gene, in most series
in which shigella, yersinia or clamydia are the triggering agents.
• Clinical features:
• Arthritis is usually asymmetric with involvement of new joints occurring
over a period of few days to 1-2 weeks.
• Reactive arthritis usually occurs in foot and ankle.
• The joints of lower extremities especially knee, ankle, and subtalar,
metatarsophalangeal and toe interphalangeal joints are the most
common sites.
• Tendinitis and fascitis produce pain at multiple insertion sites (enthesitis)
especially Achilles insertion, plantar fascia and anterior and posterior
tibial tendons.
• Dactylitis or "sausage digit" a diffuse swelling of solitary finger or toe is a
distinctive feature of reactive arthritis.
• Cutaneous symptoms include psoriasiform rashes, keratoderma
blenorrhagia onychodystr0phy and oral ulcers.
• Ocular disease includes conjunctivitis and anterior uveitis.
• Laboratory findings :
– ESR is elevated and mild anaemia may be present
• Treatment :
– acute arthritis or tendinitis may benefit from local
injection of corticosteroids.Patients may need
long-term NSAIDS and analgesic therapy.
REITER'S SYNDROME
• Reiter’s syndrome is classical triad of arthritis, urethritis and
conjunctivitis.
• It was the first rheumatic syndrome reported in patients with
HIV infection.
• Arthritis remains active and may increase in severity as HIV
disease progresses.
• Between 63 and 75% of HIV patients with reiter's syndrome
have HLA-B27 cell surface antigen.
• Pathogenesis :
• The pathogenesis of HIV related Reiter's disease includes :
• Decreased CD4 + lymphocytes –
• Increased CD8 + cytotoxic lymphocyte
• Induction by infectious agents
• Enteric organisms like shigella, flexneri, salmonella, c.jejuni and
yersinia enterocolitica etc are the cause of infection in HIV associated
Reiter's syndrome.
• Clinical features :
– the lower extremities are mainly involved
– Typical involvement is assymetrical and polyarticular, rarely symmetrical.
– One knee joint is almost always affected.
– Oligoarthritis of large weight bearing joints (usually ankles or knees)
– Enthesopathy may involve achilles tendon, plantar fascia, anterior and
posterior tibial tendons and tendons of the feet.
– Frank synovitis may occur at ankle and subtalar, metatarsophalangeal and
interphalangeal joints of feet.
– Multidigit dactylitis, especially in upper extremities.
– Synovitis of wrist, elbow and shoulder may lead to contracture and joint
fusion but is not common.
– Enthesopathy may occur at medial and lateral epicondylar, rotator cuff or
flexor tendons of the digits.
• Urinary tract involvement: acute non-specific urethritis.
• Ocular involvement: Mild conjunctivitis and iritis
• Mucocutaneous lesions : superficial ulcerations of mouth occur.Subungual
hyperkeratotic lesions elevate and may separate nails.
• x-ray findings :
• Early, in mild arthritis, slight soft—tissue thickening and minimal subchondral
osteoporosis may be seen.
• Later, subchondral osteoporosis becomes pronounced and joint space narrows.
• Finally, destructive changes may lead to ankylosis.
• Peripheral joints:
• Destructive changes about the interphalangeal and metatarso phalangeal joints of
toes and knee and ankle, subluxation and lateral deviation of toes seen.
• Occasionally ankylosis of small joints occurs.
• Laboratory findings :
 Normal synovial fluid compartment level
 Negative tests for rheumatoid factor
 Positive HLA-B27 antigen
 Positive stool cultures for shigella, yersinia and salmonella
• Differential diagnosis :
 Reiter's disease is differentiated from rheumatoid arthritis by lack of
rheumatoid factor and antinuclear antibody.
• Treatment:
• NSAID's like indomethacin (50mg 3 times / day provide relief for enthesopathy).
• Phenylbutazone (100mg 2 to 3 times / day) is quite useful in HIV associated
reiter's syndrome and should be given in early course of disease.
• Sufasalazine has been effective as a second line therapy (lg to 3 g/ day). Sulfa
allergy is common in HIV infected patients and may limit the use of sulfa drugs.
• Methotrexate, other immunosuppressive agents and phototherapy should be
used only with ; extreme caution, associated with sudden fulminate
immunodeficiency characterized by the appearance of Kaposi's sarcoma and
severe and sometimes fatal opportunistic infections in patients who are HIV
infected and have Reiter's syndrome.
• Intraarticular corticosteroid injections usually provide effective symptomatic
control. The benefits of corticosteroid injections can be augmented by
immobilizing the affected joint in a splint for 5 to 7 days after the injection
• Orthopaedic treatment:
• Aims to prevent deformity and preservation of mobility. The patient is placed at
bed rest and weight bearing is forbidden.
• NSAID's are prescribed and splint applied and removed at intervals for exercises
and application of hot packs.
PSORIASIS AND PSORIATIC -LIKE ARTHRITIS
• The incidence of psoriatic arthritis in HIV infected individual is 2-3%. Patients with
HIV infection and psoriatic arthritis fall into one of two patterns of disease.
• The articular disease is sustained and aggressive, progressing to joint erosions.
• Characterized by mild and intermittent joint involvement.
• Clinical manifestations :
• Most common sites of involvement are the foot and the ankle.
• There is severe enthesopathy and dactylitis, especially in the feet which may lead
to deformities.
• Frank synovitis and synovial effusions can occur at ankle, subtalar, metatarso—
phalangeal and interphalangeal joints of the feet.
• The radiological appearance of these joints may mimic classic psoriatic arthritis
with "pencil in cup" deformity, osteolysis of phalangeal and metacarpal bone,
small joint ankylosis and marginal erosions.
• Presence of skin changes is essential for diagnosis of psoriasis. Small patches on
extensor surfaces of elbows or knees or scalp may be found.
• Nail involvement occurs in distal interphalangeal joints of hands and feet. Nail
involvement with pitting, ridging and subangual-hyperkeratosis is necessary for
diagnosis.
PENCIL IN CUP
TREATMENT:
• NSAID'S such as indomethacin (75 mg to 150mg /day) can be
used for joint symptoms.
• Retinoic acid derivatives
• Psoralen plus ultraviolet light (PUVA)
• Low doses of methotrexate (15-75mg/week) has led to rapid
(< 4 weeks) improvement in inflammatory joint symptoms as
well as improvement in skin lesions. Methotrexate can be
given until skin and joint disease is under control, then slowly
tapered aiming for a maintenance dose of 5mg/week.Patients
must be monitored closely,because there are reports of
immunodeficiency and Opportunistic infections in HIV
infected individuals who are treated with methotrexate.
• Intra-articular steroid injection (every 4-6 months) may
provide relief.
SEPTIC ARTHRITIS
• Septic arthritis is an acute arthritis due to Specific bacteria and productive of
purulent exudate. Septic arthritis occurs more commonly in intravenous drug
abusers and hemophiliacs who are HIV infected.
• Most common pathogens:
• Staphyloccus aureus and streptococcus pneumoniae
• In advanced HIV infected patients — gonococcus, sporothrix, haemophillus
influenzae, salmonella, Candida.
• Mode of infection: hematogenous from an infective focus, (soft tissue or bone
infection)
• Clinical features: Joints affected are knees, shoulder and hip. In drug abusers, S.I
joint, symphysis pubis, strenoclavicular and intervertebral discs are also involved.
