Cutaneous Rheumatology

The spectrum of disorders traditionally considered to be cutaneous rheumatology includes: lupus erythematosus ( Ch. 41 ); dermatomyositis ( Ch. 42 ); systemic sclerosis ( Ch. 43 ); vasculitides ( Ch. 24 ); and miscellaneous disorders. Miscellaneous disorders usually include: rheumatoid arthritis ( Ch. 45 ), reactive arthritis (formerly Reiter disease) ( Ch. 8 ), psoriatic arthritis ( Ch. 8 ), Behçet disease ( Ch. 26 ), pyoderma gangrenosum ( Ch. 26 ), Sweet syndrome ( Ch. 26 ), bowel-associated dermatosis–arthritis syndrome ( Ch. 26 ), Kawasaki disease ( Ch. 81 ), relapsing polychondritis ( Ch. 45 ), and several of the autoinflammatory disorders (see Table 45.7 ).

Cutaneous conditions reported in patients with rheumatoid arthritis are summarized in Table 53.1 ( Figs 53.1–53.5 ) . Dermatologists should be particularly careful in this group of patients to couple laboratory evaluation with a comprehensive cutaneous examination, including all mucosal surfaces, nails, nail folds, and hair. Clinical criteria are published for the diagnosis of many of these disorders; dermatologists should be familiar with these criteria and incorporate them into a focused, thorough history, which includes relevant negatives. It is very helpful to consider the clinicopathologic basis and pathogenesis of cutaneous lesions. For example, patients with systemic lupus erythematosus can have different types of photodistributed lesions with an interface histopathology, e.g. discoid, subacute, poikilodermatous, and they have different implications with regard to systemic disease. Such lesions are also treated differently than those caused by vessel-based pathology, e.g. small or larger vessel vasculitis.

Rheumatoid papules.

Multiple red–brown papules, some with scale-crust, on the lower extremity. This entity is within the spectrum of palisaded neutrophilic and granulomatous dermatitis (see Table 53.1 ).

Annular variant of interstitial granulomatous dermatitis (IGD).

This clinical presentation with annular plaques on the medial thighs is often seen in the setting of rheumatoid arthritis. Of note, IGD has also been implicated as a side effect of medications, including calcium channel blockers, TNF-α inhibitors, and HMG-CoA reductase inhibitors (“statins”).

Superficial ulcerating rheumatoid necrobiosis.

Shiny, yellow plaques with red–brown edges and areas of ulceration that clinically resemble necrobiosis lipoidica. This patient had active rheumatoid vasculitis.

Bywaters lesions.

Tender, purpuric papules on the distal fingers in a patient with rheumatoid vasculitis. Histologically, leukocytoclastic vasculitis is seen.

Pseudoporphyria in a patient with rheumatoid arthritis.

The cause was a nonsteroidal anti-inflammatory drug.

Courtesy, Kalman Watsky, MD.

Sjögren syndrome is an autoimmune disorder that is characterized by keratoconjunctivitis sicca and xerostomia (see Table 45.4 ). In primary Sjögren syndrome, vascular inflammation within the skin (e.g. small vessel vasculitis, hypergammaglobulinemic purpura) can occur even before the clinical diagnosis of Sjögren syndrome has been established. Some patients from the Far East, including Japan and the Philippines, have been described with “annular erythema of Sjögren syndrome”. There is ongoing debate as to whether this disorder is unique to Sjögren syndrome or if it is, in fact, a form of subacute cutaneous lupus erythematosus . Secondary Sjögren syndrome occurs in patients with other rheumatologic diseases, including rheumatoid arthritis, dermatomyositis and systemic sclerosis. It is important to remember that the diagnosis of Sjögren syndrome is one of exclusion, and that other conditions can cause xerostomia/xerophthalmia, including chronic GVHD, sarcoidosis, primary systemic amyloidosis, hepatitis C viral infection, and HIV disease.

