Eruptions in life-threatening rheumatologic
diseases
Burhan Engin, MD
a,⁎
, Ay
şegül Sevim, MD
b, Seher Küçüko
ğlu Cesur, MD
c,
Yalç
ın Tüzün, MD
daDepartment of Dermatology and Venereology, Cerrahpaşa Medical Faculty, Istanbul University-Cerrahpaşa, Istanbul, Turkey bDepartment of Dermatology and Venereology, Haydarpasa Numune Research and Teaching Hospital, Istanbul, Istanbul, Turkey cDepartment of Dermatology and Venereology, Altınbaş University, Bahçelievler Medical Park Hospital, Istanbul, Istanbul,
Turkey
dDepartment of Dermatology and Venereology, Bahçelievler Medical Park Hospital, Istanbul, Istanbul, Turkey
Abstract Dermatologic changes occur in a variety of rheumatic diseases. Skin can be the initial site of in-volvement, thus providing important clues for an accurate diagnosis based on cutaneousfindings. Dermato-logicfindings can also be an indicator of systemic involvement and prognostic outcome; however, many connective tissue disorders have a wide variety of cutaneous manifestations, with significant overlap be-tween different diseases. These skin signs often precede systemic clinical manifestations. Careful attention to characteristic dermatologicfindings in Behçet’s disease, systemic lupus erythematosus, rheumatoid arthri-tis, and various vasculitis can provide prompt therapeutic approaches in the case of life-threatening compli-cations of systemically involved rheumatologic diseases.
© 2019 Elsevier Inc. All rights reserved.
Introduction
Many patients with rheumatologic disorders either present with an eruption or develop an eruption in the course of the dis-ease. Many autoimmune connective tissue diseases and vascular conditions in rheumatology have cutaneous manifestations. Skin signs are useful in the diagnosis of rheumatic diseases, as they of-ten precede systemic clinical manifestations. They can also act as a prognostic marker and predict systemic involvement. In rare cases, rheumatologic diseases may cause serious or life-threatening conditions, which may be diagnosed with the help of the cutaneousfindings of the diseases. In each section, we
have concentrated on the acute, severe, or life-threatening cuta-neous manifestations of a rheumatologic entity with an algorithm that incorporates a differential diagnostic approach.
Behçet
’s disease
Behçet’s disease (BD) is classified among the vasculitides and the pathophysiology is thought to be autoimmune, although some suggest it is an autoinflammatory disease. Human leukocyte antigen (HLA)-B51 is recognized as a genetic factor. Hyperfunction of neutrophils, reactive oxygen species production, T-cell abnormalities, and heat shock proteins (microbial and viral) are all involved in the etiopathogenesis.
⁎ Corresponding author.
E-mail address:burhanengin2000@yahoo.com(B. Engin).
https://doi.org/10.1016/j.clindermatol.2019.10.016
BD is a multisystemic, autoinflammatory vasculitis. A complex genetic background, coupled with innate and adap-tive immune system activation, causes the diverse clinical manifestations that characterize the clinical picture.1As a
mul-tisystem disease, clinical manifestations can involve nearly all systems of the body.2BD manifestations are self-limiting but
recurrent. Some heal without a sequela, but others are the main cause of morbidity, such as ophthalmologic manifestations leading to blindness if not aggressively treated. Some may cause mortality, as in some of the vascular, neurologic, car-diac, or pulmonary involvements. There is no single laboratory finding or pathognomonic diagnostic tool for BD, so the diag-nosis mainly depends on the clinical features and various sets of criteria, most of which are comprised of mucocutaneous findings. As a result, it is important to know the pathogno-monic skinfindings of BD for early intervention and possible prevention of fatal complications.
Recurrent aphthous stomatitis (RAS) is one of the most common clinical features of BD. It usually presents as an ini-tial sign of the disease, but it can also develop during the course of the disease after the appearance of other signs and clinical manifestations. In a retrospective analysis, some signs of the disease become apparent many years after the develop-ment of aphthous stomatitis.3Aphthae can be seen anywhere
on the nonkeratinized mucosal membranes of the mouth, but the mucosal surface of the lips, the buccal mucosa, or on the lateral tongue are the most common locations. It begins as a painful papule and becomes rapidly ulcerated. A white to yel-lowish pseudomembrane covers the surface of the ulcer, and there is an erythematous halo surrounding the lesion.