– Usually, one joint is involved which is swollen, red warm and tender.
– Pain accentuated by joint movement and increases in intensity over several hours.
– Patient limps if lower extremity involved.
• Laboratory findings: aspirated joint is serous, serosanguineous or frankly purulent.
High leukocytosis and positive C-reactive protein.
• Radiographic features reveal osteopenia and joint effusion.
• Treatment:
– Drainage: in suppurative joint disease immediate and free
drainage is mandatory.
– Antibiotics: penicillin or a cephalosporin may be combined
with an aminoglycoside which is effective against gram
positive and gram negative organisms.
– Immobilization: limb is immobilized in a removable splint
and is elevated. The limb is slowly mobilized in subacute
subsiding stage to prevent ankylosing adhesions.
– Differential diagnosis: septic arthritis can be difficult to
differentiate from reactive arthritis but culture of blood
and synovial fluid is sterile in case of reactive arthritis.
HIV ASSOCIATED ARTHROPATHY
• HIV infected individuals experience a variety of joint problems
without obvious caused that are referred to as HIV or AIDS
associated arthropathy.
• This syndrome is characterized by subacute, oligoarticular
arthritis developing over a period of 1 to 6 weeks and lasting
6 weeks to 6 months.
• It generally involves the large joints, mainly the knees and
ankles and is non-erosive with only mild inflammatory
response.
• X-ray of joints are non-revealing.
• NSAIDS are marginally helpful. Relief has been noted with the
use of intraarticular glucocorticoids.
PAINFUL ARTICULAR SYNDROME
• A second form of arthritis also thought to be
secondary to HIV infection. This syndrome
occurs due to direct effect of HIV on the joint.
• This condition is found in 10% of AIDS
patients. It affects primarily knees, shoulders
and elbows and lasts for 2 to 24 hours.
Presents as acute severe sharp pain in
affected joints.
• Narcotic analgesics help in severe cases.
OSTEOMYELITIS
• The commonest cause of radiologically demonstrable bone lesions is
infection . A large number of reports exist describing osteo- myelitis
affecting unusual sites and involving unusual organisms.
• The commonest sites are spine and long bones,followed by chest wall and
clavicles .
• Normally pathogenic bacteria, Staphylococcus aureus and Salmonella
spp., are the most frequently encountered.
• Others such as Cryptococcus neoformans, MTB, Histoplasma capsulatum,
Nocardia asteroides and Mycobacterium avium complex (MAC) have been
described.
• Involvement of the spine, sacrum or sacroiliac joints should suggest MTB
infection . Involvement with Actinomyces sp., or less commonly Candida
albicans, causes rib destruction and a chest wall mass.
•The radiographic findings are as for osteomyelitis in
the general population.
–MRI shows a focus of fluid within the bone marrow,
perhaps breaching the cortex, and usually extensive bone
marrow oedema often affecting the entire length of the
bone. Periostitis is typical on all modalities.
–CT is useful for demonstrating the densely calcified
sequestrum.
•Treatment is with appropriate antibiotics and
occasionally surgical debridement. Response to
treatment is poorer in immuno- compromised
patients.
MYOSITIS
•Infectious myositis, also called pyomyositis or tropical
myositis, was a rare diagnosis in temperate climates prior to
the HIV era. Infectious myositis presents subacutely over two
to three weeks; three phases have been described.
•The initial invasive phase is marked by local tenderness and
mild swelling of the involved muscle, and occasionally with
low-grade fevers. After one to three weeks, a purulent phase
develops, with painful induration, edema, local rise of
temperature without erythema, and systemic fevers.
•Most patients present during this phase and may have
leukocytosis and an elevated sedimentation rate, but CK
levels are usually surprisingly low. Blood cultures are rarely
positive at this stage.
•MRI is the most sensitive diagnostic tool, but
ultrasound and CT scanning will also reveal a
purulent abscess in the involved muscle; occasionally
more than one muscle is involved.
•Left untreated, a third disseminated phase ensues,
with septic shock and associated morbidity.
•S.aureus, streptococcus pyogens, Cryptococcus
neoformans, M.tuberculosis are the organisms
responsible.
Clinical features :
• In first stage, Patients present with pain localized to one muscle group and
with low grade fever. Here aspiration does not reveal pus.
• In second (suppurative stage), pain, fever and oedema of affected muscle
present. Here aspiration reveals pus.
• Third stage, is diagnosed when patient appears septic. A fluctuant abscess
is noted and entire muscle may be necrotic.
• Treatment : Small abscess can be cured by systemic antibiotics but
multiple or large abscesses need surgical incision and drainage.
IDIOPATHIC POLYMYOSITIS
• Polymyositis is the term applied to a group of idiopathic disorders
characterized pathologically by degenerative and inflammatory changes of
skeletal muscle and clinically by severe muscle weakness chiefly affecting
proximal muscle groups about the pelvic and shoulder girdles, the anterior
neck muscles and often muscles of deglutition.
• Progressive proximal weakness of lower and upper extremities (less
common) is the most frequent complaint.
• Distal weakness is mild and rare.
• Muscle pain, bilateral and symmetrical, involving shoulder and upper arm
is present in most patients.
• Dysphagia is a prominent feature at the onset in one fourth of patients.
• Upper limb contractures occur in 10% of patients and involve elbows and
fingers.
• There is increasing difficulty in rising from a chair, walking up stairs and
using arms for any length of time.
• The dose of prednisolone is gradually tapered when the
serum enzymes return to normal.
• Maintenance dose of 5mg-15mg/day is reached depending on
clinical response. This dose is required to prevent further
worsening of muscle weakness and elevation of muscle
enzymes.
• Immunosuppressive agents:
– steroid resistant cases are tried with immunosuppressive agents like
methotrexate and azathioprine.
• Orthopaedic treatment:
– during early stage, warm, moist pack applied.
– Gentle passive range of motion exercises.
– Splints to prevent deformities
SOME OTHER MUSCULOSKELETAL
MANIFESTATIONS OF HIV
• Bursitis:
– Septic bursitis is a well described entity in immunocompromised patients.
– S. aureus is the most common etiologic agent.
– Infection localizes to olecrenon, prepatellar and less frequently, subdeltoid bursae.
• Kaposis sarcoma :
– Is a multifocal spindle cell neoplasm.
– Most common neoplasm in HIV infected patients.
– Patients present with bone pain.
– X-ray reveals cortical erosion, osseous destruction and periosteal reaction.
• Avascular necrosis:
– HIV induced vasculitis has been postulated as a cause.
– Affects any joint, mainly hip.
– Joint pain is the complaint
– X-ray shows patchy sclerosis, collapse and secondary degenerative disease.
• Fibromyalgia:
– Occurs in I.V drug users who are HIV positive
– It is characterized by widespread musculoskeletal pain, stiffness, paresthesia, disturbed sleep, easy
fatigability, dizziness, depression and loss of short-term memory.
– Multiple, painful tender points which are symmetrically distributed.
– NSAIDs and antidepressants help.