Cutaneous Hematology and Oncology

Disorders of mutual interest to the dermatologist and hematologist/oncologist are well covered in the following chapters of this textbook: metastatic disease ( Ch. 122 ), leukemia/lymphoma ( Chapter 119 , Chapter 120 , Chapter 121 ), dysproteinemias ( Ch. 119 ), histiocytoses ( Ch. 91 ), vascular neoplasms ( Ch. 114 ), cutaneous T-cell lymphoma ( Ch. 120 ), melanoma ( Ch. 113 ), and cutaneous reactions to chemotherapeutic agents ( Ch. 21 ). Skin signs of internal malignancy are summarized in Tables 53.2 and 53.3 .

Bazex syndrome (acrokeratosis paraneoplastica).

A Acral psoriasiform lesions that have a violaceous hue, accompanied by nail dystrophy. The patient had a squamous cell carcinoma (SCC) of the tonsillar pillar. B Thin hyperpigmented plaques of the helix and antihelix in a patient with SCC of the pharynx.

B, Courtesy, Jean L Bolognia, MD.

Erythema gyratum repens.

This patient had cancer of the breast.

Paraneoplastic pemphigus.

Lesions that resemble bullous pemphigoid in a patient with immunopathologic confirmation of paraneoplastic pemphigus despite an underlying malignancy not having been detected.

Acute febrile neutrophilic dermatosis (Sweet syndrome).

Vesicopustules with surrounding erythema on the dorsal hand in a patient with myelodysplastic syndrome.

POEMS syndrome.

This patient had multiple angiomas on his trunk as well as his face and scalp. All the angiomas that were examined histologically were glomeruloid hemangiomas. In addition, he reported a recent 10 lb (4.5 kg) weight loss, impotence and fatigue, and was found to have a neuropathy, adult-onset diabetes, hypothyroidism, and peripheral edema. His underlying disorder was an osteosclerotic myeloma.

Multicentric reticulohistiocytosis.

Multiple nodules are present on the dorsal hands in this adolescent. This patient did not have a malignancy.

Both disease-specific and nonspecific skin lesions have been reported in association with myelodysplastic syndrome (MDS) . The former include leukemia cutis and “cutaneous myelodysplasia”; the latter is characterized by an infiltrate of atypical myeloid cells in a patient who does not fulfill the criteria for leukemia. The most commonly associated skin findings include neutrophilic dermatoses and vasculitis. A unique form of Sweet syndrome, which is preceded by a dense perivascular lymphocytic infiltrate, has been described in a few small cohorts of patients with MDS and may portend a poorer prognosis . Generalized granulomatous dermatitis, a variety of autoimmune disorders, including Behçet disease, relapsing polychondritis and bullous pemphigoid, and panniculitis have also been reported. In some patients, these cutaneous disorders precede the diagnosis of MDS, serving as its harbinger. Recurrence of skin lesions, or their lack of response to therapy, may herald progression to leukemia.

An eczematous or psoriasiform plaque of the nipple and surrounding skin can be seen in Paget disease due to epidermal extension of an underlying ductal adenocarcinoma of the breast ( Fig. 53.12 ). While extramammary Paget disease (EMPD) most commonly represents a primary intraepithelial adenocarcinoma (>75% of patients; Fig. 53.13 ), secondary EMPD can be due to an underlying visceral malignancy, e.g. colon, bladder (see Fig. 73.16 ).

Paget disease of the breast.

A chronic, erythematous plaque surrounds the nipple.

Courtesy, Robert Hartman, MD.

Extramammary Paget disease.

Eroded erythematous plaque with exudate, especially in the inguinal crease. The patient refused any further evaluation and had never undergone colonoscopy or cystoscopy.

Acanthosis nigricans is characterized by velvety hyperpigmentation of the intertriginous surfaces and, less often, extensor surfaces ( Figs 53.14 & 53.15 ). Although this disorder may be associated with an internal malignancy (most frequently gastric adenocarcinoma), it is most often associated with insulin resistance . The areas most frequently affected are the neck and axillae, but can include any skin fold, including that of the lower lip and chin. Malignancy-associated acanthosis nigricans is usually rapid in onset and may be accompanied by skin tags, multiple seborrheic keratosis, or tripe palms. Verrucous changes of the lips may also develop, and weight loss is common. In contrast, acanthosis nigricans associated with endocrine dysfunction is more insidious in onset and less widespread, and the patients are often overweight or obese. In either instance, there are probably one or more circulating factors that stimulate the epidermal proliferation (i.e. papillomatosis) that is observed histopathologically. An approach to the patient with acanthosis nigricans in outlined in Fig. 53.16 . Treatment of the underlying malignancy, or effective treatment of the endocrinopathy, including weight loss and use of insulin sensitizers, may result in improvement or disappearance of the acanthosis nigricans. Recurrence of malignancy-associated acanthosis nigricans requires a search for recurrent cancer.

