cutaneous manifestations of systemic disease · • tripe palms: (lung ca); tripe palms + an: ......

Cutaneous Manifestations

of Systemic DiseaseBeaumont Health – Botsford Hospital

Dermatology

Alexander Dane DO, Ivy DeRosa DO, Megan Furniss DO,

Summer Moon DO, Bryan Gray DO, Nichelle Arnold DO

Program Director: Annette LaCasse, DO

• Acrodermatitis enteropathicaAcrodyniaAcute febrile neutrophilic dermatosisAmyloidosisAngioedemaAnnular erythemaAntiphospholipid syndromeArgyriaAutoinflammatory syndromesBehçet diseaseBiotin-responsive dermatosesBlau syndromeBloom syndromeBowel bypass syndromeCalciphylaxisCarotenaemiaChilblainsChloracneChurg Strauss syndromeCINCACompulsive skin pickingCongenital adrenal hyperplasiaCongenital erythropoeitic porphyriaConnective tissue diseasesCostello syndromeCrohn diseaseCryoglobulinaemiaCushing syndromeCutaneous markers of malignancyCryopyrin-associated periodic syndromesDegos diseaseDermatitis herpetiformisDermatomyositisDiabetesDiabetic foot ulcersDown syndromeDrug eruptionsDysmorphophobiaEhler Danlos syndromeEosinophilic fasciitisErythema multiformeErythema nodosumErythropoeitic protoporphyriaFamilial cold autoinflammatory syndromeFamilial Mediterranean fever

• FlushingFocal dermal hypoplasiaGenital Crohn diseaseGlucagonomaGoltz syndromeGorlin syndromeGoutGraft versus host disease

• Livedo reticularisLupus erythematosusLyme diseaseMajeed syndromeMarfan syndromeMastocytosisMcCune-Albright syndromeMenopauseMetabolic syndromeMevalonic aciduriaMonogenic autoinflammatory syndromesMorphoeaMucinosesMuckle-Wells syndromeMyxoma syndromeNecrobiosis lipoidicaNecrolytic migratory erythemaNeurotic excoriationsNOMIDOrofacial Crohn diseaseOrofacialdigital syndrome type 1Orofacial manifestations of inflammatory bowel diseasePanniculitisPAPA syndromePeriodic fever syndromesPFAPA syndrome

• PhotosensitivityPOEMS syndromePolyarteritis nodosaPolymorphous eruption of pregnancyPorphyria cutanea tardaPretibial myxoedemaProlidase deficiencyPrurigo nodularisProteus syndromePruritusPseudoxanthoma elasticumPyoderma gangrenosumPyodermatitis-Pyostomatitis vegetansReiter syndromeReticular erythematous mucinosisRheumatoid arthritisRothmund-Thomson syndromeSAPHO syndromeSarcoidosisSchnitzler syndromeScleroderma (localised)ScleredemaScleromyxoedemaScurvySézary syndromeSjögren syndromeSkin cancer in transplant recipients

• Variegate porphyriaVasculitisWaldenström macroglobulinaemaWegener granulomatosisWells syndromeWhipple diseaseWilson diseaseXanthomasXeroderma pigmentosum

Wow! That’s

sure a lot of

diseases!

B. Gray

Cutaneous Manifestations of Systemic Disease

• Internal Malignancies • Cardiovascular• Pulmonary• Rheumatic• Gastrointestinal• Renal• Metabolic/Endocrine

Internal Malignancies

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Metastatic Carcinoma• Direct extensions or distant metastasis via lymphatic or

hematogenous dissemination

• The most frequent primary tumors are carcinomas of the breasts, stomach, lungs, uterus, kidneys, ovaries, colon, or bladder.

• Approximately 1.0% to 4.5% of internal cancers metastasize to the skin.

• Metastases from the breast, lung, and genitourinary system have a propensity for the scalp

• GI tract cancers often manifest on the skin of the abdominal wall.

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Acanthosis Nigricans• Acanthosis nigricans has various subtypes relating to cause and/or

location: obesity-associated, syndromic, acral, unilateral, familial, drug-induced, and malignant.