MANIFESTATIONS OF DRUG TOXICITY
A. AZT associated myositis
a) Drug allergies are the most significant allergic reactions occurring in HIV—infected
patients and appear to become more common as the disease
progresses.Idiosyncratic reactions to AZT include muscular weakness and elevated
CPK levels. Patients showing muscular symptoms have a subacute onset of myalgia,
proximal weakness and muscle tenderness.Muscle biopsy shows myofibril necrosis
and associated inflammation.Electromyograms show myopathic changes.
b) Treatment : prednisolone (lmg/kg/day for 10-14 days) can be given for muscle pain,
weakness and elevated CPK levels. As CPK levels normalize and symptoms
resolve,prednisolone can be tapered off gradually.
c) Another antiretroviral agent can be used if clinically indicated.
d) If CPK levels are mildly elevated, but there are no clinical symptoms, patient can
choose to continue with AZT therapy or to switch to another antertroviral agent.
B. Drug allergies, also occur with TMP/SMX.
A. TMP/SMX are used for treatment of PCP.These reactions are characterized by
erythematous, morbilliform eruption that are pruritic, and often associated with fever.
C. With abacavir (nucleoside analogue) hypersensitivity reaction has been
noted.
RISKS AND PREVENTION
• Emanuel described three factors that must be known to calculate the
orthopaedic surgeon's risk of occurring HIV from punctures in operating
room: -
– Frequency of punctures
– Percentage of surgical patients who are HIV positive
– Risk of HIV transmission per needlestick from known HIV-positive Patients.
• Risk increases with increased viral load of patient, quantity of blood
injected and depth of inoculation.
• The risk of transmission per needle stick is around 0.3% as estimated by
CDC.
• Annual risk to the orthopaedic surgeon is between 0.025% 0.5% according
to CDC.
• Prevention :
• The surgeon should know the causes, associated diseases
affecting musculosketal system, risks of transmission and
precautions to be taken.
• The guidelines for surgery should include assessment of HIV—
positive patient's immune status, including CD4 lymphocyte
count, history of opportunistic infection, and state of
nutrition and general health.
• In the absence of an effective means of prophylaxis, chief
defence, against HIV infection is prevention of transmission.
• Lacerations from bone fragments and edges, as well as cuts
and needle sticks must be avoided.
AAOS RECOMMENDATIONS FOR OPERATING
ROOM PROCEDURES
1. Avoid use of sharp instruments if possible.
2. Avoid direct passing of sharp instruments between team members.
3. Use notouch technique
4. Use a scalpel for skin incisions only, then scissors and electrocautery
5. Avoid simultaneous suture of same layer by two members of a team
6. Prefer to use blunt suture needles
7. Avoid hasty gestures
8. Comply with regulations for elimination of disposable material
9. Always wear gloves when handling material covered with blood.
UNIVERSAL PRECAUTIONS
• The initial CDC recommendations called for blood and body fluid precautions when a patient
was known or suspected to be infected with blood borne pathogens. The CDC called for
precautions to be consistently used all the time regardless of apparent blood borne infection
status of a given patient. These universal precautions are intended to prevent parenteral,
mucous membrane, and nonintact skin exposures of health care workers to blood- bome
pathogens.
– During a surgical operation, when an overt sharp injury occurs, the aseptic barrier is broken, injured
worker leaves the operating field and returns on the reestablishment of asepsis.
• With double gloving, such gross contamination is reduced. Double gloving technique reduces
risk of blood contact from 29% to 18% however gloves must be changed every 2 hours or
every hour for trauma cases.
– Greater than half of needle-stick injuries occurred to index finger of non—dominant hand. There
should be additional re-inforcement to this portion of glove on routine use.
– Glasses/transparent shields should be worn to prevent contact of blood to eyes during operations.
– Sharp objects should be passed in trays to avoid accidental pricks .Due to high prevalence of HBV
infection in HIV infected individuals, all health care workers and surgeons dealing with HIV infected
patients should be immunized with HBV vaccine.
• The success of universal precautions is limited. Gloves do not prevent needle-stick or other
penetrating sharp injuries, and gloves certainly can tear. Latex gloves appear preferable to
vinyl as rates of perforation in latex gloves is much lower than polyvinyl chloride gloves.
LABORATORY DIAGNOSIS OF HIV
CAUSES OF FALSE-POSITIVE AND FALSE-NEGATIVE REACTIONS IN
ENZYME IMMUNOSAYS FOR ANTIBODY TO HIV
• Antibodies against HLA
• Passive immunization with HIV antibody-positive immunoglobulin
• Alcoholic liver disease
• Lymphoma .
• Influenza immunization
• Acute viral infection
• Chronic renal disease Stevens-Johnson syndrome
• Conditions that have been associated with false-negative tests
• Acute HIV infection-seroconversion usually occurs within 3-6 months;
antibody testing may be negative during this window period
• lmmunosuppressive therapy
• Immune deficiency (B—cell defects)
• Rheumatoid factor
• Late-stage AIDS
• Exchange transfusion
• Different assay systems
CONTROL OF AIDS
• 1) Prevention
– a) Education : People should be educated on AIDS, its nature, transmission and
prevention.
– b) Prevention of blood-borne transmission.
• All blood should be screened for HIV-1 and HIV-2 before transmission. Strict sterilizing practices should be
ensured in hospitals and clinics.
• 2) Antiretroviral treatment: Antiviral chemotherapy has proved to be useful in
prolonging life of ill patients.
• 3) Specific prophylaxis : Here manifestations of AIDS are treated.
– Primary prophylaxis against P carinii -pneumonia with CD4 count below 200 cells/(j.L ‘
• Trimethoprim-sulfamethoxazole, lDS/day pentamidine (300mg /month) and dapsone (100mg/day) '
• M. Avium complex - Rifabutin (300mg/day)
• Prophylaxis against M. tuberculosis
• INH 300 mg daily for 9 months to 1 years + pyridoxine 25-50mg/day
• 4) Primary health care - AIDS touches all aspects of primary health care
including mother and child health, family planning and education.
POST-EXPOSURE PROPHYLACTIC TREATMENT
• After the exposure of health care workers to HIV infected blood,
chemoprophylaxis is offered.
• This treatment is started within 2 hours of exposure and generally
recommended for at least a 4 week course.
• The following treatment is recommended by the US centre for disease
control and prevention:
• a) Double combination of treatment with
– - AZT (200 mg 3 times daily + Lamivudine (3TC) (150 mg twice daily) for 4 weeks
• b) If “source” individual has advanced A1 3.
– Protease inhibitor (nelflnavir) (750 mg 3 times daily) should be added to the AZT/3TC
regimen'
• e) If “source” individual has failed on AZT/3TC therapy Stavudine (d4t)
plus ddl should be used
CONCLUSION
• Epidemiologic and laboratory observations
suggest that HIV infection is transmitted through
intimate sexual contact or through parenteral
contact with blood or blood products. It also
appears likely that this retrovirus produces a
spectrum of disease ranging from subclinical to
fatal. A better understanding of epidemiology of
AIDS will aid in designing better prevention
strategies. Health care workers and others should
familiarize themselves with, and follow, the
recommended precautions when handling
specimens, secretions and excretions of persons
known to be infected with the virus.
REFERENCES :
• Harisson's principles of internal medicine - 17th edition.
• PSM textbook - Park
• Robbin's pathologic basis of disease – 8thedition
• Orthopaedics principles and their application - Turek, 4th
edition
• Campbell's operative orthopaedics - 11th edition
• Mercer's Orthopaedic surgery
• Radiologic clinics of North America Medical clinical of North
America.
