Sarcoidosis
Overview
- Sarcoidosis is a heterogenous multisystem chronic inflammatory disease granulomatous disease with pulmonary involvement in > 90% of cases.
- It is about two to three times more common in blacks than in whites and slightly more common in women than in men.
Histopathology: Noncaseating Granulomas
Noncaseating Granulomas
- Sarcoidosis is characterized by its key histopathological finding of noncaseating granulomas.
- Show that they are nodular (ball-like) collections of chronic inflammatory macrophages that have an epithelial appearance, hence their name “epithelioid cells”, surrounded by lymphocytes.
- Use a higher magnification representation to show the that epithelioid cells have large, elongated nuclei and they have pink-stained cytoplasm on H&E staining.
- Their borders are ill-defined because they are so tightly packaged.
- Note that granulomas are NOT exclusively filled with epithelioid cells, other inflammatory and collagenous cells will be spotted within them, as well.
Langhans-type multinucleated giant cells (MNGCs)
- Next, using even higher magnification show that these cells can fuse to form Langhans-type multinucleated giant cells (MNGCs) with a peripherally-arranged horseshoe (aka arcuate) pattern of nuclei.
- From a nomenclature standpoint, note that Langhans-type cells are not the only form of multinucleated giant cell and also pay attention not to confuse these with Langerhan’s cells: epidermal macrophages.
- Also show that the epitheloid nuclei are described as elliptical (think of the Earth’s orbit around the sun to imagine this shape). They can have the appearance of the sole of a slipper, as shown here.
- Importantly, as we see in these depictions, the center of the granuloma is NON-necrotic. This distinguishes the inflammatory granulomas of sarcoidosis from their caseating granuloma counterpart, which have a necrotic, cheese-like appearing center.
Caseating granulomas
- Caseating granulomas are found in infectious diseases, namely tuberculosis (Mycobacterium tuberculosis and M. bovis) but others as well.
- Infectious causes of granulomas (other than tuberculosis) include:
- Inflammatory causes of granulomas (other than sarcoidosis) include:
Key Pulmonary Signs
Bilateral Hilar Adenopathy
- Show bilateral hilar adenopathy, which refers to bilateral lymph node enlargement at the root of the lungs (the hila).
Fibrocystic Changes/Pulmonary HTN
- Next, write out that there can be fibrocystic changes, which can result in pulmonary hypertension.
Hallmark Clinical Manifestations
- It’s helpful to lump other hallmark manifestations in two different constellations of symptoms that can occur – we shouldn’t worry ourselves with the eponyms themselves but use these syndromes to remember common sarcoidosis symptoms.
Löfgren Syndrome
Polyarthritis
- Polyarthritis: a key in an acute flare of sarcoidosis, but in chronic disease, arthralgias (painful joints) without radiographic changes are more common.
Erythema nodosum
- Erythema nodosum: a common skin manifestation.
- As its name suggest, it refers to erythematous (hot, red, painful) nodules (lumps) within the subcutaneous fat layer (panniculitis).
- Show that they typically arise on the tibial surface (the anterior surface) of the lower leg.
Anterior uveitis
- Anterior uveitis: inflammation in the anterior chamber of the eye – the most common ocular manifestation.
Bilateral hilar adenopathy
- Bilateral hilar adenopathy, as previously addressed. Note that lymphadenopathy can occur in other mediastinal and peripheral lymph nodes as well.
Heerfordt Syndrome (Uveoparotid Fever)
Now, let’s use Heerfordt syndrome (aka Heerfordt-Waldenström syndrome or uveopartoid fever – which tells us a lot about the syndrome).
Parotid disease
- As its name suggests, indicate that it manifests with parotid disease. Sarcoidosis can cause painless enlargement/swelling of the parotid, lacrimal, or salivary glands and/or sicca syndrome – dryness of the mouth and eyes, which we’ll address as cornerstone of Sjögren syndrome.
Facial nerve palsy (bilateral)
- Next, indicate facial nerve palsy. Sarcoidosis can affect the nervous system in many ways, which we lump as neurosarcoidosis, but sarcoidosis is one of the few illnesses that can manifest with bilateral Bell’s palsy, so it’s an important potential indicator of this disease.
- Other common neurosarcoidosis manifestations include:
Anterior uveitis
- Now, as we included in Löfgren syndrome, indicate anterior uveitis.
Fever
- Also include low-grade fever, remember the alternate name for this acute presentation is uveopartoid fever. Although chronic sarcoidosis doesn’t cause fever, per say, it is an inflammatory disease and thus fever is a helpful reminder of this pathology.
Additional Clinical Manifestations
Sarcoidosis has numerous other potential manifestations, which include:
- Cutaneous manifestations, namely, plaques and subcutaneous nodules.
- Hepatitis in isolation or as a constellation of “abdominal sarcoidosis”: granulomatous inflammation of the liver, spleen, bone marrow, with hypercalcemia.
- Hypercalcemia due to renal involvement
- Depression
- Cardiac disease, including electrophysiological disease (eg, arrhythmia and heart block) and structural disease (eg, dilated cardiomyopathy).
- Asymptomatic muscle involvement (although inflammatory myopathy can also occur) including infiltration of skeletal and cardiac muscle.