• Three common types: AN with maligancy, familial, insulin-resistant states/syndromes

• Assoc. conditions include: obesity, diabetes, polycystic ovarian syndrome (PCOS), Cushing syndrome, HAIR-AN, Atypical (palmar or mucosal) distributions or acute onset acanthosis nigricans may also be associated with malignancy (usually gastrointestinal adenocarcinoma).

• Tripe palms: (Lung CA); Tripe palms + AN: (Gastric CA)

• Associated drugs: Niacin, insulin, folate, estrogens, protease inhibitors

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Extramammary Paget’s (EMPD)• Approximately a quarter of cases are associated with an underlying neoplasm,

usually adnexal apocrine carcinoma, but cases of carcinoma of the prostate, urethra, cervix, vagina, endometrium, bladder, and Bartholin's glands have been described.

• Perianal disease is more frequently associated with an underlying carcinoma of the rectum.

• In vulvar EMPD 4–17% have an associated adnexal neoplasm, and some have a distant carcinoma of the breast, cervix, vagina, bladder, colon, rectum, ovary, liver, gallbladder, or skin.

• In perianal EMPD an underlying adnexal carcinoma occurs in 7–10% of cases, and a distant carcinoma of the rectum, stomach, breast, or ureter in 15–45%.

• In penile/scrotal EMPD has an associated carcinoma of the prostate, bladder, testicles, ureter, or kidney in 11% of cases.

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Primary Systemic Amyloidosis (PSA)

• Multiple myeloma is the most common association, but it is also seen with Waldenstrom macroglobulinemia and other paraproteinemias.

• Neurologic symptoms include a sensory peripheral neuropathy, presenting in a stocking and glove distribution. An "idiopathic" carpal tunnel syndrome can also occur.

• Cardiac arrhythmias and right sided congestive heart failure are common causes of death

• The diagnosis is confirmed by evaluation of the patient’s serum and urine for immunoglobulin fragments and by amyloid stains or electron microscopy of the skin biopsies

Cardiovascular

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Leopard Syndrome• Multiple Lentigines, Electrocardiographic conduction

abnormalities, Ocular hypertelorism, Pulmonary stenosis, Abnormalities of genitalia, Retardation of growth, sensorineural Deafness

• AD; PTPN11 gene mutation leads to abnormal RAS/MAPK activation

• Most common cardiac abnormality is hypertrophic cardiomyopathy– Important to identify early as HOCM is most common cause of

sudden cardiac death in young persons

8/21/2015 VisualDx - Image Zoom - Child Rash: Carney Complex

http://www.visualdx.com/visualdx/visualdx6/getZoomImage.do?moduleId=10&diagnosisId=50724&imageIndex=1 1/1

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Carney Complex• Multiple neoplasia syndrome including skin findings (lentigines,

blue nevi, café-au-lait spots, cutaneous fibromas/myxomas), endocrine overactivity/tumors (primary pigmented nodular adrenal hyperplasia), and visceral myxomas (cardiac)

• AD; PRKAR1A gene causes dysfunction of regulatory subunit of Protein Kinase A

• 80% of patients with atrial myxoma will present with co-existant or preceding cutaneous myxoma

• Early echocardiogram recommended to detect valvular obstruction and prevent stroke

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Pseudoxanthoma Elasticum

• Hereditary disorder marked by abnormal calcification of elastic fibers. Findings include “plucked chicken” skin at flexural sites, retinal (angioid streaks), GI (gastric artery aneurysm), and CV (HTN, accelerated CAD, MVP) manifestations.

• AR; mutation in ABCC6 gene

• Typically skin changes precede all others

• Important to control/eliminate cardiac risk factors

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Marfan’s Syndrome

• AD: Caused by mutation in fibrillin-1, a component of extracellular matrices causing characteristic body habitus, hyperextensible joints, skeletal abnormalities, upward lens dislocation, and aortic aneurysm

• Skin findings include distensible skin, striae densa, and elastosis perforans serpiginosa

• Most commonly affected with MVP and aortic root dilation: at risk for AR, dissection, and rupture.

Pulmonary

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Sarcoidosis• Multi-organ granulomatous disease attributed to

overactivity of cell mediated immunity• Eitiology proposed to be autoimmune, environmental

vs infectious• Up to 1/3 of patients with systemic sarcoid will have

skin lesions; typical lesions are red to brown papules and plaques on lips, nose, neck, upper trunk and extremities.