Acanthosis nigricans.

A Involvement of the posterior neck in a young woman with obesity and insulin resistance. There is also an acrochordon. B Axillary involvement in an obese 10-year-old Filipino boy with insulin resistance and a strong family history of type 2 diabetes mellitus.

B, Courtesy, Julie V Schaffer, MD.

Acanthosis nigricans (AN) of the hands.

A Changes of AN overlie the knuckles in a patient with insulin resistance and obesity; acanthosis nigricans can involve extensor surfaces as well as flexural areas. B Diffuse involvement of the dorsal aspect of the fingers. Evaluation for an internal malignancy is recommended in patients with this type of clinical presentation.

A, Courtesy, Jean L Bolognia, MD; B, Courtesy, Joyce Rico, MD.

Evaluation of the patient with acanthosis nigricans (AN).

FGFR, fibroblast growth factor receptor; HAIR-AN, hyperandrogenemia, insulin resistance, acanthosis nigricans; INSR, insulin receptor; SADDAN, severe achrondroplasia with developmental delay and AN.

The glucagonoma syndrome is characterized by the development of necrolytic migratory erythema (NME), adult-onset diabetes mellitus, weight loss, and glossitis. These patients are also frequently anemic, and personality changes may occur. Skin lesions of NME are eroded, erythematous patches and plaques that characteristically involve the intertriginous areas, face (especially around the mouth), and distal extremities. Blisters may occur and lead to erythematous erosions. The eruption, which can be painful or pruritic, remits and recurs over the course of several weeks to months. It is frequently misdiagnosed as intertrigo or as seborrheic dermatitis. Histologically, pallor of the upper epidermis is highly suggestive of NME or a “nutritional” dermatosis (see Ch. 51 ). However, psoriasiform hyperplasia of the epidermis is often seen in NME and therefore clinicopathologic correlation is required.

Most, but not all, patients with NME have a glucagon-secreting tumor of the pancreas, and effective treatment of the tumor will result in a disappearance of the disease. Rarely, NME develops in the setting of severe liver disease. Similar skin lesions occur in patients with deficiencies of zinc, fatty acids or biotin (see Fig. 51.13 ) and replacement therapy leads to resolution of the cutaneous findings. The differential diagnosis of NME also includes necrolytic acral erythema (see below).

There is growing recognition of the role both inherited and acquired disorders of hypercoagulability or thrombophilia play in various skin disorders (see Chs 23 and 105 ). Some associations, such as those between protein C deficiency and neonatal purpura fulminans or prothrombin gene mutations and livedoid vasculopathy, are fairly well understood. However, there are other disorders in which cutaneous thromboses have been identified (e.g. calciphylaxis) where the precise role remains less well defined. Evaluation for hypercoagulability is warranted in patients with unexplained cutaneous thrombosis (see Table 105.9 ).

Cutaneous Endocrinology and Metabolic Disease

Cutaneous manifestations may provide important clues to the diagnosis of endocrine disorders, including diabetes mellitus . Patients with endocrine diseases are especially susceptible to a number of associated mucocutaneous disorders.

Diabetes mellitus is a very common medical condition that affects almost every organ system. Table 53.4 summarizes cutaneous manifestations of diabetes mellitus ( Figs 53.17–53.22 ). Further details are available in reviews on the subject .

Bullosis diabeticorum (diabetic bullae).

Non-inflammatory bullae on the lower extremity in a patient with diabetes mellitus.

Diabetic cheiroarthropathy (diabetic stiff hand syndrome).

Because of limited joint mobility and thickening of the skin of the hand, the patient is unable to appose the palms (“prayer sign”).

Courtesy, Jean L Bolognia, MD.

Diabetic dermopathy.

Note the brown macules and patches on the shins.

