HOUSE M.D. DECODED

The FIVE O Tuberous sclerosis O Kawasaki’s Disease O Histiocytosis O Erdheim-Chester Disease O Lymphoma

Tuberous sclerosis

Genetics O Mutations in two tumour-suppressor genes O TSC1, TSC2 O Autosomal dominant disease O Affects nervous system

Signs & Symptoms O Hamartomas O Benign, focal malformation O Grows at same rate as surrounding tissues O Growing in a disorganised mass

Signs & Symptoms O Cortical hamartomas (in brain): O Benign tumours O Firm O Likened to potatoes – hence “tubers” O Haphazardly arranged neurons O Mixed expression of glial and neuronal features

Signs & Symptoms - SKIN O Cutaneous lesions O Angiofibromas (reddish growths on skin with fibrous tissue) O Shagreen patches: leathery thickenings in localised patches O Ash-leaf patches: hypopigmented areas O Subungual fibromas (rough growths under fingernails/toenails)

Signs & Symptoms - BRAIN O Developmental delays O Mental retardation O Seizures that are difficult to control with antiepileptic drugs

Signs & Symptoms - OTHERS O Renal angiomyolipomas O Hematuria O Retinal glial hamartomas O Pulmonary lesions O Cardiac rhabdomyomas (benign tumour of striated muscle) O Cysts at liver, kidneys, pancreas

Histiocytosis O Describes a rare group of diseases O Characterised by abnormally high number of histiocytes (macrophages and dendritic cells) O The Histiocytes (e.g. macrophages/dendritic cells) act like cancer cells and may attack skin, bones, muscles and other important organs

Histiocytosis Langerhans Cell Histiocytosis (e.g.Hand-Schuller-Christian Disease) Excessive proliferation of specifically Langerhans cells (type of dendritic cell) Non-Langerhans Cell Histiocytosis (e.g.Erdheim-Chester Disease) Excessive proliferation of tissue macrophages (type of cell surface glycoproteins are also different) Malignant Histiocytic disorders

Dendritic cell

Macrophage

Erdheim-Chester Disease O Cause is unknown and is a relatively rare disease O Usually affects adults: mean age is 53

Symptoms O Bone pain O Retroperitoneal fibrosis O Diabetes insipidus O Exophthalmos O Xanthomas O Neurological signs (including Ataxia) O Dyspnea caused by interlobular septal and pleural thickening O Kidney failure O Hypopituitarism O Liver failure

Symptoms O Bone: The most-frequently seen symptom is painful bone swelling. The skull is most frequently affected. Osteolytic lesions can lead to pathological fractures. O Skin: Commonly seen are a rash which varies from scaly erythematous lesions to red papules O Lymph node: Enlargement of the liver in 20%, spleen in 30% and lymph nodes in 50% of histiocytosis cases O Lungs: some patients are asymptomatic, diagnosed incidentally because of lung nodules on radiographs; others suffer from chronic cough and shortness of breath

Diagnosis O Histology O Radiology osteosclerosis (increased bone density: due to damaged bone tissue) (for EDC) O Bone Lesions (for LCH)

Treatment O Chemotheraphy O E.g.Cladribine: Chemically, it mimics the neucleoside adenosine inhibiting enzyme adenosine deaminase interfering with DNA processing (but easily destroyed by normal cells)

Kawasaki Disease O Etiology unknown O Higher incidence in those of Japanese descent O Autoimmune disease: inflammation of medium-sized blood vessels throughout body O Affects both arteries and veins

Symptoms O Onset: High and persistent (at least 5 days) fever of 38°C or higher O Bloodshot eyes O Bright red, chapped, or cracked lips O Red mucous membranes in the mouth O Strawberry tongue, white coating on the tongue, or prominent red bumps on the back of the tongue O Red palms of the hands and the soles of the feet O Swollen hands and feet (edema) O Skin rashes on the middle of the body O Peeling skin in the genital area, hands, and feet O Swollen lymph nodes (neck) O Joint pain and swelling, frequently on both sides of the body

Diagnosis O No specific test exists for KS O Diagnosis is clinical, based on observation of symptoms: 1) 5 days of fever 2) Erythema (redness) of lips 3) Rash on trunk 4) Edema / erythema of hands and feet 5) Red eyes 6) Swollen lymph nodes, at least 1.5 cm

Possible complications O Cardiac complications O Danger: Coronary artery aneurysm due to blood vessel damage in ~25% of untreated children  myocardial infarction  death O Inflammation of mitral/tricuspid valves  lesions and dysfunction O Aneurysm of other arteries O Intestinal obstruction O CNS damage – meningoencephalitis, cerebral infarction

Treatment O Intravenous gamma-globulin O May greatly increase immunoglobulin- destroying mechanisms by overloading body systems O High doses of aspirin O Anti-inflammatory agent, binds to and inhibits multiple enzymes involved in inflammation

Lymphomas

What Cancer of the lymphocytes (NK, T, B cells) WherePresents as proliferation of lymphocytes in lymph nodes Can also be extranodular Cf. lymphoid leukaemias (not static tumours, but circulating) S&S Anorexia Dyspnea Fatigue Fever of unknown origin Lymphadenopathy Night sweats Itching Weight loss

Lymphatic system Transport of fluid, fatty acids, white blood cells incl. antigen- presenting cells

Lymph nodes Filters / traps foreign particles

Implications of Lymphoma Physical: Pressure on surrounding tissue (the usual problem of all tumours) Physio: Weakened immune system

Reed–Sternberg cells (also known as lacunar histiocytes for certain types) are different giant cells found with light microscopy in biopsies from individuals with Hodgkin's lymphoma (aka Hodgkin's disease; a type of lymphoma) primarily due to EBV, and certain other disorders. They are usually derived from B lymphocytes. Reed–Sternberg cells

Treatment Chemotherapy + methotrexate