• 90% of patients WILL have lung involvement.

Sarcoidosis• Aveolitis and

granulomatous infiltration of vessels, bronchioles.

• Hilar lymphadenopathy is commonly present though often asymptomatic

• End stage results in honeycombing fibrosis

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Sarcoidosis• Diagnosis is made with clinical and histological

findings• Chest X-ray recommended to allow for baseline

and follow up• High resolution CT scans differentiate fibrosis

from inflammation• Pulmonary function tests are helpful if patient

becomes symptomatic

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Yellow Nail Syndrome• Pathogensis unknown, rare

• Triad includes lymphedema, nail changes and respiratory tract involvement

• Nails become hyperkeratotic, color from pale to dark yellow to green

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Yellow Nail Syndrome• Condition is associated

with chronic bronchitis, pleural effusions, bronchiectasis, sinusitis

• Often involves all 20 nails

• Lunulae may be absent, inc longitudinal and transverse curvature

• Any patient you suspect needs Chest Xray and ENT eval

• TX: Treat the underlying disease! (Also Vit E and antifungals are helpful)

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Erythema Gyratum Repens

• Figurate erythema with “Rings with in rings” pattern

• Migrates up to a 1 cm/day

• Lesions are typically itchy and scaly

• Possible cross reactivity between tumor and cutaneous antigens

Erythema Gyratum Repens• **Paraneoplastic**

• Most commonly associated with lung cancer

• May occur 1 year before or following diagnosis.

• Thorough workup with chest Xray/CT scans are warranted!

• Tx underlying neoplasm1

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Acrokeratosis Paraneoplastica• ‘Bazex Syndrome’

• Nails most commonly present first. Brittle, hyper-keratotic and deform nail plate.

• Also noted are erythematous papules and plaques on acral areas, nose or helices of ears

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• **Paraneoplastic** phenomenon most commonly for upper aerodigestive tract cancers, commonly squamous cell cancer.

• Detailed workup for neoplasms in larynx, pharynx and esophagus.

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Rheumatic

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Psoriatic Arthritis• Psoriatic Arthritis occurs in 5-30% of patients with

cutaneous psoriasis.• In 10-15% of patients symptoms of psoriatic arthritis

appear before skin involvement. • Risk Factors include early age of onset, female,

polyarticular involvement, genetic predisposition, and radiographic signs of disease early on.

• Most commonly patients present with rheumatoid factor negative, mono- and asymmetric oligoarthritis• Affecting the small joints of the hands

Psoriatic Arthritis

• Onycholysis is more frequently associated with psoriatic disease.

• Associated with obesity, T2DM, HTN, dyslipidemia, non-alcoholic steatohepatitis, CVD and lymphoma• CRP is a predictor of CVD as well as joint inflammation.

• HLA-B27 associated spondylitis and sacroilitis may have associated IBD and/or uveitis.

• Early diagnosis of psoriatic arthritis is important, as disease progression may result in loss of dextertity.

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Dermatomyositis• Diagnose with triceps muscle biopsy, EMG, MRI or U/S. • Internal disease associations include:

– Interstitial fibrosis occurs in 15-30% of patients and is associated with Anti-aminoacyl-tRNA synthetaseantibodies. • Amyopathic DM with rapidly progressive interstitial

lung disease is associated with Anti-CADM-140 antibodies. Cancer assoc. anti-155kDa

– Cardiac disease presents with arrhythmia or conductiondefects and is associated with Anti-SRP antibodies

Dermatomyositis• Risk of malignancy varies from 10-50% and is highest

within the first few years of disease.– Occurs most commonly in the adult and amyopathic subtypes.– Anti-155/140 antibodies are associated with internal malignancy

risk.– Lung and GI cancer are more common in men.– Ovarian and breast cancer are more common in women

• Recommendations: Evaluate for malignancy (chest/abdomen/pelvis CT) at baseline and at regular intervals for 2-3 yrs post diagnosis.

