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So it’s not just about HIV?….. Professor Steve Green Sheffield Copyright Green 2013 • Some slides and photos have been removed from this presentation due to its size • If this is a problem to you, please contact [email protected] I am NOT an immunologist Copyright Green 2013 You never know what new diseases are in the pipeline….. Copyright Green 2013 “There’s something wrong with my immune system, doctor” Copyright Green 2013 We are what we eat •“Summer” •Giuseppe Arcimboldo (1527 – 1593) Copyright Green 2013 Some people have some interesting ideas about food… Copyright Green 2013 Even eating people…. • Francisco Goya (1746 – 1828) • “Saturn Devouring One of His Children” • 1820-22 Copyright Green 2013 It seems to have caught on… • “Dracula” (1958 • “Sean of the Dead” (2004) Copyright Green 2013 Copyright Green 2013 Food is in the eye of the beholder Copyright Green 2013 Some do it quite graphically Copyright Green 2013 What has nature done to protect us? Copyright Green 2013 Copyright Green 2013 Complement Copyright Green 2013 More that can go wrong….. Toll-like receptors Copyright Green 2013 And even more that can go wrong… Copyright Green 2013 Let’s just look at it through the clinician’s eyes!...... Copyright Green 2013 It isn’t just about HIV…. • Other infections that can modify the immune system • Congenital problems • Medications • Malignancies • Toxins • Radiation • Others Copyright Green 2013 External agents Copyright Green 2013 External agents • Medications – Immunological therapies – Corticosteroids – Drugs for the transplant scenario – Drugs for cancer • Other things Copyright Green 2013 Medications utilising immune suppression Amazingly useful for –Autoimmune conditions –Asthma –Cancer –Transplant medicine But –All immunosuppressive drugs have the potential to cause immunodeficiency –Immunodeficiency may manifest as increased susceptibility to opportunistic infections and decreased cancer immunosurveillance Copyright Green 2013 Something different…. Copyright Green 2013 Adult T-cell leukaemia/lymphoma • • • • • • • • • • Lady aged 52 From Jamaica Lymphadenopathy Fever Anorexia Fatigue Night sweats Pruritis Blood film and bone marrow examination T-cell leukaemia/lymphoma Copyright Green 2013 Adult T-cell leukaemia/lymphoma • Tested for HTLV-1 • Positive Copyright Green 2013 Next steps • Huge extended family • Incidentally a number of the family members have sickle cell trait too Copyright Green 2013 Copyright Green 2013 Acute meningococcal infection • • • • • • • • Man in his 50s Went on the Haj Vaccinated with Meningococcal ACWY vaccine Came back Febrile, widespread rash, low BP Resuscitated Improved Blood cultures grew N. meningitidis W-135 Copyright Green 2013 • Monoclone identified • Positive Bence-Jones proteins • Multiple myeloma Copyright Green 2013 Male GP in his 60s • Diabetic • Chronic renal failure • Went to India…… Copyright Green 2013 Male GP in his 60s • • • • Diabetic Chronic renal failure Went to India Came back with a new kidney • On immunosuppressive drugs • Then…… Copyright Green 2013 Acute hepatitis B • Unable to stop immunosuppressive drugs or rejection would supervene • Terrible liver problems • Eventually started on lamivudine • Died Copyright Green 2013 Copyright Green 2013 Medical advancement abounds… Copyright Green 2013 Biologicals • Rheumatology – Rheumatoid Disease • Dermatology – Psoriasis • Gastrenterology – Crohn’s disease • Etc etc etc Copyright Green 2013 But….. • There are many potential infectious complications of biological therapy • Bacterial infections, such as tuberculosis, Streptococcus pneumoniae and Listeria monocytogenes • Potential reactivation of viral infections such as hepatitis B or C, herpes simplex and herpes varicella zoster • Pre-treatment screening vital • Vaccination where appropriate • Post-treatment surveillance vital Copyright Green 2013 Copyright Green 2013 The shoe fitting flouroscope Copyright Green 2013 Copyright Green 2013 Intrinsic things Copyright Green 2013 Sudden death • • • • • Man in his 40’s Develops a “chest infection” Collapses Unable to resuscitate Very severe DIC-syndrome Copyright Green 2013 Copyright Green 2013 • He had been