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Rheumatic Diseases

Morbi rheumatici

For medical students2 min readUpdated 2026-10-10

A group of heterogeneous conditions characterized by systemic involvement of connective tissue, along with vascular, cartilaginous, osseous, and muscular tissue damage. The unifying principle of these pathologies is the progressive destruction of the internal organ stroma and musculoskeletal elements driven by profound immune dysregulation.

Core ProcessSystemic progressive disorganization of connective tissue

PathogenesisClosely linked to hypersensitivity reactions (Type I/III and Type IV)

Primary TargetMicrovasculature (development of generalized vasculitis)

Biopsy SitesSkin, kidneys, muscles, and synovial membranes are most commonly examined

General Features and Pathogenesis

According to the International Classification of Diseases (ICD-10), rheumatic diseases comprise over 120 distinct nosologies. Despite this diversity, they share several fundamental features:

Presence of a chronic infectious focus in the body.
Marked alterations in immune homeostasis. Type I/III hypersensitivity (immediate hypersensitivity) and Type IV (delayed-type hypersensitivity) play key roles in pathogenesis.
Systemic nature of connective tissue involvement.
Development of generalized vasculitis.
Chronic, relapsing course characterized by alternating periods of remission and exacerbation.

Morphology: Phases of Disorganization

The morphological hallmark of rheumatic diseases is systemic and progressive connective tissue disorganization. This process follows a strict sequence of 4 distinct phases:

Mucoid swelling.
Fibrinoid changes.
Inflammatory cellular reactions. Inflammation acts as a response to tissue injury, presenting as either exudative or proliferative (productive). The nature of the inflammatory response depends on the specific pathogenesis, anatomical location, and disease stage.
Sclerosis. The final phase of disorganization, where damaged structures are permanently replaced by dense fibrous tissue.

Immunopathology and Vascular Involvement

A key immunopathological driver in rheumatic diseases is damage to the microvasculature, with systemic involvement of arterioles, capillaries, and venules.

Due to the chronic relapsing course, these conditions exhibit marked tissue polymorphism. This means that even within a small biopsy sample, a morphological patchwork is visible: all phases of the process appear simultaneously. Adjacent areas may show fresh connective tissue disorganization, zones of active exudative or proliferative inflammation, and older areas of sclerosis and hyalinosis.

Classification and Diagnostic Principles

Common rheumatic diseases include acute rheumatic fever, rheumatoid arthritis, ankylosing spondylitis (Bechterew disease), and Sjögren syndrome. Note that the term "diffuse connective tissue diseases" (DCTD) specifically refers to five major conditions: rheumatoid arthritis, systemic lupus erythematosus (SLE), systemic sclerosis, polyarteritis nodosa, and dermatomyositis.

Diagnostic Principles:

Multi-organ involvement: Although systemic, the clinical and morphological presentation depends on which organ is primarily targeted.
Biopsy: Theoretically, tissue can be sampled from any site since the entire connective tissue system is affected. In clinical practice, however, diagnostic biopsies most frequently target the skin, kidneys, upper respiratory tract mucosa, synovial membranes, and skeletal muscles.

Mnemonic

To remember the 4 stages of connective tissue disorganization, use the mnemonic My Fibrous Vessels Scar (Mucoid swelling, Fibrinoid changes, Vascular/inflammatory reactions, Sclerosis).

Frequently asked questions

What morphological changes characterize the mucoid swelling stage in rheumatic diseases?

Mucoid swelling is characterized by the accumulation of acidic glycosaminoglycans and plasma proteins, leading to hydration and swelling of the extracellular matrix ground substance.

The morphological picture includes:

Ground substance — swells and increases in volume, pushing connective tissue cells apart.
Collagen fibers — retain their bundle architecture, but swell, undergo fibrillolysis (loose fibril packing), and lose resistance to collagenase.
Cellular reaction — lymphocytes, plasma cells, and macrophages appear.

Staining with hematoxylin and eosin reveals basophilia, while toluidine blue produces metachromasia (areas shift to lilac or red). Macroscopically, organ appearance is minimally altered.