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Systemic Lupus Erythematosus

• Serositis (Pleuritis, Pericarditis)

• Oral Ulcers• ANA • Photosensitivity• Blood (Hemolytic anemia,

leukopenia, lymphoma, thrombocytopenia)

• Renal (Proteinuria or cellular casts)

• Arthritis (non-erosisve)

• Immunology abnormality ((anti-dsDNA, anti-sm, antiphopholipid)

• Neurological disorder (seizures or psychosis)

• Malar Rash

• Discoid lesions.

Need 4/11 for diagnosis

Systemic Lupus Erythematosus

• Associations: HLA-DR2, HLA-DR3

• Labs: ANA with profile (anti-dsDNA, anti-sm), urinalysis, CBC with diff, platelet count, CMP, ESR, C3, C4.

• Must exclude drug induced systemic lupus erythematosis

– Usually lacks renal disease or CNS symptoms

– Hydralazine, procainamide, chlorpromazine, INH, quinidine, practolol, d-penicillamine, PUVA, minocycline

Gastrointestinal

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Dermatitis Herpetiformis, a.k.a. Duhrings Disease

• Strongly associated with celiac disease, > 90% of those with DH have CD

• HLA-DQ2 > HLA-DQ8 • Test of serum IgA anti-tissue transglutaminase-2 and anti-gliadin

antibodies, total serum IgA• Small bowel biopsy is gold diagnostic standard, reveals blunting of

the papillae • Direct Immunoflorescence reveals granular IgA in the dermal

papillae• Increased risk of developing Hashimoto's thyroiditis, non-

Hodgkin's lymphomaand GI lymphomas.

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Acrodermatitis Enteropathica• Congenital zinc deficiency• SLC39A4 zinc uptake protein defect• Erosive, recalcitrant, seborrheic dermatitis-like

rash in a periorificial, acral and diaper region, as well as alopecia and diarrhea

• Labs: serum zinc and alkaline phosphatase • Acquired form has similar presentation, which is

often precipitated by weaning

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Necrolytic Migratory Erythema • **Paraneoplastic**

• Affects skin around the mouth and extremities; but may also be found on the lower abdomen, buttocks, perineum, and groin

• Strongly associated with glucagonoma – syndrome includes: NME, weight loss, glossitis, and DM

• Other assoc: liver disease and intestinal malabsorption

• Work-up: glucagon levels, serum glucose, chromogranin A, LFTs, CBC

• Imaging: CT/MRI/US abdomen and PET scan as indicated by labs and symptoms

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Lichen Planus

• May be the presenting sign of Hepatitis C infection – Erosive mucosal LP is MC in HCV

• Typically more difficult to treat than non-mucosal LP

• Associated with HBV immunization, primary biliary cirrhosis, medications and dental amalgams

• Oncogenic role of HCV driving oral LP SCC debated, evidence is country specific

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Muir-Torre Syndrome • AD: DNA mismatch repair gene defect in MSH2, (MC)

MLH1, also MLH3, PMS2, or MSH6.• Characterized by sebaceous adenomas, epitheliomas, and

carcinomas as well as keratoacanthomas• Strongly associated with GI carcinoma• Also associated with GU, breast, hematologic, and head &

neck malignancies• Sebaceous tumors can present prior to, concurrently with,

or after the diagnosis of a visceral malignancy• Negative stains for MSH2 and/or MLH1 on histopathology• Current recommendation for colonoscopy q1-2 years,

monitor 1st degree relatives

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Peutz-Jeghers a.k.a. Hereditary Intestinal Polyposis Syndrome

• AD, STK 11 gene GI polyposis and GI adenocarcinoma

• Characterized by mucocutaneous lentigines with perioral, oral mucosal and acral distribution

• Screening for internal malignancy based on FHx

• Annual CBC, hemoccult, CA-125 (starting at 18yo) and CA-19-9 (starting at 25)

• Begin mammography in 3rd decade

• Other associated malignancies include ovarian, cervical, testicular, breast, and pancreatic

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Pyoderma Gangrenosum

• Inflammatory bowel disease: (MC)• Ulcerative colitis• Crohn's Disease

• Arthritides:• Rheumatoid arthritis• Seronegative arthritis

• Hematological disease:• Myelocytic leukemia• Hairy cell leukemia• Myelofibrosis• Myeloid metaplasia• Monoclonal gammopathy

