Scleroderma & Sjögren’s

[Scleroderma] "The disease is characterized by 3 main hallmarks—vascular insult, autoimmunity, and tissue fibrosis." NIAMS: "researchers think that the immune system overreacts and causes inflammation and injury to the cells that line blood vessels." "This triggers connective tissue cells, especially a cell type called fibroblasts, to make too much collagen and other proteins." "Too much collagen in your skin and other tissues causes areas of tight, hard skin." Injured endothelium releases endothelin-1, "a potent vasoconstrictor," and "The initial vascular insult ultimately results in tissue hypoxia."

[Scleroderma] Localized versus systemic. Localized scleroderma (morphea) "only affects the skin and the structures directly under the skin" and "is not associated with increased mortality." Systemic sclerosis "is the more serious type of scleroderma and can damage your blood vessels and internal organs, such as the heart, lungs, and kidneys." It is "limited systemic sclerosis (formerly known as CREST syndrome, characterized by calcinosis, Raynaud phenomenon, esophageal dysmotility, sclerodactyly, and telangiectasia) or diffuse systemic sclerosis." Limited disease affects skin "distal to the elbows and knees, with the trunk typically spared"; diffuse disease "involves skin proximal to the elbows, knees, and/or the trunk" and "typically presents more severe symptoms and higher mortality rates."

[Scleroderma] Not inherited. NIAMS: "You cannot inherit the disease, and it is not passed from parent to child like some genetic diseases." "However, first-degree relatives of people with scleroderma are at higher risk." Silica dust and some solvents are associated; "cigarette smoking is not a proven risk factor" for getting it — though smoking still worsens vessels and lungs.

[Raynaud’s] "Raynaud phenomenon is characterized as a transient, peripheral vasoconstrictive response to cold temperatures or emotional stress." Color change runs "initial pallor with well-defined white discoloration, followed by ischemic changes with a dusky bluish appearance, and finally, reactive hyperemia leading to red discoloration" — though "not all patients report all 3 color phases." NHS: it "may make your fingertips appear paler if you have brown or black skin." Primary Raynaud’s "is not associated with underlying systemic illness and is characterized by reversible vasospasm without tissue injury"; secondary Raynaud’s "is usually associated with an underlying disease, most commonly a connective tissue disease (CTD), such as scleroderma, systemic lupus erythematosus, Sjögren syndrome, or antiphospholipid syndrome." In scleroderma it appears "in over 95% of patients," and structural vessel disease makes it severe: "digital ulceration of the tips of the fingers and toes may develop because of prolonged vasoconstriction and subsequent tissue ischemia."

[Scleroderma] Renal crisis. "Decreased blood flow from the structural changes in the blood vessels as well as renal vasospasm (“Raynaud’s phenomenon”) causes renal ischemia, hyperplasia of the juxtaglomerular apparatus, activation of the renin-angiotensin-aldosterone system (RAAS), and rise in BP." "The critical rise in BP causes further damage to renal blood vessels and initiates a vicious cycle eventually leading to malignant hypertension." It "presents with the abrupt onset of severe hypertension accompanied by rapidly progressive renal failure, hypertensive encephalopathy, congestive heart failure, and/or microangiopathic hemolytic anemia." It mainly affects diffuse disease, usually early — StatPearls (SSc): "Scleroderma renal crisis occurs in approximately 10% of systemic sclerosis patients" and "typically manifests within three years of diagnosis"; StatPearls (renal crisis): "up to 75% of cases" within the first 4 years. It can occur without hypertension — StatPearls lists "Scleroderma renal crisis occurring without hypertension" among poor-outcome features.

Why an ACE inhibitor. Because renin drives the cycle, "ACE inhibitors represent the sole effective treatment for scleroderma renal crisis." Steroids can precipitate it: "High-dose corticosteroids and long-term use of low to moderate-dose corticosteroids have been associated with the precipitation of scleroderma renal crisis."

[Sjögren’s] NIAMS: "Sjögren’s disease, also known as Sjögren’s and Sjögren’s syndrome, is a chronic (long-lasting) autoimmune disorder that happens when the immune system attacks the glands that make moisture in the eyes, mouth, and other parts of the body." "The characteristic lesion of Sjögren disease, focal lymphocytic sialadenitis (FLS), affects exocrine glands." "This dysfunction reduces tear and saliva production by the lacrimal and salivary glands, respectively." Other glands dry the skin, airways and vagina.

[Sjögren’s] Who and with what. "symptoms most commonly begin between the ages of 45 and 55," with "a female-to-male ratio of approximately 9:1." It "frequently occurs in conjunction with other autoimmune disorders including rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE)" — "secondary Sjogren or Sjogren-overlap disease" — and scleroderma raises the risk of "secondary Sjögren syndrome." "Up to one-half of affected individuals also develop extra-glandular involvement" — joints, skin, lungs, gut, nerves and kidneys.

[Sjögren’s] Lymphoma — relative versus absolute risk. B cells "capable of transforming into malignant clones" raise the risk of MALT lymphoma. StatPearls cites "an 8.7-fold increased risk"; NIAMS adds that "the risk of developing it is low," and NHS describes non-Hodgkin lymphoma as rare. Red flags include "persistent salivary gland swelling, enlarging lymph nodes, leukopenia, palpable purpura, and low complement C4."