Another cardinal sign of BD is a genital ulcer. Men usually have ulcers on the scrotum, inguinal region, and penis, whereas women have inguinal and vulvar ulcers. The ulcer starts as a painful papule or pustule with necrosis soon appear-ing. It has a punched-out appearance with an edematous bor-der and afibrin layer on the floor.
Erythema nodosum-like lesions are localized symmetri-cally on the lower extremities, as well as on the thighs and sa-cral region. These painful nodules may be 1 to 5 cm in diameter. Superficial thrombophlebitis migrans is another form of a nodular lesion seen in BD, being more frequent in men. Dusky, red nodules are usually located on the medial side of the legs. Superficial thrombosis can present itself as a palpa-ble mass along the course of the veins and is thought to be re-lated to deep vein thrombosis.4
Acneiform lesions are polymorphous in nature. In flamma-tory papules, pustules, and cysts can accompany nonin flamma-tory lesions, including comedones. These acneiform lesions are mostly located on the back, chest, shoulders, and, less com-monly, on the face. Sweet syndrome can be seen during the course of the disease in BD patients in approximately 4% of cases. Painful, erythematous nodules and papules emerge on the facial areas and extremities. Aphthous ulcers, arthritis, and uveitis can also be components of Sweet syndrome.5
Extragenital ulcers are very rare in Behçet’s disease, and they are located on the inframammarian folds, axillary region, and
interdigital area of the feet. Patients with a history of deep vein thrombosis are more prone to develop ulcus cruris (Figure 1) and vasculitis.
The most common multisystem involvement of BD is ocu-lar, causing uveitis, epididymitis, glaucoma, cataracts, and eventually optic nerve involvement, leading to irreversible loss of vision.6Up to 50% of BD patients have either arthritis or
ar-thralgia.7Enthesopathy usually accompanies arthritis.
Acnei-form lesions are also common findings in Behçet patients with arthritis. Papulopustular lesions and arthritis are together regarded as a cluster of disease expression. This cluster is fre-quently found in familial cases.8
BD involves both arteries and veins. The most frequent manifestation of vascular involvement is venous thrombosis in the lower extremities. In the case of superficial thrombo-phlebitis, erythema nodosum-like lesions present on the me-dial side of the leg along the course of the veins. There may be accompanying deep femoral vein thrombosis or inferior vena cava syndrome. Recurrent thrombosis may lead to chronic venous insufficiency and venous claudication.9
Vena cava thrombosis has variable clinical signs and clini-cal manifestations according to the level of obliteration. With the superior vena cava syndrome, there is edema in the head and neck region, along with jugular venous distention, whereas the inferior vena cava syndrome may lead to edema in the lower extremities, stasis dermatitis, and leg ulcers. Budd-Chiari syndrome is a rare but potentially fatal complica-tion of BD. Hepatic vein thrombosis results in ascites forma-tion together with abdominal pain, edema of the lower extremities and scrotal area, and even hepatic failure in severe cases.10
Arterial involvement can also be seen as aneurysms, mostly in the pulmonary artery, peripheral arteries, or abdominal aorta; however, pulmonary artery involvement is rather rare (5%), presenting with either an aneurysm or thrombosis. The mainfindings of pulmonary artery aneurysm are fever, chest pain, cough, dyspnea, and hemoptysis.11Arterial aneurysms
can also be observed in the peripheral arteries, including the femoral, iliac, popliteal, and carotid artery, as well as the
dominal aorta. The rupture of these aneurysms is a major cause of mortality.12
Cardiac involvement is rare in Behçet patients, but intracar-diac thrombosis can lead to death.13Gastrointestinal
involve-ment of BD is usually mild, but gastrointestinal bleeding with ulcers located in the terminal ileum, cecum, and colon re-gion may be observed.14 In the case of nervous system
in-volvement, parenchymal involvement of the brain and cerebral venous thrombosis with accompanying vasculitis are the most common forms of presentation, leading to dural sinus thrombosis, severe headaches, papilledema, and motor or ocu-lar nerve paralysis due to elevated intracranial pressure.15
Lupus erythematosus
About 25% of patients with systemic lupus erythematosus (SLE) initially present with skin involvement. The diagnosis of SLE is mainly based on a set of diagnostic criteria and, ac-cording to the American College of Rheumatology, almost half of those criteria are skin signs, namely malar/butterfly eruption, discoid plaques, photosensitivity, and oral ulcers. In nearly 70% of patients, skin disease presents at some time in the course of the disease, most commonly preceding sys-temic involvement, leading to extensive arthritis or serositis, end-stage renal insufficiency, or central nervous system dis-ease. Correctly classifying cutaneous lupus erythematosus (CLE) will help to determine the underlying type and severity of SLE and enable early and aggressive treatment of the sys-temic involvement, which is associated with a high mortality. CLE includes three subsets: acute cutaneous lupus erythe-matosus (ACLE), subacute cutaneous lupus erytheerythe-matosus (SCLE), and chronic cutaneous lupus erythematosus (CCLE). ACLE is a manifestation of SLE that may present as a charac-teristic localized facial eruption, less commonly as a general-ized eruption, and rarely as a toxic epidermal necrolysis-like presentation.16Almost all patients with ACLE have systemic
involvement; thus, it is of vital importance to recognize the specific skin findings for this type of CLE. The localized facial eruption, also known as“malar eruption” or “butterfly erup-tion,” is characterized by erythema over the cheeks and the bridge of the nose but the nasolabial folds are spared. Local-ized ACLE may precede other clinical manifestations of SLE by months or even years or may be accompanied by other clin-ical manifestations and signs of acute SLE. The involved skin feels warm and appears slightly edematous, being exacerbated by sun exposure. A generalized erythematous maculopapular and morbilliform eruption involving sun-exposed skin areas, mostly extensor surfaces of the arms and hands, may also be observed. Notably, the skin overlying the small joints of the hand is spared, unlike dermatomyositis. Severe cases may present with widespread vesicles or bullae, resembling toxic epidermal necrolysis.17
With SCLE, approximately 10% to 15% of patients go on to develop severe clinical manifestations of SLE, such as
serious central nervous system or renal disease.18SCLE
be-gins as small, erythematous, slightly scaly papules that evolve into either psoriasiform or annular erythematous plaques with scale, predominantly affecting the shoulders, forearms, and neck. Despite the photo-aggravated nature of the condition, the face is often spared.19Drug-induced SCLE tends to be
more severe or widespread with a bullous or vasculitic compo-nent and exhibits a higher predilection for the facial area.
CCLE is comprised of various subtypes:
• Discoid lupus erythematosus (DLE): the most common type, accounting for 73% to 85% of CCLE.20
• Lupus erythematosus tumidus • Lupus profundus (lupus panniculitis) • Chilblain lupus erythematosus
• Lichenoid cutaneous lupus erythematosus: lichen planus overlap syndrome.
DLE is also rather common during the course of SLE. The presence of DLE lesions among patients with SLE may mod-ify the risk of specific features of the systemic disease. Patients with DLE have an increased risk for photosensitivity and leu-kopenia but a decreased risk for serositis and arthritis. The classic findings of DLE are erythematous and indurated, well-demarcated plaques covered by a well-formed adherent scale that become hyperkeratotic leading to atrophy and scar-ring with hyperpigmentation and/or hypopigmentation. There is follicular involvement, causing reversible and irreversible (scarring) alopecia.21DLE most often involves the face, neck,
and scalp but may also occur on the ears, particularly the con-chal bowls. Hypertrophic or verrucous LE, a rare form with se-vere hyperkeratosis of extensor surfaces of arms, upper back, and face, and mucosal LE are other forms of CCLE. Cutane-ous LE may also present as panniculitis (ie, lupus profundus). Additionalfindings may include Raynaud phenomenon, leu-kocytoclastic vasculitis, thromboembolic vasculopathies, and livedo reticularis.
Dermatomyositis
Dermatomyositis (DM), also referred to as idiopathic in-flammatory myopathy, is an autoimmune disorder affecting the skin and musculature. It is a multisystem disorder with car-diac, pulmonary, and esophageal involvement. Cardiac dis-ease has a broad spectrum, from conduction abnormalities and arrhythmias to myocardial infarction and congestive heart failure.22Esophageal involvement causes dysphagia,
regurgi-tation, or even aspiration pneumonias due to esophageal dys-motility. Respiratory insufficiency may result from diaphragmatic and chest wall muscle weakness. Occurrence of interstitial lung disease may be associated with rapidly pro-gressive pulmonary failure and death.23There is also an
in-creased risk of associated malignancies. Skin manifestations can give a clue about the diagnosis of DM; thus appropriate
cancer screening tests can be done along with necessary mea-sures regarding systemic complications.