• Autoinflammatory Disease:• Pyogenic sterile arthritis, pyoderma

gangrenosum, and acne syndrome (PAPA syndrome)

• Other Autoimmune Disease:• SLE• Sjogren’s Syndrome • Primary Biliary Cirrhosis

• Physiologic stress such as surgery

• Treatment may require systemic immunosuppression

Renal

CD 34+1

Nephrogenic Systemic Fibrosis • Renal injury and exposure to a gadolinium based

contrast agent activation of circulating fibrocytesand creation of a highly active immune state

• Sleroderma-like skin changes including patterned erythematous plaques, “cobblestoning,” joint contractures, and marked induration/Peaud’orange

• Histopath demonstrates thickened collagen bundles, “tram track” arrangement, CD34+

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Birt-Hogg-Dubé Syndrome

• AD, BHD gene encoding folliculin on 17p11.

• Growth of fibrofolliculomas, (acrochordons/trichodiscomas) and susceptibility to malignant renal tumors (chromophobe) as well as lung disease

• Recurrent spontaneous pneumothoraces, bullous emphysema, lung cysts

• Chest x-ray and abdominal CT, screening of first degree relatives.

Metabolic/Endocrine

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Porphyria Cutanea Tarda • 75%-PCT-S, (sporadic variant) linked to liver disease• Hepatic associations include: Hep C, alcoholic liver disease, and

hemochromatosis• Hepatic impairment of uroprphyrinogen decarboxylase (UROD) photoreactive porphyrins• Porphyrins absorb at 400 – 410nm (Soret band)

• Associated with DM, HIV, estrogen therapy, and exposure to polyhalogenated hydrocarbons, and hemodialysis

• Dx: 24 hour urine for porphyrins and fecal studies– Ratio of Uroporphyrin:coproporphyrin is 3:1-5:1– Isocoproporphyrin in feces (pathognomonic)

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Diabetic Dermopathy

• risk of neuropathy, retinopathy and nephropathy.

• 53% of patients also have CAD

• Presents with multiple (> 4), well demarcated, atrophic, depressed, hyperpigmented macules on the shin of a patient with diabetes

• Must attempt to establish a diagnosis of diabetes or evaluate for complications of pre-existing illness

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Calciphylaxis • 1-4% of dialysis patients annually • Mortality rate up to 80% • Risk factors include: female sex, ESRD, hypophosphatemia,

secondary hyperparathyroidism, hypercalcemia, calcium-based phosphate binders, obesity, diabetes, protein C and S deficiency, warfarin, liver disease, and systemic steroid use.

• Diagnosed by full thickness biopsy adjacent to necrosis • Multidisciplinary approach: nephrology, endocrinology,

dermatology, wound care, pain management, and nutrition.

Overview• Internal Malignancies (cutaneous metastases, Paget’s Dz., acanthosis nigricans, amyloidosis,

paraneoplastic pemphigus, tripe palms)

• Cardiovascular disease (LEOPARD syndrome, Carney complex, PXE, Ehlers Danlos)

• Pulmonary disease (Sarcoidosis, Bazex Sign (acrokeratosis neoplastica), erythema gyratumrepens, Yellow Nail Syndrome)

• Rheumatic disease (Psoriatic Arthritis, Lupus erythematosus, dermatomysositis)

• Gastrointestinal disease (DH, acrodermatitis enteropathica, necrolytic migratory erythema, Lichen planus, Muir-Torre, Peutz-Jeghers, pyoderma gangrenosum)

• Renal (NSF, Birt-Hogg-Dube)

• Metabolic/Endocrine (Porphyrias, Diabetic dermopathy, calcichylaxis)

Thank you!