Courtesy, Jean L Bolognia, MD.

Eruptive xanthomas are frequently associated with poorly controlled diabetes mellitus.

This patient was first discovered to have diabetes following the appearance of these yellow–red papules.

Necrobiosis lipoidica.

This plaque on the shin has an inflammatory border and a yellow color with atrophy and telangiectasias centrally. Controversy exists about the exact risk of diabetes mellitus in such patients, but it is much more strongly associated with diabetes than is granuloma annulare.

Neuropathic ulcers on the toes of a patient with diabetic sensory neuropathy.

The primary characteristics of metabolic syndrome , previously known as syndrome X, are central obesity, hypertension, dyslipidemia, and type 2 diabetes. Almost all patients have insulin resistance, and it is associated with a high risk of cardiovascular disease. Clinical criteria for the diagnosis of metabolic syndrome are outlined in Table 53.5 . Women with polycystic ovary syndrome have a greater frequency of metabolic syndrome and often present with acanthosis nigricans, acne vulgaris, and hirsutism . An association between psoriasis vulgaris and metabolic syndrome has also been identified. Patients with moderate to severe psoriasis are at increased risk of atherosclerotic cardiovascular disease, which is linked to their propensity for the metabolic syndrome. The components of the metabolic syndrome – hyperlipidemia, diabetes mellitus, hypertension and obesity – are all established cardiovascular risk factors .

Thyroid disease is also associated with a significant number of dermatologic disorders. Several reviews have highlighted these dermatologic manifestations and associations , and they are summarized in Table 53.6 .

Adrenal disease classically manifests as excessive (Cushing syndrome) ( Figs 53.23 & 53.24 ) or insufficient (Addison disease) corticosteroid activity ( Fig. 53.25 ); this can include gluco- and mineralocorticoids. Excessive production of adrenal androgens may also occur (see Ch. 70 ). Features of these syndromes are outlined in Table 53.7 (see Ch. 125 ).

“Buffalo hump” of Cushing syndrome due to fat redistribution.

The patient also has evidence of hirsutism.

Courtesy, Judit Stenn, MD.

Cushing syndrome with multiple striae.

Courtesy, Judit Stenn, MD.

Diffuse hyperpigmentation of Addison disease.

The hyperpigmentation (shown in contrast to the physician’s hand) is accentuated in sun-exposed skin and can also involve sites of trauma, skin creases, and mucosae.

Cutaneous Gastroenterology

With the exception of Table 26.13 , cutaneous aspects of gastroenterologic or hepatic disease are not specifically discussed elsewhere in this text . Table 53.8 is a list of selected cutaneous associations of Crohn disease and ulcerative colitis ( Figs 53.26–53.28 ). Patients with ostomies, particularly those with an ileostomy, may develop peristomal dermatoses, the most common of which are listed in Table 53.9 . Table 53.10 lists dermatologic conditions associated with gastrointestinal bleeding or hemorrhage ( Figs 53.29–53.32 ) .

Pyoderma gangrenosum in a patient with ulcerative colitis and relapsing polychondritis.

Central ulceration preceded by a violaceous bulla with an inflammatory border.

Courtesy, Frank Samarin, MD.

Peristomal pyoderma gangrenosum in the setting of inflammatory bowel disease.

Patients with ostomies, particularly ileostomies, are at risk for peristomal dermatoses, including pyoderma gangrenosum.

“Metastatic” Crohn disease.

Non-contiguous granulomatous inflammation of the skin is often manifested by deep inflammatory fissures in the inguinal folds. These have been described as “knife-like” fissures.

Hereditary hemorrhagic telangiectasia.

Several small red macules and papules on the lips.

Courtesy, Irwin Braverman, MD.

Blue rubber bleb nevus syndrome.

Several venous malformations are evident on this patient’s tongue.

Peutz–Jeghers syndrome.

Multiple brown macules on the vermilion lips and a few on the lower cutaneous lip.

Gingival cobblestoning in Cowden disease.

This patient also had trichilemmomas and a “Cowden nodule” or sclerotic fibroma on the neck.

Table 53.11 lists selected dermatologic aspects of liver disease . Necrolytic acral erythema is an interesting disease that has been described in association with hepatitis C viral infection. This entity is histologically similar to necrolytic migratory erythema (see above), but is clinically distinct in that it primarily involves acral sites. The lesions present as painful or pruritic, pink to violet–brown plaques with hyperkeratosis ( Fig. 53.33 ). Blisters and erosions are common, and disease activity tends to wax and wane. Most reported cases have been associated with hepatitis C viral infection, and there has been variable success following treatment with oral zinc supplementation and/or treatment of the underlying hepatitis C viral infection.

Necrolytic acral erythema.

This is a manifestation of hepatitis C viral infection.

Other Systemic Diseases With Cutaneous Manifestations

Sarcoidosis is an example of a multisystem disease with a range of cutaneous manifestations (see Ch. 93 ) . Table 53.12 reviews the cardiac and dermatologic features of multisystem disorders ( Figs 53.34 & 53.35 ) . Skin changes associated with pulmonary and renal disorders are summarized in Tables 53.13 and 53.14 , respectively ( Figs 53.36–53.38 ) .

Table 53.12

Cardiocutaneous abnormalities in multisystem disorders.

AI-CTD, autoimmune connective tissue disease; CNS, central nervous system; ECG, electrocardiogram; GI, gastrointestinal; EFEMP2, epidermal growth factor (EGF)-containing fibulin-like extracellular matrix protein 2; IVIg, intravenous immunoglobulin; LAMB, lentigines, atrial myxoma, mucocutaneous myxoma, blue nevi; LE, lupus erythematosus; NAME, nevi, atrial myxoma, myxoma of the skin, ephelides; TGF, transforming growth factor.

Adapted from Jorizzo JL, Callen JP. Dermatologic manifestations of internal disease. In: Arndt KA, Robinson JK, LeBoit PE, et al (eds). Cutaneous Medicine and Surgery, Philadelphia: WB Saunders, 1996:1863–89.