Gottron papules and the heliotropic eruption are the hall-mark of DM. Gottron papules are erythematous to violaceous papules, sometimes with scaling or ulceration, occurring sym-metrically over the extensor areas of the metacarpophalangeal and interphalangeal joints. The Gottron sign is defined as ery-thematous to violaceous macules, patches, or papules on the extensor surfaces of elbows, knees, or ankles.24Gottron
pap-ules and the Gottron signs are hallmark skin signs of dermato-myositis, which may differentiate DM from CLE.
The heliotrope eruption is an erythematous to violaceous eruption on the upper eyelids and periorbital area. Patients may also have accompanying facial erythema, erythema (Figure 2), and poikiloderma of photo-exposed areas (dyspig-mentation, telangiectasias, and epidermal atrophy), mostly on the V of the neck and the upper areas of the chest. These erup-tions are often associated with significant pruritus. Generalized erythroderma may also be observed and requires prompt atten-tion due tofluid and electrolyte imbalances. Abnormal capil-lary nail bed loops with periungual erythema and psoriasiform changes in scalp or calcinosis cutis are other rare findings.25
Systemic sclerosis
In systemic sclerosis (SS), the presence of thickened and hardened skin is accompanied by internal organ involvement including vessels, musculoskeletal, renal, pulmonary, cardiac, and gastrointestinal systems. The disease is associated with a high mortality and morbidity rate. Skin involvement is charac-terized by variable degrees of skin sclerosis. The fingers, hands, and face are generally affected and edematous swelling with erythema may precede skin induration.26
Pruritus may occur in the early stages. Otherfindings may include dyspigmentation, loss of appendicular hair, sclerodac-tyly (Figure 3), digital ulcers, pitting at thefingertips, telangi-ectasia, and calcinosis cutis. According to the degree of skin
involvement, SS has two forms: a localized form and a gener-alized form. The locgener-alized form affects the hands, the distal forearm, and, to a lesser extent, the face and neck. These pa-tients generally have prominent vascular manifestations, in-cluding severe Raynaud phenomenon and cutaneous telangiectasia. Many patients may have manifestations of the CREST syndrome (Calcinosis cutis, Raynaud phenomenon, Esophageal dysmotility, Sclerodactyly, and Telangiectasia). Sclerotic skin on the chest, abdomen, or upper areas of the arms and shoulders is indicative of the diffuse form. Such pa-tients are more likely to develop internal organ damage due to ischemic injury orfibrosis. Pulmonary fibrosis and related pul-monary arterial hypertension, cardiac disease, and renal crisis are commonly observed.27There have been several reports
demonstrating an increased risk of malignancy in patients with SS, and the most significant association appears to be with lung cancer.28
Rheumatoid arthritis
Rheumatoid arthritis (RA) is a chronic, systemic, in flam-matory disorder of unknown etiology that primarily involves synovial joints. The arthritis is typically symmetrical and usu-ally leads to the destruction of joints due to erosion of cartilage and bone, causing deformities. Involvement of the organs such as skin, eye, lung, heart, kidney, blood vessels, salivary glands, central and peripheral nervous systems, and bone marrow oc-curs in about 40% of patients with RA over a lifetime of dis-ease.29Pulmonary involvement in RA may include pleurisy
and parenchymalfibrosis or nodules and bronchiolitis obliter-ans. Cardiac involvement, such as clinically apparent pericar-ditis and myocarpericar-ditis, and the presence of rheumatoid nodules in the pericardium, myocardium, or valvular struc-tures, and an increased risk of coronary artery disease, heart failure, and atrialfibrillation may be observed. Vascular dis-ease can take several forms in patients with RA, and vasculitis of small to medium blood vessels can occur.30
The seven criteria of RA are as follows: • Morning stiffness
• Arthritis of 3 or more joint areas • Arthritis of hand joints
• Symmetric arthritis • Rheumatoid nodules
• Reactive serum rheumatoid factor (RF)
• Radiographic changes (ie, erosions and bone decalcifications) Rheumatoid nodules are one of the seven criteria for RA and are the most common cutaneous manifestation.31Palpable
nodules are present in up to 20% to 35% of patients with RA at some point during their disease course.32Rheumatoid factor is
almost always present in patients with nodules. Nodules are subcutaneous,firm, painless lesions over extensor surfaces of the skin as well as heart, lung, and muscle and may be compli-cated by ulceration, bursitis, synovial rupture, and gangrene. In the case of accelerated rheumatoid nodulosis, painful nod-ules are observed on the hands due to methotrexate therapy. Raynaud phenomenon is another common association of RA. Rheumatoid vasculitis may present with purpura, splinter hemorrhages, nail fold infarcts, and peripheral neuropathy. Ul-cerative lesions may result from venous stasis, arterial insuf fi-ciency, neutrophilic infiltration, and/or vasculitis.33Chronic
ulcers in patients with RA have unsteady prognosis and may result in serious complications when associated with vasculi-tis, causing increased risk of mortality.34
Rheumatoid neutrophilic dermatosis is rarely seen with asymptomatic red urticated papules and plaques on forearms and hands. Other rare cutaneous manifestations are erythema elevatum diutinum, livedo reticularis, digital infarcts, atrophie blanche, hemorrhagic blisters, and necrotizing granulomatous vasculitis.
Sjögren syndrome
Sjögren syndrome (SS) is a systemic autoimmune disorder that primarily reduces the function of the sweat glands and mu-cous glands, causing the characteristic sicca clinical manifesta-tions. It can either occur in a primary form not associated with other diseases or a secondary form that complicates or over-laps with other rheumatic conditions, most commonly RA and SLE. In both primary and secondary SS, decreased exo-crine gland function leads to a combination of dry eye (kerato-conjunctivitis sicca) and dry mouth (xerostomia).35 Many
organs, other than the exocrine glands, may be affected in pa-tients with SS, including the skin and joints; the lungs, heart, and gastrointestinal tract; the pancreas and liver; the kidneys, bladder, and gynecologic system; and both the peripheral and central nervous systems. Additionally, hematologic abnor-malities are often present, and there is an increased risk of lym-phoproliferative disorders.
The major skinfindings include xerosis, purpura associated with vascular or hematologic abnormalities, Raynaud
phenomenon, cutaneous vasculitis, annular erythema, ery-thema nodosum, eryery-thema multiforme, eyelid dermatitis, and angular cheilitis.36
Relapsing polychondritis
Relapsing polychondritis is an immune-mediated condition associated with inflammation in cartilaginous structures and other tissues throughout the body, particularly the ears, nose, eyes, joints, and respiratory tract. Approximately one-third of patients have another disease, usually some form of systemic vasculitis, a connective tissue disorder, or myelodysplastic syndrome.37The clinical features vary in severity and
dura-tion, both at presentation and throughout the course of the ill-ness. Auricular involvement is the most common feature, but costal cartilage, eyes, nose, airways, heart, vascular system, skin, joints, kidney, and nervous system can also be in-volved.38Involvement of the cartilaginous tissue of the larynx,
trachea, and bronchi can sometimes cause significant obstruc-tive respiratory disease, sleep apnea syndrome, and postob-structive pneumonias.
Skin signs in relapsing polychondritis are nonspecific; they are not diagnostic criteria, nor are they associated with disease severity. Unilateral or bilateral external ear inflammation that characteristically spares the earlobe is typical. Auricular in-flammation and resulting ear cartilage swelling, erythema and pain, nasal pain, rhinorrhea, epistaxis due to nasal cartilage inflammation, and, in severe cases, saddle-nose deformity may be observed. Nonspecific vasculitic signs, nodules on the ex-tremities, purpura, aphthous ulcers, papules, livedo reticularis, ulcers, and distal necrosis are other rare skinfindings.
Psoriasis
Psoriasis is a complex and multifactorial inflammatory dis-ease that involves hyperproliferation of the keratinocytes in the epidermis with an increase in the epidermal cell turnover rate. It has a chronic course with variable complications including metabolic syndrome, cardiovascular morbidity, joint manifes-tations, and psychiatric comorbidities; however, psoriasis is seldom thought of as a life-threatening condition. Neverthe-less, there are rare cases where aflare-up can be a medical emergency, as in erythrodermic psoriasis and generalized pus-tular psoriasis (Figure 4), causing fever,fluid loss, and other systemic manifestations.
Pustular psoriasis develops independently or in association with pre-existing psoriasis and may occur in a generalized or localized distribution. Localized forms primarily affect the palms, soles, or extremity digits. Generalized pustular psoria-sis presents as an acute, widely distributed eruption of pustules arising on inflamed, erythematous skin over the trunk and limbs. Painful erythematous patches or thin plaques rapidly become studded with numerous pinhead-sized sterile pustules. Annular or figurate erythematous plaques with peripheral
pustules and scale can also be observed. The pustules resolve within several days, leaving erythema and extensive scaling.39
Mucosal involvement, manifesting as oral pustules or geo-graphic tongue, can accompany the cutaneousfindings. Epi-sodes are accompanied by fever, chills, and malaise, and patients appear systemically ill. Other extracutaneous clinical manifestations include arthralgias, lower extremity edema, jaundice, and ocular abnormalities such as conjunctivitis, iritis, or uveitis.40Complications of generalized pustular psoriasis
may be life-threatening. Potential complications include sep-sis; serious renal, hepatic, or respiratory abnormalities such as acute respiratory distress syndrome; and death.
Erythrodermic psoriasis is an uncommon, severe variant of psoriasis that is characterized by widespread erythema of the skin. The hallmark of erythrodermic psoriasis is the development of widespread, confluent erythema of the skin, developing rap-idly or in a more gradual manner. According to different sources, the percentage of body surface area involvement required for a patient to be considered erythrodermic ranges from 75% to 90%.41The skin is often painful and pruritic, particularly in
areas with prominent scaling. Photosensitivity may also be present. Associated extracutaneousfindings may include fe-ver, chills, malaise, tachycardia, arthralgias, and lymphade-nopathy. Laboratory abnormalities may include leukocytosis, eosinophilia, and anemia. Associated nail disorders such as pitting, nail dystrophy, and onycholysis may be observed. Potential complications of erythrodermic psoriasis include he-modynamic, thermoregulatory, and metabolic disturbances; electrolyte imbalances; cutaneous or systemic infections, par-ticularly staphylococcal septicemia; and acute respiratory dis-tress syndrome.42
Vasculitis
Systemic vasculitis is defined by the presence of inflamma-tory leukocytes in vessel walls with reactive damage to mural structures and resulting tissue ischemia and necrosis. In
general, affected vessels vary in size, type, and location in as-sociation with the specific type of vasculitis. The exact patho-genetic mechanisms underlying these diseases are unknown. They are often serious and sometimes fatal, requiring prompt recognition and therapy. Skin signs are common in many kinds of vasculitis due to their abundant vasculature. Most of the common cutaneousfindings of these vasculitis include pal-pable purpura, livedo reticularis, infiltrative erythema, ulcers, and digital ischemia (Figure 5). These skin signs prompt an in-vestigation for any systemic involvement of vasculitis; how-ever, the skin signs alone are not sufficient for diagnosis of a specific condition.
Small vessel vasculitis presents with palpable purpura, usu-ally more pronounced on gravity-dependent areas, with associ-ated edema. One example for this group is antineutrophil cytoplasmic antibody (ANCA)–associated spell out vasculitis. It is a necrotizing vasculitis with granulomatous inflammation and is potentially lethal. Skin signs include palpable purpura, panniculitis and nodules, gingival hyperplasia, ulcers, and pyoderma gangrenosum-like lesions. Microscopic polyangii-tis, granulomatosis with polyangiipolyangii-tis, and Churg-Strauss are the major clinicopathologic variants of ANCA-associated vas-culitis. In the case of microscopic polyangiitis, the most com-mon skin lesion is leukocytoclastic angiitis, which causes purpura involving the lower extremities that may be accompa-nied by splinter hemorrhages, necrosis, and ulceration. Skin le-sions may also include urticaria, livedo reticularis, and nodules.43
Of patients with granulomatosis with polyangiitis, 30% to 46% present with dermatologic manifestations.44These
mani-festations include palpable purpura, papules, vesicles, subcuta-neous nodules, plaques, and ulcers, which may resemble pyoderma gangrenosum. Involvement of the digital arteries may cause gangrene. The lesions are typically located on the lower extremities, but they can also manifest on the face, upper extremities, and the extensor surfaces of the joints. Oral and nasal ulcerations may also occur. Skin lesions are usually in-dicative of an active systemic disease.