References• Metastatic Carcinoma

Alcaraz I, Cerroni L, Rütten A, Kutzner H, Requena L. Cutaneous metastases from internal malignancies: a clinicopathologic and immunohistochemical review. Am J Dermatopathol. 2012 Jun;34(4):347-93(1), (2) http://www.visualdx.com/visualdx/visualdx6/getDiagnosisText.do? moduleId=11&diagnosisId=51257(3), (4) Dane, A. Medical Mission, Iquitos, Peru. 2013

• Acanthosis NigricansBraverman IM. Skin manifestations of internal malignancy. Clin Geriatr Med. 2002 Feb;18(1):1-19(1), (2), (3) http://www.visualdx.com/visualdx/visualdx6/getDiagnosisText.do? moduleId=7&diagnosisId=51010

• Extramammary Paget’s DiseaseMengjun B, Zheng-Qiang W, Tasleem MM. Extramammary Paget's disease of the perianal region: a review of the

literature emphasizing management. Dermatol Surg. 2013 Jan;39(1 Pt 1):69-75Ibrahim SF, Grekin RC, Neuhaus IM. Mammary and extramammary Paget's Disease. In: Goldsmith LA, Katz SI, Gilchrest

BA, Paller AS, Leffell DJ, Wolff K, eds. Fitzpatrick's Dermatology in General Medicine. 8th ed. New York, NY: McGraw-Hill; 2012:1372-1376.

(1), (2) http://www.visualdx.com/visualdx/visualdx6/getDiagnosisText.do?moduleId=7&diagnosisId=52100

• Primary Systemic AmyloidosisLachmann HJ, Hawkins PN. Amyloidosis and the skin. In: Fitzpatrick TB, Wolff K, eds. Fitzpatrick's Dermatology in

General Medicine. 7th ed. New York, NY: McGraw-Hill; 2008:1257-1265Xavier SD, Bussoloti IF, Müller H. Macroglossia secondary to systemic amyloidosis: case report and literature review. Ear

Nose Throat J. 2005 Jun;84(6):358-61.(1), (2) http://www.visualdx.com/visualdx/visualdx6/getDiagnosisText.do?moduleId=7&diagnosisId=52988

• LEOPARD SyndromeSei-Ichiro M, Yoko Y, Sachiko O, et al. Pathogenesis of Multiple Lentigines in LEOPARD syndrome with PTPN11 Gene Mutation. ActaDerm Venerol. 2015Tidyman WE, Rauen KA. Noonan, Costello and cardio-facio-cutaneous syndromes: dysregulation of the Ras-MAPK pathway. Expert Rev Mol Med 2008; 10: e37.(1) http://www.scielo.br/scielo.php?pid=S0365-05962006000600014&script=sci_arttext&tlng=en(2) http://www.bsecho.org/hypertropic-cardiomyopathy/

• Carney SyndromeKaltsas G, Kanakis G, Chrousos G. Carney’s Complex. [Updated 2013 Jul 31]. In: De Groot LJ, Beck-Peccoz P, Chrousos G, et al.,

editors. Endotext [Internet]. South Dartmouth (MA): MDText.com, Inc.; 2000-. Available from: http://www.ncbi.nlm.nih.gov/books/NBK279117/

Espiard S, Bertherat J. Carney complex. Front Horm Res, 2013. 41: p. 50-62.(1) http://www.visualdx.com/visualdx/visualdx6/getZoomImage.do moduleId=10&diagnosisId=50724&imageIndex=1(2) http://emedicine.medscape.com/article/160000-clinical(3) http://ehjcimaging.oxfordjournals.org/content/9/3/430

• Pseudoxanthoma ElasticumLi Y, Cui Y, Zhao H, Wang C, Liu X, Han J. Pseudoxanthoma elasticum: A review of 86 cases in China. Intractable & Rare

Diseases Research. 2014;3(3):75-78. doi:10.5582/irdr.2014.01011.Li Q, Jiang Q, Pfendner E, Váradi A, Uitto J. Pseudoxanthoma elasticum: Clinical phenotypes., molecular genetics and putative

pathomechanisms. Exp Dermatol. 2009; 18:1-11(1) http://www.aocd.org/?page=PseudoxanthomaElast(2) http://www.ohiolionseyeresearch.com/eye-center/glossary/angioid_streaks/

• Marfan’s SyndromeFrydman M. The Marfan syndrome. Isr Med Assoc J. 2008 Mar;10(3):175-8. PubMed ID: 18494226Ammash NM, Sundt TM, Connolly HM. Marfan syndrome-diagnosis and management. