Granulomatous Diseases Flashcards
Liver TRMs
Kupffer cells
Spleen and secondary lymphoid organ TRMs
Sinus histiocytes
CNS TRMs
Microglia
Lung TRMs
Alveolar macrophages
Five main functions of macrophages
- Phagocytosis
- Fibrosis
- Antigen presentation
- Tissue destruction/remodeling
- Angiogenesis
Th1-derived ___ activates ___ to secrete ___ which is repsonsible for inducing and maintaining granuolmas.
Th1-derived IFN-g activates macrophages to secrete TNF-a which is repsonsible for inducing and maintaining granuolmas.
“Naked granuloma”
No or minimal lymphocytes surrounding granuloma
Granulomas
- Assembly of macrophages in tissue, which may appear as “epithelioid histiocytes”
- May or may not contain giant cells
- May or may have lymphocytic involvement
Blood cell lineage diagram
Monocytes circulate for ___ before entering the tissue where they live for ___ as histiocytes
Monocytes circulate for only a few hours to days before entering the tissue where they live for months to years as histiocytes
Histiocyte
A term for monocytes that have entered a tissue
Bone TRMs
Osteoclasts
Kidney TRMs
Intraglomerular mesangial cells
While ___ have a phenotype similar to that of a dendritic cell, they are in fact derived from ___.
While Langerhans cells have a phenotype similar to that of a dendritic cell, they are in fact derived from blood monocytes.
Monocyte-derived lineages
Dendritic cells AND macrophages
Foreign body granuloma
Foreign body granuloma
Clinically, foreign body granulomas may appear as . . .
. . . erythematous papules, plaques or dermal or subcutaneous nodules. They can sometimes become scaly, weepy, or ulcerate.
Fish Tank Granuloma
- Caused by Mycobacterium marinum
- Usually seen in individuals who clean aquariums or sell fish and have a small cut or are exposed to contaminated water
- Often the lesion heals fine, but then ~3 weeks later a verrucous or wart-like papule or nodule will emerge at the site of injury, then begins to spread
- Lesions may be asymptomatic or may be painful if tissue containing nerves is involved
- Progression typically very slow, over the course of years
- Treatment involves months of antibiotics
Verrucous cutaneous tuberculosis
Tuberculosis marinum infection spreads in the body via the ___.
Tuberculosis marinum infection spreads in the body via the lymphatics.
Multiple erythematous nodules spreading linearly via the lymphatics. Initial spread of M. marinum
Chronic granulomatous disease
- Characterized by recurrent, life-threatening bacterial and fungal infections and granuloma formation
- Caused by genetic deficiency in Phox
Massive lymphadenopathy in CGD
Massive lymphadenopathy of CGD
Symptoms and signs of pulmonary sarcoidosis
- Dyspnea
- Dry cough
- Normal physical exam, possibly crackles on lung auscultation
- Chest X-ray reveals hilar and mediastinal lymphadenopathy
Symptoms and signs of cutaneous sarcoidosis
- Systemic involvement
- Sometimes referred to the “great immitator” for its difficulty to pin down
- Violaceous papules (eyelids & nostrils)
- When nostril rim involved, respiratory track involved
- Violaceous plaques & nodules (face, neck, & extremities)
Cutaneous sarcoidosis of the eye
What do the arrows show?
Beading in cutaneous sarcoidosis
Sarcoidosis in knee scar
Diascopy
- Press glass slide against a lesion
- Reveals characteristic apple jelly color in granulomatous inflammation
Joint involvement in sarcoidosis
- May appear as acute polyarthritis involving periarthritic symptoms and with symmetric involvement, often of ankles
- In chronic cases, periosteal bone resorption creates cysts which may be detected on X-ray
- May cause substantial deviation at DIPs
Eye involvement in sarcoidosis
- 25% of patients
- Presents as uveitis with substantial redness and vasodilation
- Highly correlated with systemic involvement
- Can involve many parts of the eye (orbit, lacrimal glands, muscle, conjunctiva, sclerae)
Differential for sarcoidosis
Major differentials are infection and cancer
Treatment of sarcoidosis
- Oral steroids
- Other immunosuppressants
Clinical variants of Sarcoidosis
- Löfgren’s Syndrome: More mild form. Tetrad of hilar lymphadenopathy, acute periarthritis of ankles, fever and/or uveitis, erythema nodosum
- Lupus Pernio: Severe form of sarcoidosis. Lymphadenopathy, organomegaly, uveitis, bone cysts. Very difficult to treat.
Erythema nodosum
- Hypersensitivity reaction which may result from drugs, infections, or induction of autoimmune disease
- Development of multiple erythematous patches
Cutaneous sarcoidosis (lupus pernio)
Cutaneous sarcoidosis
Lupus pernio variant
Cutaneous sarcoidosis, subcutaneous variant
Lupus pernio
Crohn’s disease
- IBD characterized by granulomatous inflammation along the entire GI tract
- Can also manifest in the skin, joints, eyes and kidneys
- Mucosal T cells secrete large amounts of TNF-a and IFN-g which produces ongoing acute and chronic inflammation of GI tract
- abdominal pain, bloody diarrhea, peritoneal signs
- Increases risk of gut colonization by microbes
Normal IG vs Crohn’s GI vs UC GI
Extracutaneous manifestations of Crohn’s
Eosinophilic Granulomatosis with Polyangiitis
- Granulomatous vasculitis of small- and medium-sized vessels of unclear etiology
- chronic allergic rhinitis, sinusitis, asthma, peripheral eosinophilia, and lung and skin disease
- vasculitic lung disease can cause lung nodules and alveolar hemorrhage
- Cutaneous vasculitis can cause subcutaneous nodules or palpable purpura
- Granulomatous nodules can be seen on the elbows and knees
Suppurative granuloma
- Granuloma with a central abscess
- Defined by epithelioid histiocytes and multinucleate giant cells with a central collection of neutrophils
- May occur with necrotizing or non-necrotizing granulomatous inflammation
- Associated with coccidiomycosis and Bartonella henselae (cat scratch disease)
Naked granulomas are associated with. . .
. . . sarcoidosis
When you diagnose a patient with sarcoidosis, always immediately order ___.
When you diagnose a patient with sarcoidosis, always immediately order an EKG.
If a sarcoidosis patient is found to have heart involvement, what steps should be taken?
Implantation of a pacemaker and debibrillator.
In a non-naked granuloma, the T cells will be . . .
. . . intermixed with the macrophages, not just surrounding it. Even if there are a ton of T cells surrounding the granuloma, it is a naked granuloma.
The apple jelly sign for granulomas is. . .
. . . very specific, but not very sensitive
Findings: Reynaud’s and telangiectasias of the finger nail beds and palm.
What is your likely diagnosis?
Scleroderma
Findings: Raynaud’s, malar rash, and alopecia
What is the likely diagnosis?
Lupus
Findings: Raynaud’s, palpable purpura, and fingertip necrosis
What is your likely diagnosis?
Medium vessel vasculitis
Findings: Raynaud’s, Gottron’s papules, and GERD
What is the likely diagnosis?
Dermatomyositis
Gastric antral vascular ectasia
aka GAVE aka watermelon stomach
Associated with anti-RNA Pol III