How do fibrinoid changes differ from mucoid swelling during connective tissue disorganization?

Fibrinoid changes represent a profound and irreversible stage of connective tissue disorganization, unlike superficial and reversible mucoid swelling.

Feature	Mucoid Swelling	Fibrinoid Changes
Reversibility	Reversible phase	Irreversible destruction
Glycosaminoglycans	Accumulation and/or redistribution of acidic GAGs	Depolymerization and near-total destruction of GAGs
Ground substance and fibers	Hydration and swelling of ground substance and fibers	Destruction of ground substance and fibers
Collagen fibers	Retain bundle structure, swell and loosen	Homogeneous, eosinophilic; evidence of fiber rupture
Metachromasia	Present with toluidine blue stain	Absent
Fibrinoid	Not described as a characteristic feature	Fibrinoid formation occurs; fibrin is an obligatory component

During fibrinoid swelling, vascular permeability increases sharply, blood plasma proteins infiltrate the connective tissue, and fibrinoid is formed. Fibrinoid swelling often culminates in fibrinoid necrosis.

What specific granulomas form in acute rheumatic fever (Aschoff-Talalaev disease)?

Acute rheumatic fever features specific Aschoff-Talalaev granulomas (rheumatic granulomas), which form predominantly in the perivascular stroma of the heart in response to fibrinoid necrosis.

The cellular composition of the granuloma includes:

Anitschkow cells — large epithelioid cells with basophilic cytoplasm. Their nuclei have a characteristic appearance: an "owl-eye" look in cross-section or a "caterpillar" look in longitudinal section. They are pathognomonic for rheumatic carditis.
Aschoff cells — multinucleated giant histiocytes.

Granuloma evolution progresses through three stages: "flower-like" (maximal cellular activity and macrophage accumulation), "fading" (reduction in cellularity as Type I/III immunity shifts to Type IV), and "scarring" (resulting in focal sclerosis).

What changes occur in immune system organs (lymph nodes, spleen) during rheumatic diseases?

Immune system organs display distinct alterations associated with the immunopathological process.

Confirmed morphological changes include:

Lymphoid tissue — hyperplasia with plasmacytic transformation.
In rheumatoid arthritis — lymph node and splenic hyperplasia with plasmacytic transformation, alongside bone marrow plasmacytosis.
In systemic lupus erythematosus — the spleen exhibits "onion-skin" periarterial fibrosis, follicular hyperplasia, and plasmacytic pulp infiltration.

These changes are evaluated within the context of chronic immunoinflammatory processes characteristic of rheumatic diseases.

Why can different stages of tissue damage be found in a single biopsy specimen?

This is due to the chronic relapsing (wave-like) course of the disease. New flares overlap with older lesions, resulting in the simultaneous presence of fresh disorganization, active inflammation, and areas of sclerosis with hyalinosis within the tissue.

What is the difference between rheumatic diseases and diffuse connective tissue diseases (DCTDs)?

Rheumatic diseases comprise a broad group of over 120 disorders. The term "diffuse connective tissue diseases" (DCTDs) is specifically reserved for five of them: rheumatoid arthritis, SLE, systemic sclerosis, polyarteritis nodosa, and dermatomyositis.

Where are biopsies taken from to confirm the diagnosis?

Because the disease is systemic, theoretically any body site is suitable. In practice, clinicians most frequently sample the skin, kidneys, upper respiratory mucosa, synovial membranes, and skeletal muscles.

What is the unifying principle for all diseases in this group?

The primary unifying principle is the involvement of connective tissue, which forms the stroma of internal organs and the structural framework of the musculoskeletal system.

Go deeper

Pathogenesis and morphology of acute rheumatic fever
Pathological anatomy of rheumatoid arthritis and ankylosing spondylitis
Renal involvement in systemic lupus erythematosus (SLE)
Skin and internal organ changes in systemic sclerosis
Morphology of vasculitis in polyarteritis nodosa