Systemic findings in rheumatic diseases
Prof Dr. Aşkın Ateş
İç Hastalıkları ABD/Romatoloji BD
Constitutional symptoms
• Constitutional symptoms such as fever, weakness and weight loss are common in rheumatic diseases.
• The most common rheumatic diseases with persistent fever are
Adult onset Still Disease
Vasculitis (especially polyarteritis nodosa, temporal arteritis, ANCA- associated vasculitis)
Systemic lupus erythematosus
Rheumatic fever
Familial mediterranean fever (the most common periodic fever syndrome)
Other periodic fever syndromes : Hyperimmunoglobulinemia; Tumor necrosis factor (TNF) receptor– associated periodic syndrome; Muckle- Wells syndrome (MWS) Familial cold autoinflammatory syndrome
(FCAS)
İnflammatory myositis rarely (especially antisynthetase syndrome)
• Skin is involved frequently in rheumatic diseases.
• Skin manifestations can be hallmark features in some
rheumatic diseases, especially lupus erythematosus,
dermatomyositis, and systemic sclerosis.
Systemic lupus erythematosus
• Systemic lupus erythematosus (SLE) is a chronic multisystem disease
characterized by diffuse vasculitis and inflammation of connective tissues that may lead to widespread organ damage affecting the kidneys, brain, and joints.
• SLE is an autoimmune condition marked by abnormalities of B and T lymphocytes and the complement system. The hallmark of the disease is the production of autoantibodies against nuclear and cytoplasmic antigens that cause tissue damage through the deposition of
antigen-antibody complexes, complement activation, and direct antibody- and cell-mediated cytotoxicity.
• Current pathogenic models indicate that the disease evolves through the complex interplay of immune, genetic, infectious, hormonal, and environmental factors.
• Skin involvement is the second most common manifestation of SLE after arthralgias and arthritis.
• Arthritis and arthralgias have been noted in up to 95 percent of patients with systemic lupus erythematosus .
• The arthritis and arthralgias of SLE tend to be migratory;
symptoms in a particular joint may be gone within 24 hours.
Involvement is usually symmetrical and polyarticular with a
predilection for the knees, carpal joints, and joints of the
fingers, especially the proximal interphalangeal (PIP) joint.
• The key dermatologic signs of SLE are malar rash, discoid lesions, oral ulcers, and nonscarring alopecia.
• Three forms of cutaneous lupus erythematosus (CLE), localized or generalized, involving the epidermis, dermis, or subcutaneous fat of the skin can be part of the clinical presentation of SLE.
Acute lesions (Acute cutaneous lupus erythematosus) (ACLE)
Subacute lesions (SCLE)
Chronic lesions (CCLE)
Acute cutaneous lupus erythematosus
• The hallmark skin lesion of ACLE in patients with SLE is malar rash, which is a reddish maculopapular eruption in a
characteristic butterfly distribution (“butterfly rash”) on the face.
• In most cases patients recall induction or exacerbation of the rash by exposure to ultraviolet (UV) light, thus indicating that photosensitivity is an important diagnostic clue and
pathogenetic component. Lesions tend to be transient, last
from several hours to weeks, and heal without scarring.
Subacute cutaneous lupus erythematosus
• Two variants of SCLE have been identified: an annular (or arcuate) variant consisting of slightly raised erythema with central clearing and a
papulosquamous variant consisting of psoriasis-like or eczematous-like lesions, both typically located on UV-exposed skin, including the lateral aspects of the face, the V of the neck (often with sparing of the area under the chin), the upper ventral and dorsal part of the trunk , and the
dorsolateral aspects of the forearms.
• SCLE lesions never lead to scarring, but hypopigmentation or
depigmentation as a result of postinflammatory destruction of epidermal melanocytes is a common complication during the healing process of these skin lesions , especially in patients with darker skin phenotypes.
Chronic cutaneous lupus erythematosus
• The prototypic skin lesion of the classic form of CCLE, also
known as discoid CLE, is an erythematous discoid plaque that becomes hyperkeratotic and eventually leads to atrophy and scarring.
• Dyspigmentation, including hypopigmentation and hyperpigmentation, is common. Discoid lesions have a predilection for the face, ears, and neck but may be
widespread without a clear-cut relationship to UV exposure.
Idiopathic inflammatory myopathies (IIMs)
• Idiopathic inflammatory myopathies (IIMs) are a group of autoimmune diseases targeting skeletal muscles as well as skin, joints, and other organ systems. The IIMs have traditionally been divided into polymyositis (PM), dermatomyositis (DM), and inclusion body myositis (IBM). More recently, immune-mediated necrotizing myopathy (IMNM) has been recognized as a unique autoimmune myopathy.
• Painless symmetric proximal muscle weakness with or without rash typically is present.
• Serum muscle enzymes (at least two serum muscle enzyme activities from the following: Creatine kinase, aldolase, LDH, ALT, and AST) are increased in most patients, most notably creatine kinase
• Electromyographic abnormalities reflect proximal myopathy and muscle
membrane instability, and muscle biopsy demonstrates inflammatory infiltrates.
DERMATOMYOSITIS
• Dermatomyositis is the one of the inflammatory myopathies characterized by inflammatory and degenerative changes of the muscles and skin.
• Affected individuals may experience difficulty in performing certain functions, such as raising their arms and/or climbing stairs or
develop speech and swallowing difficulties.
• Key dermatologic signs of DM include heliotrope rash, Gottron
papules, Gottron sign, periungual telangiectases, and calcinosis
cutis.
Gottron sign. Scaling and macular erythema are evident over the extensor surface of the elbow in a patient with dermatomyositis.
Gottron papules. This erythematous, scaling rash over the knuckles and dorsum of the hand is a common early sign of DM.
“Shawl” sign in a patient with dermatomyositis
featuring an erythematous rash across the upper part of the back and
extending onto the neck in the
distribution of where a shawl is worn.
V-neck rash in a patient with dermatomyositis
demonstrating its photosensitive nature over
the anterior aspect of the chest.
Facial rash of dermatomyositis. Note the malar- like
rash of dermatomyositis, which also involves the nasolabial fold (an area often spared in systemic lupus erythematosus). Patchy involvement of the forehead and chin is also present.
Heliotrope rash of dermatomyositis demonstrating
both erythema and diffuse periorbital edema
Systemic sclerosis
• Systemic sclerosis (SSc), also called scleroderma, is an immune-
mediated rheumatic disease that is characterised by fibrosis of the skin and internal organs and vasculopathy.
• The term sclerosis describes hardening or induration as a result of excessive deposition of interstitial collagen and subsequent tissue fibrosis.
• Key dermatologic signs of SSc include Raynaud phenomenon,
symmetric cutaneous sclerosis, finger swelling, sclerodactyly, digital
pits and ulcers, dilated or atrophic nail-fold capillaries, calcinosis
cutis, and hyperpigmentation.
Classification of Systemic sclerosis (SSc)
SSc is classified as
• Limited SSc (CREST syndrome)
• Generalized SSc (with diffuse skin involvement)
• SSc sine scleroderma
• In limited SSc (CREST syndrome—calcinosis cutis, raynaud phenomenon, esophageal dysmotility, sclerodactyly, telangiectasias), patients develop skin tightening over the face and distal to the elbows and knees and may also have gastroesophageal reflux disease. This type is characterized by slow progression and is often complicated by pulmonary hypertension.
• In generalized SSc with diffuse skin involvement, patients have Raynaud phenomenon and gastrointestinal complications. This type typically evolves rapidly. Interstitial lung disease and scleroderma renal crisis are the major complications.
• In SSc sine scleroderma, patients have SSc-related antibodies and visceral manifestations of the disease but no skin tightening.
The telangiectasias seen in patients with SSc are often located on the face, including the lips, but may also be detected on the neck, volar aspects of the fingers, and palms
Digital pitting scars
Loss of substance of the digital finger pads (pulp loss) Digital ulcers
• Calcinosis is another key feature of CREST syndrome and tends to be located on the extremities, especially at the fingertips and over joints .
• A relatively unappreciated skin sign in patients with SSc is skin hyperpigmentation. It occurs mostly as a diffuse brownish
discoloration resembling a suntan and is usually accentuated in areas of friction and pressure. Variants of skin discoloration in patients with diffuse SSc do occur and include “salt and
pepper,” which describes a combination of hyperpigmentation
and hypopigmentation often found on the upper part of the
trunk.