CARDIOCUTANEOUS ABNORMALITIES IN MULTISYSTEM DISORDERS
Disease	Cutaneous features	Cardiovascular findings	Comments
Genetic
Cardio-facio-cutaneous syndrome	Generalized ichthyosis-like scaling, keratosis pilaris, café-au-lait macules, sparse curly hair, sparse or absent eyebrows and eyelashes	Pulmonic stenosis, atrial septal defects, hypertrophic cardiomyopathy	Autosomal dominant “RASopathy” due to mutations in four genes that encode proteins in the RAS/MAPK (mitogen-activated protein kinase) pathway (see Fig. 55.5 ): BRAF > MAP2K1, MAP2K2 > KRAS. Patients have characteristic facies, short stature and developmental delay
Costello syndrome	Lax skin on the hands and feet, deep palmoplantar creases, periorificial papillomas, acanthosis nigricans, curly hair	Pulmonic stenosis, hypertrophic cardiomyopathy, arrhythmias	Autosomal dominant “RASopathy” due to mutations in two genes that encode proteins in the RAS/MAPK pathway: HRAS > KRAS . Patients have mental and growth retardation and an increased risk of rhabdomyosarcoma and bladder carcinoma
Carvajal syndrome	Striate epidermolytic palmoplantar keratoderma, woolly scalp hair	Dilated left ventricular cardiomyopathy	Autosomal recessive disorder due to desmoplakin mutations
Cutis laxa	Lax redundant skin with reduced elasticity	Aortic dilation and rupture, pulmonary artery stenosis, right-sided heart failure	Autosomal dominant (AD) and recessive (AR) forms due to mutations in several genes including those that encode elastin, EFEMP2/fibulin-4, fibulin-5, and V-type H + ATPase subunit (see Table 95.5 ); systemic involvement is more common in the AR form
Ehlers–Danlos syndrome (EDS)	Variable degree of skin hyperelasticity and fragility (e.g. “cigarette” paper scars, ecchymoses)	Classic and hypermobility types (I–III): aortic root dilation, mitral and tricuspid valve regurgitation or prolapse	Due to mutations in the genes encoding collagen V (classic type), tenascin X (subset of classic and hypermobility types), collagen III (vascular type), and collagen I (cardiac valvular type)
		Vascular type: arterial aneurysms, dissection and rupture
		Cardiac valvular type: valvular abnormalities
Fabry disease	Angiokeratoma corporis diffusum, hypohidrosis	Hypertrophic cardiomyopathy, valvular abnormalities, conduction defects, progressive atherosclerotic disease of the coronary and cerebral arteries	α-Galactosidase A deficiency, X-linked recessive disorder. Cardiac and cerebrovascular disease and renal failure are the usual causes of death
Hemochromatosis	Generalized bronze hyperpigmentation	Congestive heart failure, supraventricular arrhythmias	Diabetes, cirrhosis. Genetic testing is available for HFE gene mutations
Homocystinuria	Livedo reticularis, malar rash, tissue-paper scars, diffuse pigmentary dilution	Atherosclerosis, arterial and venous thrombosis	Autosomal recessive disorder most commonly due to homozygous cystathionine β-synthase (CBS) deficiency. Rarely due to deficiency of methylenetetrahydrofolate reductase (MTHFR) or other enzymes listed in Table 97.1 . Patients also exhibit marfanoid characteristics and ectopia lentis. Hyperhomocysteinemia (due to homozygous MTHFR deficiency ≫ heterozygous CBS deficiency) also increases risk of arterial and venous thrombosis
LEOPARD syndrome/Noonan syndrome with multiple lentigines	Multiple lentigines, café-au-lait and café-noir macules	ECG abnormalities, pulmonary artery stenosis	L – lentigines, E – ECG abnormality, O – ocular hypertelorism, P – pulmonary stenosis, A – abnormalities of the genitalia, R – retardation of growth, D – deafness.
			Autosomal dominant “RASopathy” due to mutations in PTPN11 (see Fig. 55.5 )
Loeys–Dietz syndrome (types I and II)	Translucent skin, easy bruising, atrophic scarring	Aortic aneurysms, arterial tortuosity; significant risk of aortic dissection and rupture, even at an early age	Autosomal dominant disorder due to mutations in the genes that encode TGF-β receptor 1 and 2. Overlapping clinical features with Marfan syndrome and vascular type EDS. Craniofacial anomalies are seen primarily in type I
Marfan syndrome	Striae, decreased subcutaneous fat	Dilation and dissection of the ascending aorta, mitral valve prolapse and regurgitation	Autosomal dominant disorder due to mutations in the gene that encodes fibrillin-1. Characterized by tall stature with long limbs, arachnodactyly, dolichocephaly, myopia and ectopia lentis. In addition to β-blockers, angiotensin II receptor blockers (e.g. losartan), which antagonize TGF-β signaling, can prevent aortic root dilation