THANK YOU

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Skeletal manifestations in hiv

  • 1. SKELETAL MANIFESTATIONS IN HIV Presentor: Dr.Pavan kumar Moderator: Dr. Prashant Sir Head of orthopaedics department: Dr. Nagendra babu sir
  • 2. TOPICS • INTRODUCTION –HISTORY –PROBLEM STATEMENT –MORPHOLOGY OF HIV –IMMUNOPATHOGENESIS –VIRAL LIFECYCLE • EPIDEMIOLOGICAL FEATURES • CLASSIFICATION and DEFINITION –CDC CLASSIFICATION AND DEFINITION –STAGING BY CD4 CELL COUNT CLINICAL MARKERS OF HIV DISEASE PROGRESSION –WHO DEFINITION OF AIDS –EXPANDED WHO CASE DEFINITION FOR AIDS SURVEILLANCE –WORLD HEALTH ORGANIZATION STAGING OF HIV/AIDS • CLINICAL MANIFESTATIONS • MUSCULOSKELETAL MANIFESTATIONS IN HIV INFECTED PATIENTS –REACTIVE ARTHRITIS –REITER'S SYNDROME –PSORIASIS AND PSORIATIC LIKE ARTHRITIS –SEPTIC ARTHRITIS –HIV ASSOCIATED ARTHROPATHY –PAINFUL ARTICULAR SYNDROME –OSTEOMYELITIS –MYOSITIS –IDIOPATHIC POLYMYOSITIS –OTHER MUSCULOSKELETAL MANIFESTATIONS OF HIV –MANIFESTATIONS OF DRUG TOXICITY • RISKS AND PREVENTION –AAOS RECOMMENDATIONS FOR OPERATING ROOM PROCEDURES –UNIVERSAL PRECAUTIONS –LABORATORY DIAGNOSIS OF HIV –CAUSES OF FALSE-POSITIVE AND FALSE- NEGATIVE REACTIONS IN ENZYME IMMUNOSAYS FOR ANTIBODY TO HIV –CONTROL OF AIDS –POST-EXPOSURE PROPHYLACTIC TREATMENT • CONCLUSION • REFERENCES
  • 3. HISTORY • AIDS was first recognized in USA in the summer of 1981 by CDC which reported unexplained occurrence of pneumocystitis pneumonia in a cohort of homosexual men. Within months disease became recognized among male and female IV drug users and soon thereafter in recipients of blood transfusion and in haemophiliacs. After the diagnosis of AIDS, the human immunodeficiency Virus was identified and was found to cause this disease. • I983 - Pastuer institute in Paris isolated a retrovirus from a patient with persistent lymphadenopathy and was called lymphadenopathy associated virus (LAV). • 1984 - It was named HTLV—III by Gallo and it was proved to be the causative agent. • 1984 — ELISA assay was developed which led to an appreciation of scope and evolution of HIV epidemic. • 1984- HLTV-III was given the name of HIV
  • 5.
  • 7. IMMUNOPATHOGENESIS Two major targets •Immune system •Central nervous system Remain latent for many years
  • 9.
  • 10.
  • 11. EPIDEMIOLOGICAL FEATURES • 1) Agent factors: • a) Agent (HIV) • b) Reservoir of infection - cases and carriers • c) Source of infection - virus has been found in greatest concentration in blood ,semen and CSF.
  • 12. 2) Host factors: a) Age - most cases have occurred among sexually active persons aged 20—49 years. • Plasma derived hepatitis B vaccine has not been associated with transmission. • The risk of getting infected with contaminated needle, syringe or any other skin- piercing instrument is lower than transfusion as risk depends on "dose" of virus injected.
  • 13. • c) Maternal-foetal transmission : • HIV may pass from an infected mother to her foetus through placenta or to her infant during delivery or by breast feeding. If the mother has acute primary infection during pregnancy, transmission rate is higher due to high levels of viremia.
  • 14. d) Occupational transmission of HIV (health care workers and lab workers) • Transmission usually occurs through contaminated hollow bore solid needles with parental injury, other cuts, mucosal splashes, skin contacts. Transmission through intact skin has not been documented. • There is a small but definite risk of transmission in health care workers and laboratory personnel who work with HIV containing materials particularly sharp objects. • There is a Lifetime risk to an orthopaedic surgeon. • From HIV infection and later seroconversion - 0.01-12%. • Seroconversion rate after single exposure of HCV -3-10%. • Seroconversion rate after HBV - 30% (Hbe-Ag+ve) 60%(Hbc-Ag+ve) • Risk of transmission from surgeon with HIV to patient is virtually non- existent but significant with HBV and HCV.
  • 15. • e) Transmission by other body fluids : Evidence of transmission has been demonstrated with cervicovaginal secretions and breast—milk. • Saliva which is grossly contaminated by blood in bleeding gums can transmit HIV but is not so common
  • 16. CLASSIFICATION and DEFINITION •The CDC classification system for HIV infected adolescents and adults categories persons on basis of clinical conditions associated with HIV infection and CD4 + T lymphocyte counts. • Using this system, any HIV- infected individual with CD4+T cell count < 200/mm3 has AIDS by definition regardless of presence of symptoms or opportunistic diseases. 1993 revised classification system for HIV infection and AIDS defining illness : • CD4 +T lymphocyte categories – Category 1 : 500cells/mm3 – Category 2 : 200-499 cells / mm3 – Category 3 : < 200 cells / mm3
  • 17. CLINICAL CATEGORIES OF HIV INFECTION : Category A : one or more of the following conditions, but no conditions in B or C. 1. Asymptomatic HIV infection 2. Persistent generalized lymphadenopathy 3. Acute (primary) HIV infection with accompanying illness or history of acute HIV infection.
  • 18. Category B : symptomatic conditions in an HIV infected adolescent or adult that are not included in category C (AIDS - defining illnesses) and that meet at least one of the following criteria 1) the conditions are attributed to HIV infection or are indicative of a defect in cell mediated immunity or 2) the conditions are considered by physicians to have a clinical course or to require management that is complicated by HIV infection. Examples of conditions in category B include, but are not limited to
  • 19. • Bacillary angiomatosis (Bartonella henselae, B. Quintana) • Candidiasis, oropharyngeal (thrush) • Candidiasis, vulvovaginal : persistent, frequent, or poorly responsive to therapy. • Cervical dysplasia (moderate or severe) / cervical carcinoma in situ • Constitutional symptoms, such as fever or diarrhea lasting > 1 month • Hairy leukoplakia, oral Herpes zoster (shingles) involving at least two distinct episodes or more than one dermatome. • Idiopathic thrombocytopenic purpura (ITP) • Listeriosis • Pelvic inflammatory disease, particularly if complicated by tubo—ovarian abscess • peripheral neuropathy.