Diffuse hyperpigmentation of the skin in a patient with systemic sclerosis. Note also the
depigmentation in the submammary region
Calcinosis Cutis
Digital pits on the fingertip of a patient with scleroderma.
Calsinosis cutis
Contractural changes affecting the digits with foci of calcification and isolated telangiectasia
Raynaud Phenomenon
• Raynaud phenomenon is the overarching term to describe transient, reversible blanching of the digits caused by vasospasm and ischemia in response to cold or emotional stimuli.
• Skin discoloration occurs because an abnormal spasm of the blood vessels causes a diminished blood flow to the local tissues. Initially, the digit(s) involved turn white because of the diminished blood flow.
• The digit(s) then turn blue (cyanosis) because of prolonged lack of oxygen.
Finally, the blood vessels reopen, causing a local "flushing" phenomenon, which turns the digit(s) red.
• This three-phase color sequence (white to blue to red), most often upon exposure to cold temperature, is characteristic of RP
• Primary Raynaud‘s phenomenon, this most common form isn't the result of an associated medical condition. It can be so mild that many people with primary Raynaud's don't seek treatment. And it can resolve on its own.
• Secondary Raynaud's phenomenon, this form is caused by an underlying problem. Although secondary Raynaud's phenomenon is less common than the primary form, it tends to be more serious.
Systemic sclerosis (90%)
Mixed connective tissue disease (85%)
Sjögren syndrome (33%)
Systemic lupus erythematosus (10%–45%)
Polymyositis or dermatomyositis (20%)
Rheumatoid arthritis (10%–15%)
The hands of a patient with scleroderma who has active Raynaud phenomenon. There is well-
demarcated pallor of the fingertips
blue (cyanosis)
blue (cyanosis)
Adult-onset Still's disease
• Adult-onset Still's disease (AOSD) is a systemic inflammatory disorder of unknown etiology usually affecting young adults.
• AOSD typically manifests with a symptomatic triad
characterised by spiking fever, arthritis and maculo-papular salmon-pink evanescent skin rash.
• A large percentage of AOSD patients may show an evanescent salmon-pink erythema which may be associated with an
erythematous maculopapular eruption, predominantly found
on the proximal limbs and trunk, appearing during the febrile
attacks. Some patients, with usually more severe outcome,
may experience this eruption for many weeks.
The color of the lesions is pink to red, and
koebnerization is common Erythematous maculopapular eruption, predominantly found on the proximal limbs and trunk
Vasculitis
• Vasculitis can affect the small- or medium-sized vessels of the skin. Vasculitis affecting the small vessels of the skin (eg,
arterioles, capillaries, postcapillary venules) tends to cause lesions such as palpable purpura, petechiae, and possibly shallow ulcers.
• Livedo reticularis, nodules, and deep ulcers are usually caused by vasculitis of deeper, medium or large vessels.
• Any primary (ANCA-associated vasculitis, Polyarteritis nodosa, Cryoglobulinaemic vasculitis, Henoch-Schölein purpura) or
secondary vasculitis can affect the skin, including that due to
infections (eg, hepatitis C), malignancy, rheumatologic (SLE,
RA, Sjögren syndrome)or other autoimmune disorders, and
hypersensitivity to drugs.
Diagram of vasculitides categorized based on frequently affected vessel size and types
The term vasculitis covers a group of conditions characterized by
inflammation of the vessel wall resulting in narrowing or occlusion of the lumen, aneurysm formation, and impairment of distal organ function.
Purpura involving the lower extremities in a child with Henoch-Schönlein purpura/ IgA vasculitis
Leukocytoclastic vasculitis with ulceration in a patient with rheumatoid arthritis.
Livedo reticularis is a skin symptom.
It refers to a netlike pattern of reddish-blue skin discoloration.
The legs are often affected.
The condition is linked to swollen blood vessels.
It may get worse when the temperature is cold.
Severe necrotizing scleritis in a patient with
new- onset granulomatosis with polyangiitis (GPA).
Multiple pulmonary nodules in a patient with newly presenting GPA as seen on plain chest radiography.
Digital gangrene in a patient with acute- onset vasculitis.