Multiple endocrine neoplasia (MEN) types 2A (Sipple syndrome) and 2B (multiple mucosal neuroma syndrome)	MEN 2A – notalgia paresthetica, macular or lichen amyloidosis, often with childhood onset	Hypertensive crises due to pheochromocytomas (often bilateral)	Autosomal dominant conditions due to mutations in the RET proto-oncogene. Also manifest with medullary cell carcinoma of the thyroid (MEN 2A and 2B), parathyroid adenomas (MEN 2A), and a marfanoid habitus (MEN 2B)
	MEN 2B – neuromas of the eyelids, lips, tongue and other mucosal sites
Carney complex (NAME and LAMB syndromes)	Cutaneous myxomas, blue nevi, lentigines, café-au-lait and café-noir macules	Atrial myxoma	Endocrine neoplasia of the adrenal glands, pituitary gland, and/or testes. Autosomal dominant disorder due to mutations in PRKAR1A ; 2 nd genetic locus on chromosome 2
Naxos disease	Diffuse non-epidermolytic palmoplantar keratoderma, woolly scalp hair	Arrhythmogenic right ventricular cardiomyopathy	Autosomal recessive condition due to mutations in the gene that encodes plakoglobin; same clinical findings rarely caused by desmocollin 2 mutations
Neurofibromatosis 1	Café-au-lait macules, neurofibromas, intertriginous freckling (lentigines)	Hypertension, essential or due to pheochromocytoma or renal artery stenosis	Due to mutations in NF1 , which encodes neurofibromin; the latter interacts with the RAS/MAPK pathway (see Fig. 55.5 )
Hutchinson-Gilford progeria syndrome	Sclerodermoid changes, mottled hyperpigmentation, loss of subcutaneous fat, alopecia	Premature atherosclerosis	Autosomal dominant premature aging syndrome due to mutations in the gene encoding lamins A and C
Pseudoxanthoma elasticum	Yellow papules and plaques on neck and in intertriginous areas, redundant lax skin	Premature atherosclerotic vascular disease, aortic aneurysm, hypertension	Upper or lower GI hemorrhage, angioid streaks in the eye, uterine hemorrhage. Autosomal recessive disorder due to mutations in ABCC6
Tuberous sclerosis complex (TSC)	Facial angiofibromas, periungual and ungual fibromas, ash leaf macules, shagreen patch	Cardiac rhabdomyomas, arrhythmias	Renal angiomyolipomas, CNS tumors, mental retardation, seizures. Due to mutations in TSC1 or TSC2 , which encode hamartin and tuberin, respectively
Werner syndrome	Premature graying, alopecia, sclerodermoid changes, loss of subcutaneous fat, ankle ulcerations	Premature atherosclerosis	Myocardial infarction is usually responsible for death by the fifth decade. Autosomal recessive disorder due to mutations in RECQL2 , which encodes a helicase. Other features include cataracts and malignancy
Inflammatory/autoimmune
Behçet disease	Oral and genital aphthae, pathergy, pustular vasculitis, pyoderma gangrenosum-like lesions, erythema nodosum-like lesions	Pericarditis, coronary arteritis, myocarditis, arrhythmias, valvular disease; vasculitis of the vasa vasorum, primarily of large blood vessels	Ocular and CNS involvement. Inflammatory bowel disease should be excluded
Dermatomyositis	Gottron papules, heliotrope rash, photodistributed poikiloderma	Usually asymptomatic; arrhythmias, conduction defects; pericarditis and congestive heart failure are rare	Cardiac involvement is a poor prognostic sign
DRESS/DIHS (drug hypersensitivity with eosinophilia and systemic symptoms/ drug-induced hypersensitivity syndrome)	Widespread morbilliform or urticarial eruption or erythroderma; facial edema often present	ECG changes may simulate acute myocardial infarction; acute myocardial dysfunction and hypotension which may initially appear during taper of corticosteroids	Fever, hepatitis, and peripheral eosinophilia common (see Table 21.9 ). Treatment consists of discontinuation of offending drug and corticosteroids; can follow levels of N-terminal pro-brain natriuretic peptide (NT-proBNP). Long-term consequences include thyroid dysfunction and possible autoimmune disease
Kawasaki disease (mucocutaneous lymph node syndrome)	Glossitis, cheilitis, acral erythema, edema and desquamation, polymorphous eruption, conjunctival injection	Coronary arteritis, coronary artery aneurysms	High fever, lymphadenopathy. Treatment with IVIg and aspirin significantly decreases risk of coronary artery disease
Neonatal lupus erythematosus (NLE)	Transient, non-scarring annular lesions of LE (SCLE-like) that favor the periorbital region	Congenital heart block (CHB)	Presumed to be due to transplacental passage of autoantibodies, most commonly anti-SSA/Ro, but anti-RNP also detected. May have transient cytopenias and hepatitis. Mothers often have a known AI-CTD (~50%) and in those without a known AI-CTD, a significant percentage will develop one over time. For mothers with anti-SSA/Ro antibodies, there is <1% chance of having a baby with NLE, but once have baby with NLE, chance in subsequent pregnancies is 25%