  • 20. Category C (AIDS) : includes the clinical conditions listed below (AIDS- defining illnesses) • Candidiasis of bronchi, trachea, or lungs • Candidiasis, esophageal • Cervical cancer, invasive • Coccidioidomycosis, disseminated or extrapulmonary • Cryptococcosis, extrapulmonary • Cryptosporidiosis, chronic intestinal (> 1 month's duration) Cytomegalovirus disease (other than liver, spleen, or nodes) Cytomegalovirus retinitis (with loss of vision) • Encephalopathy, HIV related • Herpes simplex : chronic ulcers(> 1 month's duration), or bronchitis, pneumonitis or esophagitis. • Histoplasmosis, disseminated or extrapulmonary • Isosporiasis, chronic intestinal (> 1 month's duration)
  • 21. • Kaposi's sarcoma • Lymphoma, Burkitt's (or equivalent term) • Lymphoma, primary of brain • Mycobacterium avium complex or M.kansasii, disseminated or extrapulmonary • Mycobacterium tuberculosis, any site (pulmonary or extrapulmonary) Mycobacterium, other species or unidentified species, disseminated or o extrapulmonary. • Pneumocystis carinii pneumonia • Pneumonia, recurrent • Progressive multifocal leukoencephalopathy (PML) • Salmonella septicemia, recurrent • Toxoplasmosis of brain • Wasting syndrome due to HIV
  • 22. STAGING BY CD4 CELL COUNT: • This is based on the CD4+ cell count as a measure of the degree of destruction of the immune system.
  • 23. CLINICAL MARKERS OF HIV DISEASE PROGRESSION: 1. LYMPHADENOPATHY: involvement of two or more extrainguinal sites, with discrete nodes larger than 1 cm in diameter. Adenopathy is not a reliable marker, because only about 50% of patients with early stage disease develop it. 2. THROMBOCYTOPENIA: develops in as many as 10% of early—stage HIV patients. It has been shown that the CD4+ T cell count correlates with thrombocytopenia. 3. ORAL CANDIDIASIS: is a reasonable marker for early symptomatic disease but is not useful for differentiation of early stage patients. 4. CONSTITUTIONAL SYMPTOMS: (weight loss, fever, anorexia) are generally useful only in that they signal the period just prior to late stage disease.
  • 24. DEFINITION OF AIDS WHO • Adults : AIDS in an adult is defined by the existence of at least two of the major signs • associated with atleast one minor sign in the absence of known cause of immunosuppression • such as cancer or severe malnutrition or other recognized causes.
  • 25. • Major signs: – Weight loss greater than 10 percent of body weight, chronic diarrhoea for more than 1 month, prolonged fever for more than 1 month (intermittent or constant). • Minor signs: – 1) Persistent cough for more than 1 month – 2) Generalized pruritic dermatitis – 3) Recurrent herpes zoster infection – 4) Oropharyngeal candidiasis – 5) Chronic progressive and disseminated herpes simplex virus infections – 6) Generalized lymphadenopathy • The presence of generalized Kaposi’s sarcoma or cryptococcal meningitis is sufficient for the diagnosis.
  • 26. EXPANDED WHO CASE DEFINITION FOR AIDS SURVEILLANCE : • A person is considered to have AIDS if a test for HIV antibody is positive and one or more of following conditions are present: 1. > 10% body weight loss or cachexia with diarrhoea or fever or both, intermittent or constant for at least 1 month, not known to be due to a condition unrelated to HIV infection. 2. Cryptococcal meningitis 3. Pulmonary or extra-pulmonary TB. 4. Kaposi sarcoma 5. Neurological impairment sufficient to prevent independent daily activities not known to be due to a condition unrelated to HIV infection. 6. Candidiasis of oesophagus 7. Clinically diagnosed life threatening or recurrent episodes of pneumonia, with or without aetiological confirmation. 8. Invasive cervical cancer.
  • 27. REVISED WORLD HEALTH ORGANIZATION (WHO) CLINICAL STAGING OF HIV/AIDS FOR ADULTS AND ADOLESCENTS (2005) • Primary HIV infection • Asymptomatic • Acute retroviral syndrome • Clinical stage 1 • Asymptomatic • Persistent generalized lymphadenopathy • Clinical stage 2 • Moderate and unexplained weight loss (<10% of presumed or measured body weight) • Recurrent respiratory tract infections (such as sinusitis, bronchitis, otitis media, pharyngitis) • Herpes zoster • Recurrent oral ulcerations • Papular pruritic eruptions • Angular cheilitis • Seborrhoeic dermatitis • Onychomycosis (fungal nail infections)
  • 28. • Clinical stage 3 • Conditions where a presumptive diagnosis can be made on the basis of clinical signs or simple investigations • Unexplained chronic diarrhoea for longer than one month • Unexplained persistent fever (intermittent or constant for longer than one month) • Severe weight loss (>10% of presumed or measured body weight) • Oral candidiasis • Oral hairy leukoplakia • Pulmonary tuberculosis (TB) diagnosed in last two years • Severe presumed bacterial infections (e.g. pneumonia, empyema, meningitis, bacteraemia, pyomyositis, bone or joint infection) • Acute necrotizing ulcerative stomatitis, gingivitis or periodontitis • Conditions where confirmatory diagnostic testing is necessary • Unexplained anaemia (< 80 g/l), and or neutropenia (<500/µl) and or thrombocytopenia (<50 000/ µl) for more than one month
  • 29. • Clinical stage 4 • Conditions where a presumptive diagnosis can be made on the basis of clinical signs or simple investigations • HIV wasting syndrome • Pneumocystis pneumonia • Recurrent severe or radiological bacterial pneumonia • Chronic herpes simplex infection (orolabial, genital or anorectal of more than one month's duration) • Esophageal candidiasis • Extrapulmonary tuberculosis • Kaposi's sarcoma • Central nervous system toxoplasmosis • HIV encephalopathy
  • 30. • Conditions where confirmatory diagnostic testing is necessary • Extrapulmonary cryptococcosis including meningitis • Disseminated non-tuberculous mycobacteria infection • Progressive multifocal leukoencephalopathy • Candida of trachea, bronchi or lungs • Cryptosporidiosis • Isosporiasis • Visceral herpes simplex infection • Cytomegalovirus (CMV) infection (retinitis or of an organ other than liver, spleen or lymph nodes) • Any disseminated mycosis (e.g. histoplasmosis, coccidiomycosis, penicilliosis) • Recurrent non-typhoidal salmonella septicaemia • Lymphoma (cerebral or B cell non-Hodgkin) • Invasive cervical carcinoma • Visceral leishmaniasis
  • 31. CLINICAL MANIFESTATIONS • Clinical features are classified into 4 major categories : • 1) Initial infection with virus and development of antibodies • 2) Asymptomatic carrier stage • 3) AIDS - related complex (ARC) • 4) AIDS
  • 32. 1. Initial infection: Most HIV infected persons have only mild illness (fever, sore- throat and rash) which they experience a few weeks after initial infection. They have these symptoms for first 5 years or so. HIV antibodies take between 2-12 weeks to appear in blood stream. The period before antibodies is "window period". During this period, infected individual will test negative on standard antibody blood test. 2. Asymptomatic carrier stage: Infected people have antibodies, but no overt signs of disease, except generalized lymphadenopathy is present. 3. AIDS related complex (ARC): Here damage to immune system occurs but without opportunistic infections and cancers associated with AIDS. Patients show clinical signs like unexplained diarrheoa lasting longer than a month, malaise, fatigue, loss of more than 10% body weight, fever, night sweats. 4. AIDS: is the end stage of 'HIV infection. A number of opportunistic infections occur. Death is due to uncontrolled infection.
  • 33.
