HOUSE M.D.DECODED

The FIVEO Tuberous sclerosisO Kawasaki’s Disease O Histiocytosis O Erdheim-Chester DiseaseO Lymphoma

Tuberous sclerosis

GeneticsO Mutations in two tumour-suppressor

genesO TSC1, TSC2

O Autosomal dominant diseaseO Affects nervous system

Signs & SymptomsO Hamartomas

O Benign, focal malformationO Grows at same rate as surrounding

tissuesO Growing in a disorganised mass

Signs & SymptomsO Cortical hamartomas (in brain):

O Benign tumoursO FirmO Likened to potatoes – hence “tubers”O Haphazardly arranged neuronsO Mixed expression of glial and neuronal

features

Signs & Symptoms - SKIN

O Cutaneous lesionsO Angiofibromas (reddish growths on

skin with fibrous tissue)O Shagreen patches: leathery

thickenings in localised patchesO Ash-leaf patches: hypopigmented

areasO Subungual fibromas (rough growths

under fingernails/toenails)

Signs & Symptoms - BRAIN

O Developmental delaysO Mental retardationO Seizures that are difficult to control

with antiepileptic drugs

Signs & Symptoms - OTHERS

O Renal angiomyolipomasO Hematuria

O Retinal glial hamartomasO Pulmonary lesionsO Cardiac rhabdomyomas (benign

tumour of striated muscle)O Cysts at liver, kidneys, pancreas

HistiocytosisO 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

SymptomsO Bone painO Retroperitoneal fibrosisO Diabetes insipidusO ExophthalmosO XanthomasO Neurological signs (including Ataxia)O Dyspnea caused by interlobular septal and

pleural thickeningO Kidney failureO HypopituitarismO Liver failure

SymptomsO 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

DiagnosisO HistologyO 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 DiseaseO Etiology unknownO Higher incidence in those of

Japanese descentO Autoimmune disease: inflammation

of medium-sized blood vessels throughout bodyO Affects both arteries and veins

SymptomsO Onset: High and persistent (at least 5 days) fever of 38°C or

higherO Bloodshot eyes O Bright red, chapped, or cracked lipsO Red mucous membranes in the mouthO Strawberry tongue, white coating on the tongue, or

prominent red bumps on the back of the tongueO Red palms of the hands and the soles of the feetO Swollen hands and feet (edema)O Skin rashes on the middle of the bodyO Peeling skin in the genital area, hands, and feetO Swollen lymph nodes (neck)O Joint pain and swelling, frequently on both sides of the body

DiagnosisO No specific test exists for KSO Diagnosis is clinical, based on

observation of symptoms:1) 5 days of fever2) Erythema (redness) of lips3) Rash on trunk4) Edema / erythema of hands and feet5) Red eyes6) Swollen lymph nodes, at least 1.5 cm

Possible complicationsO 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 arteriesO Intestinal obstructionO CNS damage – meningoencephalitis,

cerebral infarction

TreatmentO Intravenous gamma-globulin

O May greatly increase immunoglobulin-destroying mechanisms by overloading body systems

O High doses of aspirinO Anti-inflammatory agent, binds to and

inhibits multiple enzymes involved in inflammation

Lymphomas

WhatCancer of the lymphocytes (NK, T, B cells)

Where Presents as proliferation of lymphocytes in lymph nodesCan also be extranodularCf. lymphoid leukaemias (not static tumours, but circulating)

S&S Anorexia Dyspnea Fatigue Fever of unknown origin Lymphadenopathy Night sweats Itching Weight loss

Lymphatic systemTransport of fluid, fatty acids, white blood cells incl.

antigen-presenting cells

Lymph nodesFilters / traps foreign particles

Implications of LymphomaPhysical: 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

TreatmentChemotherapy + methotrexate