Systemic lupus erythematosus	Malar erythema, photosensitivity, lupus skin lesions. Patients with antiphospholipid antibodies may have necrotizing livedo reticularis, leg ulcers or widespread cutaneous necrosis ( Fig. 53.34 )	Pericarditis, verrucous endocarditis (Libman–Sacks), coronary artery disease	Anti-cardiolipin antibody may play a role. Treatment of LE with corticosteroids may predispose to coronary artery disease
Multicentric reticulohistiocytosis	Erythematous nodules of the hands and, less often, the extremities and the face ( Fig. 53.11 )	Pericarditis, congestive heart failure, coronary artery disease, cardiomegaly	Deforming arthritis is frequent
Psoriasis	Well-demarcated, pink-to-red plaques with silvery scale on the elbows, knees and scalp, around the umbilicus, and in the gluteal cleft	Increased risk of cardiovascular disease, including cerebrovascular and peripheral artery disease. In patients with moderate to severe psoriasis, possible increased risk of death from atherosclerotic cardiovascular disease	High incidence of metabolic syndrome in patients with moderate to severe psoriasis (see Table 53.5 )
Relapsing polychondritis	Beefy, red ears (sparing the lobes); inflammation in other tissues with cartilage (e.g. the nose). Late findings include floppy ears and weakness in other areas where the cartilage was affected ( Fig. 53.35 )	Aortic insufficiency, dissecting aortic aneurysm	Arthritis, tracheal collapse. Dapsone may be helpful. Corticosteroids and/or other immunosuppressive agents are also used
Rheumatic fever	Erythema marginatum, subcutaneous nodules	Pancarditis in the acute phase. Late manifestations include mitral and/or aortic valve dysfunction	Rare in US. Follows pharyngitis due to group A β-hemolytic streptococcal infection. Polyarthritis, chorea, fever
Sarcoidosis	Papules, nodules, plaques and/or lesions in scars ( Fig. 53.36 )	Conduction defects, congestive heart failure	Pulmonary disease, lymphadenopathy, hepatic involvement, hypercalcemia. Cardiac involvement denotes a poor prognosis
Systemic sclerosis (scleroderma)	Cutaneous sclerosis, Raynaud phenomenon	Pulmonary artery hypertension, conduction defects, pericarditis, visceral Raynaud phenomenon	Cardiac involvement denotes a poor prognosis. May also have interstitial lung disease
Vasculitis	Palpable purpura, nodules, livedo reticularis, ulcerations	Coronary artery vasculitis	Arthritis, GI colic or bleeding. Cardiac involvement is uncommon
Neoplastic
Primary systemic amyloidosis (AL)	Pinch purpura, waxy skin, translucent papules, macroglossia	Restrictive cardiomyopathy, conduction disturbances	Proteinuria, urinary light chains, association with plasma cell dyscrasia ≫ multiple myeloma
Carcinoid syndrome	Flushing; pellagra-like dermatitis and sclerodermoid features may occur as late manifestations	Endocardial plaques – tricuspid insufficiency, conduction defects	Flushing associated with ~10% of mid-gut tumors (small intestine, appendix, proximal colon) and liver metastases are required; type III gastric and bronchial carcinoid tumors are also associated with flushing (liver metastases are not required)
Infectious
Endocarditis – bacterial or fungal	Purpura, nail-fold infarction, Janeway lesions, Osler’s nodes	Vegetations and dysfunction of the valves	Fever. May simulate vasculitis or cryoglobulinemia
Metabolic/endocrine
Diabetes mellitus	See Table 53.4	Coronary artery and peripheral artery disease	Occurs with both type 1 and type 2; insulin resistance may contribute
Hyperlipidemia	Xanthomas of multiple types	Coronary artery disease	See Ch. 92
Other
Exfoliative erythroderma	Exfoliative dermatitis	High-output cardiac failure	The eruption may be due to dermatitis, psoriasis, cutaneous T-cell lymphoma, a drug eruption or other causes
PHACE(S) syndrome	Segmental infantile hemangioma, most often of the face and neck	Coarctation of the aorta, atrial and ventricular septal defects, anomalous cervical and cerebral arteries	P – posterior fossa malformations, H – hemangioma, A – arterial anomalies, C – cardiac defects and coarctation of the aorta, E – eye anomalies, S – sternal defects and supraumbilical raphe

Only gold members can continue reading. Log In or Register to continue

Share this:

• Click to share on Twitter (Opens in new window)
• Click to share on Facebook (Opens in new window)

Related

Related posts:

Molecular Biology Cutaneous Vasculitis Morphea and Lichen Sclerosus Histiocytoses Smooth Muscle, Adipose and Cartilage Neoplasms Chemical and Mechanical Skin Resurfacing

Stay updated, free articles. Join our Telegram channel

Join