  • 34. MUSCULOSKELETAL MANIFESTATIONS IN HIV INFECTED PATIENTS • Principles to keep in mind when evaluating an HIV infected patient with musculoskeletal syndrome include : 1. Any musculoskeletal syndrome in non-HIV infected patients can occur in HIV infected. 2. HIV infection can alter clinical presentation and course may be more severe in presentation. 3. Early diagnosis of infections is important to prevent spread in an immunocompromised patients.
  • 35.
  • 36. REACTIVE ARTHRITIS • Reactive arthritis: refers to acute non-purulent arthritis complicating an infection elsewhere in the body. • HIV virus associated arthropathy is not associated with extra-articular infections or HLA-B-27. • Outside the setting of HIV infection, reactive arthritis occurs predominantly in individuals who have inherited B27 gene, in most series in which shigella, yersinia or clamydia are the triggering agents.
  • 37. • Clinical features: • Arthritis is usually asymmetric with involvement of new joints occurring over a period of few days to 1-2 weeks. • Reactive arthritis usually occurs in foot and ankle. • The joints of lower extremities especially knee, ankle, and subtalar, metatarsophalangeal and toe interphalangeal joints are the most common sites. • Tendinitis and fascitis produce pain at multiple insertion sites (enthesitis) especially Achilles insertion, plantar fascia and anterior and posterior tibial tendons. • Dactylitis or "sausage digit" a diffuse swelling of solitary finger or toe is a distinctive feature of reactive arthritis. • Cutaneous symptoms include psoriasiform rashes, keratoderma blenorrhagia onychodystr0phy and oral ulcers. • Ocular disease includes conjunctivitis and anterior uveitis.
  • 38. • Laboratory findings : – ESR is elevated and mild anaemia may be present • Treatment : – acute arthritis or tendinitis may benefit from local injection of corticosteroids.Patients may need long-term NSAIDS and analgesic therapy.
  • 39. REITER'S SYNDROME • Reiter’s syndrome is classical triad of arthritis, urethritis and conjunctivitis. • It was the first rheumatic syndrome reported in patients with HIV infection. • Arthritis remains active and may increase in severity as HIV disease progresses. • Between 63 and 75% of HIV patients with reiter's syndrome have HLA-B27 cell surface antigen.
  • 40. • Pathogenesis : • The pathogenesis of HIV related Reiter's disease includes : • Decreased CD4 + lymphocytes – • Increased CD8 + cytotoxic lymphocyte • Induction by infectious agents • Enteric organisms like shigella, flexneri, salmonella, c.jejuni and yersinia enterocolitica etc are the cause of infection in HIV associated Reiter's syndrome.
  • 41. • Clinical features : – the lower extremities are mainly involved – Typical involvement is assymetrical and polyarticular, rarely symmetrical. – One knee joint is almost always affected. – Oligoarthritis of large weight bearing joints (usually ankles or knees) – Enthesopathy may involve achilles tendon, plantar fascia, anterior and posterior tibial tendons and tendons of the feet. – Frank synovitis may occur at ankle and subtalar, metatarsophalangeal and interphalangeal joints of feet. – Multidigit dactylitis, especially in upper extremities. – Synovitis of wrist, elbow and shoulder may lead to contracture and joint fusion but is not common. – Enthesopathy may occur at medial and lateral epicondylar, rotator cuff or flexor tendons of the digits.
  • 42. • Urinary tract involvement: acute non-specific urethritis. • Ocular involvement: Mild conjunctivitis and iritis • Mucocutaneous lesions : superficial ulcerations of mouth occur.Subungual hyperkeratotic lesions elevate and may separate nails. • x-ray findings : • Early, in mild arthritis, slight soft—tissue thickening and minimal subchondral osteoporosis may be seen. • Later, subchondral osteoporosis becomes pronounced and joint space narrows. • Finally, destructive changes may lead to ankylosis. • Peripheral joints: • Destructive changes about the interphalangeal and metatarso phalangeal joints of toes and knee and ankle, subluxation and lateral deviation of toes seen. • Occasionally ankylosis of small joints occurs.
  • 43. • Laboratory findings :  Normal synovial fluid compartment level  Negative tests for rheumatoid factor  Positive HLA-B27 antigen  Positive stool cultures for shigella, yersinia and salmonella • Differential diagnosis :  Reiter's disease is differentiated from rheumatoid arthritis by lack of rheumatoid factor and antinuclear antibody.
  • 44. • Treatment: • NSAID's like indomethacin (50mg 3 times / day provide relief for enthesopathy). • Phenylbutazone (100mg 2 to 3 times / day) is quite useful in HIV associated reiter's syndrome and should be given in early course of disease. • Sufasalazine has been effective as a second line therapy (lg to 3 g/ day). Sulfa allergy is common in HIV infected patients and may limit the use of sulfa drugs. • Methotrexate, other immunosuppressive agents and phototherapy should be used only with ; extreme caution, associated with sudden fulminate immunodeficiency characterized by the appearance of Kaposi's sarcoma and severe and sometimes fatal opportunistic infections in patients who are HIV infected and have Reiter's syndrome. • Intraarticular corticosteroid injections usually provide effective symptomatic control. The benefits of corticosteroid injections can be augmented by immobilizing the affected joint in a splint for 5 to 7 days after the injection • Orthopaedic treatment: • Aims to prevent deformity and preservation of mobility. The patient is placed at bed rest and weight bearing is forbidden. • NSAID's are prescribed and splint applied and removed at intervals for exercises and application of hot packs.
  • 45. PSORIASIS AND PSORIATIC -LIKE ARTHRITIS • The incidence of psoriatic arthritis in HIV infected individual is 2-3%. Patients with HIV infection and psoriatic arthritis fall into one of two patterns of disease. • The articular disease is sustained and aggressive, progressing to joint erosions. • Characterized by mild and intermittent joint involvement. • Clinical manifestations : • Most common sites of involvement are the foot and the ankle. • There is severe enthesopathy and dactylitis, especially in the feet which may lead to deformities. • Frank synovitis and synovial effusions can occur at ankle, subtalar, metatarso— phalangeal and interphalangeal joints of the feet. • The radiological appearance of these joints may mimic classic psoriatic arthritis with "pencil in cup" deformity, osteolysis of phalangeal and metacarpal bone, small joint ankylosis and marginal erosions. • Presence of skin changes is essential for diagnosis of psoriasis. Small patches on extensor surfaces of elbows or knees or scalp may be found. • Nail involvement occurs in distal interphalangeal joints of hands and feet. Nail involvement with pitting, ridging and subangual-hyperkeratosis is necessary for diagnosis.
  • 47. TREATMENT: • NSAID'S such as indomethacin (75 mg to 150mg /day) can be used for joint symptoms. • Retinoic acid derivatives • Psoralen plus ultraviolet light (PUVA) • Low doses of methotrexate (15-75mg/week) has led to rapid (< 4 weeks) improvement in inflammatory joint symptoms as well as improvement in skin lesions. Methotrexate can be given until skin and joint disease is under control, then slowly tapered aiming for a maintenance dose of 5mg/week.Patients must be monitored closely,because there are reports of immunodeficiency and Opportunistic infections in HIV infected individuals who are treated with methotrexate. • Intra-articular steroid injection (every 4-6 months) may provide relief.
