Overview
Scleroderma (and its subtype systemic sclerosis) is a disease of:
Fibrosis
- Fibrosis, which refers to a thickening and ultimate tightening and stiffening of the skin and/or the internal organs.
- Fibrosis occurs via collagen and extracellular matrix protein deposition.
- Specifically, there is direct activation of fibroblasts (which produce collagen) and immune-cell mediation fibroblast activation; fibrosis-inducing antibody production; and transition of cutaneous and subcutaneous cells into collagen-producing myofibroblasts.
Microvasculopathy
- Obliterative microvasculopathy.
Inflammation
- A strong inflammatory response accompanies these pathologies.
Autoantibodies
- The following are helpful diagnostic autoantibodies for scleroderma – if we think “genetics” we can more easily remember these auto-antibodies because they are involved in genetics in some way:
Centromere
- Anti-centromere antibody (the centromere attaches DNA strands)
Topoisomerase I
- Anti-topoisomerase I (aka scl-70) antibody (topoisomerase cuts & pastes DNA strands)
RNA polymerase III
- Anti-RNA polymerase III antibody (RNA polymerase III is involved in gene transcription)
Nomenclature
Localized scleroderma
- Localized scleroderma if there is only skin involvement (no internal organ pathology).
Systemic sclerosis
- Systemic sclerosis if there is multisystem organ involvement (skin and internal organ involvement).
- Especially, gastroesophageal reflux disease (GERD), we can imagine how GI fibrosis could lead to reflux.
- And, interstitial lung disease, which can lead to pulmonary hypertension (as we saw in sarcoidosis) – again we can imagine how lung parenchyma fibrosis would lead to restricted lung compliance and resultant pulmonary hypertension.
Additional Nomenclature
We can then further subdivide cases of systemic sclerosis into:
- Limited scleroderma (skin involvement is limited to distal extremities and face).
- Diffuse scleroderma (skin involvement can affect the entire body).
- It’s easy to misconstrue that the “limited” vs “diffuse” designation somehow reflects the degree of internal organ involvement, which it does not; these terms only reflects the pattern of skin involvement. For example, limited scleroderma can have severe organ involvement but the skin involvement, itself, is restricted to the distal extremities and face.
- Scleroderma sine scleroderma. Finally, you may run across the term scleroderma sine scleroderma, which is an extremely rare form of scleroderma without any skin involvement (only internal organ involvement).
Clinical Manifestations
- Now, let’s address some key clinical manifestations. Starting with the outward, visible symptoms and signs:
Sclerodactyly
- Sclerodactyly is a key sign of fibrosis: tightening and hardening of the skin, which leads to clawing and curling of the hand and a glistening appearance to the skin.
- Fibrosis actually begins with puffing-up of the skin before it tightens down.
Calcinosis
- Calcinosis refers to subcutaneous calcium deposits that can rupture through the skin – the thick, white deposits can be visualized.
- They can accumulate along the limbs and cluster at the joint spaces, causing severe inflammatory arthropathy.
Ulceration
- Ulceration occurs from obliterative microvasculopathy.
Nailfold Microvasculopathy
- Nailfold microvasculopathy also occurs from obliterative microvasculopathy.
- For reference, the nailfold lies proximal to the cuticle, which lies proximal to the lunula the half-moon (crescent-shaped) white area at the base of the fingernail.
- We show a row of normal appearance nailfold capillaries.
- We show giant capillaries and hemorrhages, which are an early sign of active disease, and small, atrophic capillaries, which we see in later stage scleroderma.
- Abnormal nailfold capillaries can be visualized with the naked eye but various tools allow us to magnify the nailfold and more thoroughly visualize and distinguish the pathologic causes of the nailfold capillary pathology – various connective tissue disorders cause a variety of pathologies.
- Importantly, nailfold capillary examination can help distinguish primary Raynaud’s phenomenon (no additional disease) from Raynaud’s that is secondary to a connective tissue disorder: the nailfold capillaries are normal in primary Raynaud’s but can be abnormal in Raynaud’s that is secondary to connective tissue disease.
Raynaud’s phenomenon
- Raynaud’s phenomenon, which as discussed elsewhere, can potentially be a key sign of scleroderma but needs to be distinguished from idiopathic Raynaud’s or Raynaud’s secondary to another connective tissue disease.
Telangiectasias
- Similar to nailfold capillary vasculopathy, we show facial telangiectasias – spidery capillary dilations.
Mouth: Lip thinning/Oral aperture reduction/Fissuring
- And we show that the mouth can be tightened down as well, in addition to the hands and other body regions, with thinning of the lips and narrowing (reduction) of the oral aperture (the opening of the mouth). We show that the skin around the mouth can be fissured from this tightening.