treated surgically after a road traffic accident • A splenectomy had been undertaken • He was not otherwise immunodeficient • He had never received any specific follow-up or vaccinations Copyright Green 2013 Causes of hyposplenism • • • • • Trauma Congenital hyposplenism Coeliac disease Removal for staging of lymphoma etc Splenic infarction – e.g. sickle cell disease Copyright Green 2013 Prone to • • • • • Meningococcaemia Haemophilus influenzae Capnocytophagia canimorsus Plasmodium falciparum malaria Babesiosis Copyright Green 2013 What may you see? • Howell Jolly bodies • Target cells • Ultrasound/CT may show no spleen Copyright Green 2013 What can be done? • Splenectomy card • Vaccinations – Meningococcus ACWY – Polyvalent pneumococcus – Haemophilus influenzae B – Annual influenza • ? Prophylactic antibiotics Copyright Green 2013 Herpes zoster • Cancer. – Cancer places people at risk for herpes zoster. – At highest risk are those with Hodgkin's disease • 13 - 15% of these patients develop shingles – About 7 - 9% of patients with lymphomas, and 1 - 3% of patients with other cancers, develop herpes zoster. – Chemotherapy itself increases the risk for herpes zoster • Immunosuppressant Drugs. – Patients who take certain medications that suppress the immune system are at risk for herpes zoster (as well as other infections) e.g. • • • • • • • Azathioprine Chlorambucil Cyclophosphamide Cyclosporine Cladribine Infliximab Adalimumab Copyright Green 2013 How far do you investigate?... Copyright Green 2013 Bat wing shadows on CXR Copyright Green 2013 Pneumocystis jiroveci on BAL Copyright Green 2013 Associations • Patients taking corticosteroids or other immunosuppressants • Patients with haematological malignancy • Organ transplant recipients • Congenital immune deficiency, eg thymic aplasia, severe combined immune deficiency (SCID), hypogammaglobulinaemia • Severe malnutrition – poor nutrition in HIV-positive individuals increases risk Copyright Green 2013 Common things are common Copyright Green 2013 Diabetes mellitus • Look out for – – – – – – Candidiasis Tuberculosis Pyelonephritis Malignant otitis externa Mucor mycosis Listeria monocytogones Copyright Green 2013 Our genetic hand Copyright Green 2013 Copyright Green 2013 David Vetter David Vetter (1971 - 1984 Copyright Green 2013 Copyright Green 2013 Congenital immune deficiency Copyright Green 2013 Sore fingernails Copyright Green 2013 Chronic mucocutaneous candidiasis • Usually begins during infancy but sometimes during early adulthood. • Candidal infections develop and become persistent • The disorder may affect just one nail or cause a disfiguring rash that covers the face and scalp. The rash is crusted and thick and may ooze. On the scalp, the rash may cause hair to fall out. • Leading to – oral thrush – membranes lining the mouth, eyelids, digestive tract and vagina – infections of the scalp, skin, and nails • in infants, the first symptoms are often thrush that is difficult to treat, persistent nappy rash, or both, and severity varies • It may also be associated with a wide range of endocrine disorders….. Copyright Green 2013 Copyright Green 2013 Epidermodysplasia verruciformis • Autosomal recessive • Abnormal immune response to HPV Copyright Green 2013 Terminal complement deficiency • Terminal complement pathway deficiency is a genetic condition affecting the complement membrane attack complex (MAC). Copyright Green 2013 • One sees deficiencies of C5, C6, C7, and C8 – NB. while C9 is part of the MAC, and deficiencies have been identified, it is not required for cell lysis • People with this condition are prone to meningococcal infection. • Vaccination is recommended • Don’t forget influenza! Copyright Green 2013 Duncan's Syndrome • X-Linked Lymphoproliferative Disease • Inability to mount an immune response to EBV • Leads to bone marrow failure, irreversible hepatitis, and malignant lymphoma • Death Copyright Green 2013 Plus • Non-deliberate immunosuppression can occur in Copyright Green 2013 But if you have a good immune system…. Copyright Green 2013 “There’s something wrong with my immune system, doctor” Copyright Green 2013 If you don’t, help is at hand…… Copyright Green 2013 Thank you Copyright Green 2013