  • 48. SEPTIC ARTHRITIS • Septic arthritis is an acute arthritis due to Specific bacteria and productive of purulent exudate. Septic arthritis occurs more commonly in intravenous drug abusers and hemophiliacs who are HIV infected. • Most common pathogens: • Staphyloccus aureus and streptococcus pneumoniae • In advanced HIV infected patients — gonococcus, sporothrix, haemophillus influenzae, salmonella, Candida. • Mode of infection: hematogenous from an infective focus, (soft tissue or bone infection) • Clinical features: Joints affected are knees, shoulder and hip. In drug abusers, S.I joint, symphysis pubis, strenoclavicular and intervertebral discs are also involved. – Usually, one joint is involved which is swollen, red warm and tender. – Pain accentuated by joint movement and increases in intensity over several hours. – Patient limps if lower extremity involved. • Laboratory findings: aspirated joint is serous, serosanguineous or frankly purulent. High leukocytosis and positive C-reactive protein. • Radiographic features reveal osteopenia and joint effusion.
  • 49. • Treatment: – Drainage: in suppurative joint disease immediate and free drainage is mandatory. – Antibiotics: penicillin or a cephalosporin may be combined with an aminoglycoside which is effective against gram positive and gram negative organisms. – Immobilization: limb is immobilized in a removable splint and is elevated. The limb is slowly mobilized in subacute subsiding stage to prevent ankylosing adhesions. – Differential diagnosis: septic arthritis can be difficult to differentiate from reactive arthritis but culture of blood and synovial fluid is sterile in case of reactive arthritis.
  • 50. HIV ASSOCIATED ARTHROPATHY • HIV infected individuals experience a variety of joint problems without obvious caused that are referred to as HIV or AIDS associated arthropathy. • This syndrome is characterized by subacute, oligoarticular arthritis developing over a period of 1 to 6 weeks and lasting 6 weeks to 6 months. • It generally involves the large joints, mainly the knees and ankles and is non-erosive with only mild inflammatory response. • X-ray of joints are non-revealing. • NSAIDS are marginally helpful. Relief has been noted with the use of intraarticular glucocorticoids.
  • 51. PAINFUL ARTICULAR SYNDROME • A second form of arthritis also thought to be secondary to HIV infection. This syndrome occurs due to direct effect of HIV on the joint. • This condition is found in 10% of AIDS patients. It affects primarily knees, shoulders and elbows and lasts for 2 to 24 hours. Presents as acute severe sharp pain in affected joints. • Narcotic analgesics help in severe cases.
  • 52. OSTEOMYELITIS • The commonest cause of radiologically demonstrable bone lesions is infection . A large number of reports exist describing osteo- myelitis affecting unusual sites and involving unusual organisms. • The commonest sites are spine and long bones,followed by chest wall and clavicles . • Normally pathogenic bacteria, Staphylococcus aureus and Salmonella spp., are the most frequently encountered. • Others such as Cryptococcus neoformans, MTB, Histoplasma capsulatum, Nocardia asteroides and Mycobacterium avium complex (MAC) have been described. • Involvement of the spine, sacrum or sacroiliac joints should suggest MTB infection . Involvement with Actinomyces sp., or less commonly Candida albicans, causes rib destruction and a chest wall mass.
  • 53. •The radiographic findings are as for osteomyelitis in the general population. –MRI shows a focus of fluid within the bone marrow, perhaps breaching the cortex, and usually extensive bone marrow oedema often affecting the entire length of the bone. Periostitis is typical on all modalities. –CT is useful for demonstrating the densely calcified sequestrum. •Treatment is with appropriate antibiotics and occasionally surgical debridement. Response to treatment is poorer in immuno- compromised patients.
  • 54. MYOSITIS •Infectious myositis, also called pyomyositis or tropical myositis, was a rare diagnosis in temperate climates prior to the HIV era. Infectious myositis presents subacutely over two to three weeks; three phases have been described. •The initial invasive phase is marked by local tenderness and mild swelling of the involved muscle, and occasionally with low-grade fevers. After one to three weeks, a purulent phase develops, with painful induration, edema, local rise of temperature without erythema, and systemic fevers. •Most patients present during this phase and may have leukocytosis and an elevated sedimentation rate, but CK levels are usually surprisingly low. Blood cultures are rarely positive at this stage.
  • 55. •MRI is the most sensitive diagnostic tool, but ultrasound and CT scanning will also reveal a purulent abscess in the involved muscle; occasionally more than one muscle is involved. •Left untreated, a third disseminated phase ensues, with septic shock and associated morbidity. •S.aureus, streptococcus pyogens, Cryptococcus neoformans, M.tuberculosis are the organisms responsible.
  • 56. Clinical features : • In first stage, Patients present with pain localized to one muscle group and with low grade fever. Here aspiration does not reveal pus. • In second (suppurative stage), pain, fever and oedema of affected muscle present. Here aspiration reveals pus. • Third stage, is diagnosed when patient appears septic. A fluctuant abscess is noted and entire muscle may be necrotic. • Treatment : Small abscess can be cured by systemic antibiotics but multiple or large abscesses need surgical incision and drainage.
  • 57. IDIOPATHIC POLYMYOSITIS • Polymyositis is the term applied to a group of idiopathic disorders characterized pathologically by degenerative and inflammatory changes of skeletal muscle and clinically by severe muscle weakness chiefly affecting proximal muscle groups about the pelvic and shoulder girdles, the anterior neck muscles and often muscles of deglutition. • Progressive proximal weakness of lower and upper extremities (less common) is the most frequent complaint. • Distal weakness is mild and rare. • Muscle pain, bilateral and symmetrical, involving shoulder and upper arm is present in most patients. • Dysphagia is a prominent feature at the onset in one fourth of patients. • Upper limb contractures occur in 10% of patients and involve elbows and fingers. • There is increasing difficulty in rising from a chair, walking up stairs and using arms for any length of time.
  • 58. • The dose of prednisolone is gradually tapered when the serum enzymes return to normal. • Maintenance dose of 5mg-15mg/day is reached depending on clinical response. This dose is required to prevent further worsening of muscle weakness and elevation of muscle enzymes. • Immunosuppressive agents: – steroid resistant cases are tried with immunosuppressive agents like methotrexate and azathioprine. • Orthopaedic treatment: – during early stage, warm, moist pack applied. – Gentle passive range of motion exercises. – Splints to prevent deformities
  • 59. SOME OTHER MUSCULOSKELETAL MANIFESTATIONS OF HIV • Bursitis: – Septic bursitis is a well described entity in immunocompromised patients. – S. aureus is the most common etiologic agent. – Infection localizes to olecrenon, prepatellar and less frequently, subdeltoid bursae. • Kaposis sarcoma : – Is a multifocal spindle cell neoplasm. – Most common neoplasm in HIV infected patients. – Patients present with bone pain. – X-ray reveals cortical erosion, osseous destruction and periosteal reaction. • Avascular necrosis: – HIV induced vasculitis has been postulated as a cause. – Affects any joint, mainly hip. – Joint pain is the complaint – X-ray shows patchy sclerosis, collapse and secondary degenerative disease. • Fibromyalgia: – Occurs in I.V drug users who are HIV positive – It is characterized by widespread musculoskeletal pain, stiffness, paresthesia, disturbed sleep, easy fatigability, dizziness, depression and loss of short-term memory. – Multiple, painful tender points which are symmetrically distributed. – NSAIDs and antidepressants help.