Skin involvement is one of the most common features of Churg-Strauss disease (eosinophilic granulomatosis with
poly-Fig. 4 Pustular psoriasis.
angiitis [EGPA]). Half to two-thirds of patients with EGPA have skin lesions, which usually appear as tender subcutane-ous nodules, mainly granulomas, on the extensor surfaces of the arm, particularly the elbows, hands, and legs.45 These
ANCA-associated vasculitic diseases may have high mortality due to renal glomerular involvement or lower respiratory tract inflammation.
Immune complex small-vessel vasculitis refers to vasculitis with vessel wall deposits of immunoglobulin and comple-ments. Glomerulonephritis is often present, being the major cause of morbidity and mortality. In case of cryoglobulinemic vasculitis, cold-precipitated polyclonal immunoglobulins are deposited. Purpura at distalfingers and toes is a hallmark sign. Raynaud phenomenon, livedo reticularis, ulceration, acrocya-nosis, and gangrenes may accompany it, and the disease is al-most always coupled with glomerulonephritis.
Urticarial vasculitis is a leukocytoclastic vasculitis; however, hypocomplementemic urticarial vasculitis is associated with ur-ticaria and hypocomplementemia. The presence of anti-C1q an-tibodies is one of the most distinctivefindings and leads to the formation of immune complexes. Skin signs are tender, burn-ing, and painful papules or wheals that persist for 24 to 72 hours. Glomerulonephritis, arthritis, obstructive pulmonary disease, and ocular inflammation may also be observed.46
Henöch–Schonlein purpura (HSP) is a systemic vasculitis characterized by the tissue deposition of IgA1 immune com-plexes affecting mostly small vessels. It usually occurs in chil-dren after a respiratory tract infection. The eruption often begins with erythematous, macular, or urticarial wheals but can also can have less typical presentations including targetoid lesions.47It is symmetrically distributed and located primarily
in pressure areas such as the lower extremities. The disease can cause arthritis, glomerulonephritis, intestinal vasculitis, and in-tussusception, which can result in serious morbidity and even mortality.
Thromboangiitis obliterans (Buerger disease) is a vasculop-athy due to thrombosis of small or medium vessels associated with smoking. The disease is characterized by segmental in-flammatory thrombotic vessel occlusions.48Patients are
pre-dominantly young smokers who present with painful purple or bluefingers and toes, often asymmetrical, due to distal ex-tremity ischemia, ischemic digit ulcers, or digital gangrene. Ulcerated lesions may become gangrenous, leading to amputa-tion of parts of an arm or leg.
Polyarteritis nodosa (PAN) and Kawasaki disease affect mainly medium-sized arteries. PAN is a systemic necrotizing vasculitis and skin signs include bright red or violet subcutane-ous nodules that become confluent and painful, livedo reticularis, ulcers on the legs, and postinflammatory hyperpigmentation.49
Patients typically present with systemic clinical manifesta-tions, and the disease may cause hypertension, renal insuf fi-ciency, or neurologic dysfunction.
Kawasaki disease is one of the most common vasculitides of childhood.50The clinical features reflect widespread
in-flammation of primarily medium-sized muscular arteries. Complications, such as coronary artery aneurysms, depressed
myocardial contractility and heart failure, myocardial infarc-tion, arrhythmias, and peripheral arterial occlusion may de-velop and lead to significant morbidity and mortality. Skin signs include polymorphous exanthem (mostly on the trunk and proximal extremities), macular eruption and desquamation of the perineal area, edema and erythema of palms and soles, and periungual desquamation and oral mucosalfindings such as dry and cracked“cherry” lips and “strawberry” tongue with hypertrophied papillae and hyperemia.51
Giant cell arteritis, also known as temporal arteritis, dominantly affects the aorta and its major branches, with a pre-dilection for the branches of the carotid, including the superficial temporal artery. The onset of disease usually occurs in patients older than 50 years of age. Systemicfindings are frequent and include fever, fatigue, and weight loss. Specific findings related to involvement of characteristic arteries may be present, including headache, jaw claudication, and even vi-sion loss. Temporal arteries can be abnormal to palpation. Skin signs include cyanosis and pallor of the extremities, scalp ten-derness, and, sometimes, necrosis.
Conclusions
Autoimmune connective tissue diseases and vascular con-ditions may present with cutaneous manifestations. Such skin signs often precede systemicfindings, making them useful in diagnosing rheumatic diseases, providing prognostic markers, and predicting systemic involvement. As these conditions may cause serious and even life-threatening events, the help from the skinfindings are of vital importance.
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