Systemic Connective Tissue Diseases

Skin examination: dermatological signs

The skin and mucous membranes are often the first to signal the development of autoimmune pathology. Characteristic visual signs allow the physician to narrow down the diagnostic search:

• Systemic lupus erythematosus (SLE): a classic manifestation is erythema located on the bridge of the nose and cheeks, visually resembling a "butterfly" silhouette.
• Dermatomyositis: accompanied by vivid facial erythema combined with marked periorbital edema. In clinical practice, this specific sign is termed the "spectacles" sign.
• Hemorrhagic syndrome: manifests on the skin as petechiae and ecchymoses, indicating involvement of the vascular bed.
• Other erythemas: annular, erythema multiforme, and erythema nodosum forms are encountered. Erythema nodosum has historically had a close association with rheumatism.

Extrahepatic manifestations: a diagnostic trap

Chronic liver diseases, such as active hepatitis or cirrhosis, present a particular diagnostic challenge. They often proceed covertly, and their systemic manifestations completely mimic SLE, scleroderma, or rheumatoid arthritis. Liver disease may manifest exclusively with the following syndromes:

1. Articular syndrome: persistent arthralgia or the development of full-blown arthritis.
2. Fever: has a non-infectious genesis. It is extremely important to differentiate it from infectious hectic fever (accompanied by chills and profuse sweating), which is characteristic of cholangitis, liver abscess, or cholecystitis.
3. Vascular disorders: development of Raynaud's syndrome, clinically known as the "dead fingers" phenomenon.
4. Sicca syndrome (Sjögren's syndrome): includes impaired saliva production (xerostomia), tear deficiency (keratoconjunctivitis sicca), and, as a direct consequence, rapidly progressive multiple caries.

Precise verification of primary liver damage requires a thorough history taking and targeted biopsy.

Systemic disorders in multiple myeloma

Systemic lesions are also characteristic of oncohematological processes. The pathogenesis of myeloma is based on tumor infiltration of internal organs by plasma cells (their pool in the bone marrow exceeds 15%).

• Kidney involvement and calcium metabolism: the tumor actively mobilizes calcium from bone tissue. This leads to hypercalcemia and subsequent nephrocalcinosis. Myeloma nephropathy develops with proteinuria and cylindruria (hematuria is usually absent). A specific marker is the detection of a homogeneous band (M-spike, paraprotein) upon urine electrophoresis.
• Amyloidosis and blood viscosity: amyloid formation leads to its deposition in the dermis, joints (causing arthralgia), and muscles (provoking macroglossia and cardiac involvement). Due to marked hyperproteinemia, a hyperviscosity syndrome arises, impairing microcirculation and producing neurological symptoms (headaches).
• Diagnostics: blood tests reveal anemia, leukopenia, and often (though not in 100% of patients) a significantly accelerated ESR. The serum protein electrophoresis demonstrates an "M-component"—a narrow paraprotein band, most frequently in the $\gamma$-globulin zone. Diagnostic imaging (CT, X-ray) shows typical "punched-out" foci of osteodestruction.
• Treatment: is based on radiation therapy and cytotoxic agents (alkylating agents such as melphalan and cyclophosphamide, as well as nitrosourea derivatives).

Important clarification: monoclonal gammopathies are not 100% specific to myeloma alone; they can be detected in liver cirrhosis and systemic connective tissue diseases.

Rheumatic fever (Rheumatism)

This is a systemic inflammatory disease of autoimmune origin in which the heart and joints become the main targets. The disease runs a relapsing course, referred to as "rheumatic attacks".

Etiology and pathogenesis: Rheumatism develops as a complication following infection with group A $\beta$-hemolytic streptococcus (GAS). The key mechanism of damage is the phenomenon of "molecular mimicry". Streptococcal antigens structurally resemble normal human tissues (specifically, the myocardial sarcolemma). As a result, antibodies produced by the immune system against the bacterium cross-attack the body's own heart tissues. Polygenic inheritance plays an important role, determining individual immune reactivity.

Clinical presentation: Disease onset most commonly occurs in childhood and adolescence (under 15 years of age) and manifests 2–3 (sometimes up to 4) weeks after a previous streptococcal sore throat. The typical triad of onset includes:

1. Signs of carditis.
2. Polyarthritis.
3. Elevated body temperature.

The insidiousness of rheumatic fever lies in the fact that in more than 1/3 of patients, the acute phase proceeds latently, due to which the diagnosis is often established only at the stage of an established heart valve defect.

Class and exam questions

What else to study on this topic

• Diagnostic criteria and laboratory markers of systemic lupus erythematosus
• Mechanisms of secondary amyloidosis formation in paraproteinemias
• Differential diagnosis of monoclonal gammopathies of undetermined significance
• Principles of secondary antibiotic prophylaxis for rheumatic attacks

Other topics in the "Additional Topics" section

Prepared by WhiteCoat Pro faculty in accordance with the medical school curriculum. For educational purposes only.