  • 60. MANIFESTATIONS OF DRUG TOXICITY A. AZT associated myositis a) Drug allergies are the most significant allergic reactions occurring in HIV—infected patients and appear to become more common as the disease progresses.Idiosyncratic reactions to AZT include muscular weakness and elevated CPK levels. Patients showing muscular symptoms have a subacute onset of myalgia, proximal weakness and muscle tenderness.Muscle biopsy shows myofibril necrosis and associated inflammation.Electromyograms show myopathic changes. b) Treatment : prednisolone (lmg/kg/day for 10-14 days) can be given for muscle pain, weakness and elevated CPK levels. As CPK levels normalize and symptoms resolve,prednisolone can be tapered off gradually. c) Another antiretroviral agent can be used if clinically indicated. d) If CPK levels are mildly elevated, but there are no clinical symptoms, patient can choose to continue with AZT therapy or to switch to another antertroviral agent. B. Drug allergies, also occur with TMP/SMX. A. TMP/SMX are used for treatment of PCP.These reactions are characterized by erythematous, morbilliform eruption that are pruritic, and often associated with fever. C. With abacavir (nucleoside analogue) hypersensitivity reaction has been noted.
  • 61. RISKS AND PREVENTION • Emanuel described three factors that must be known to calculate the orthopaedic surgeon's risk of occurring HIV from punctures in operating room: - – Frequency of punctures – Percentage of surgical patients who are HIV positive – Risk of HIV transmission per needlestick from known HIV-positive Patients. • Risk increases with increased viral load of patient, quantity of blood injected and depth of inoculation. • The risk of transmission per needle stick is around 0.3% as estimated by CDC. • Annual risk to the orthopaedic surgeon is between 0.025% 0.5% according to CDC.
  • 62. • Prevention : • The surgeon should know the causes, associated diseases affecting musculosketal system, risks of transmission and precautions to be taken. • The guidelines for surgery should include assessment of HIV— positive patient's immune status, including CD4 lymphocyte count, history of opportunistic infection, and state of nutrition and general health. • In the absence of an effective means of prophylaxis, chief defence, against HIV infection is prevention of transmission. • Lacerations from bone fragments and edges, as well as cuts and needle sticks must be avoided.
  • 63. AAOS RECOMMENDATIONS FOR OPERATING ROOM PROCEDURES 1. Avoid use of sharp instruments if possible. 2. Avoid direct passing of sharp instruments between team members. 3. Use notouch technique 4. Use a scalpel for skin incisions only, then scissors and electrocautery 5. Avoid simultaneous suture of same layer by two members of a team 6. Prefer to use blunt suture needles 7. Avoid hasty gestures 8. Comply with regulations for elimination of disposable material 9. Always wear gloves when handling material covered with blood.
  • 64. UNIVERSAL PRECAUTIONS • The initial CDC recommendations called for blood and body fluid precautions when a patient was known or suspected to be infected with blood borne pathogens. The CDC called for precautions to be consistently used all the time regardless of apparent blood borne infection status of a given patient. These universal precautions are intended to prevent parenteral, mucous membrane, and nonintact skin exposures of health care workers to blood- bome pathogens. – During a surgical operation, when an overt sharp injury occurs, the aseptic barrier is broken, injured worker leaves the operating field and returns on the reestablishment of asepsis. • With double gloving, such gross contamination is reduced. Double gloving technique reduces risk of blood contact from 29% to 18% however gloves must be changed every 2 hours or every hour for trauma cases. – Greater than half of needle-stick injuries occurred to index finger of non—dominant hand. There should be additional re-inforcement to this portion of glove on routine use. – Glasses/transparent shields should be worn to prevent contact of blood to eyes during operations. – Sharp objects should be passed in trays to avoid accidental pricks .Due to high prevalence of HBV infection in HIV infected individuals, all health care workers and surgeons dealing with HIV infected patients should be immunized with HBV vaccine. • The success of universal precautions is limited. Gloves do not prevent needle-stick or other penetrating sharp injuries, and gloves certainly can tear. Latex gloves appear preferable to vinyl as rates of perforation in latex gloves is much lower than polyvinyl chloride gloves.
  • 66. CAUSES OF FALSE-POSITIVE AND FALSE-NEGATIVE REACTIONS IN ENZYME IMMUNOSAYS FOR ANTIBODY TO HIV • Antibodies against HLA • Passive immunization with HIV antibody-positive immunoglobulin • Alcoholic liver disease • Lymphoma . • Influenza immunization • Acute viral infection • Chronic renal disease Stevens-Johnson syndrome • Conditions that have been associated with false-negative tests • Acute HIV infection-seroconversion usually occurs within 3-6 months; antibody testing may be negative during this window period • lmmunosuppressive therapy • Immune deficiency (B—cell defects) • Rheumatoid factor • Late-stage AIDS • Exchange transfusion • Different assay systems
  • 67. CONTROL OF AIDS • 1) Prevention – a) Education : People should be educated on AIDS, its nature, transmission and prevention. – b) Prevention of blood-borne transmission. • All blood should be screened for HIV-1 and HIV-2 before transmission. Strict sterilizing practices should be ensured in hospitals and clinics. • 2) Antiretroviral treatment: Antiviral chemotherapy has proved to be useful in prolonging life of ill patients. • 3) Specific prophylaxis : Here manifestations of AIDS are treated. – Primary prophylaxis against P carinii -pneumonia with CD4 count below 200 cells/(j.L ‘ • Trimethoprim-sulfamethoxazole, lDS/day pentamidine (300mg /month) and dapsone (100mg/day) ' • M. Avium complex - Rifabutin (300mg/day) • Prophylaxis against M. tuberculosis • INH 300 mg daily for 9 months to 1 years + pyridoxine 25-50mg/day • 4) Primary health care - AIDS touches all aspects of primary health care including mother and child health, family planning and education.
  • 68. POST-EXPOSURE PROPHYLACTIC TREATMENT • After the exposure of health care workers to HIV infected blood, chemoprophylaxis is offered. • This treatment is started within 2 hours of exposure and generally recommended for at least a 4 week course. • The following treatment is recommended by the US centre for disease control and prevention: • a) Double combination of treatment with – - AZT (200 mg 3 times daily + Lamivudine (3TC) (150 mg twice daily) for 4 weeks • b) If “source” individual has advanced A1 3. – Protease inhibitor (nelflnavir) (750 mg 3 times daily) should be added to the AZT/3TC regimen' • e) If “source” individual has failed on AZT/3TC therapy Stavudine (d4t) plus ddl should be used
  • 69. CONCLUSION • Epidemiologic and laboratory observations suggest that HIV infection is transmitted through intimate sexual contact or through parenteral contact with blood or blood products. It also appears likely that this retrovirus produces a spectrum of disease ranging from subclinical to fatal. A better understanding of epidemiology of AIDS will aid in designing better prevention strategies. Health care workers and others should familiarize themselves with, and follow, the recommended precautions when handling specimens, secretions and excretions of persons known to be infected with the virus.
  • 70. REFERENCES : • Harisson's principles of internal medicine - 17th edition. • PSM textbook - Park • Robbin's pathologic basis of disease – 8thedition • Orthopaedics principles and their application - Turek, 4th edition • Campbell's operative orthopaedics - 11th edition • Mercer's Orthopaedic surgery • Radiologic clinics of North America Medical clinical of North America.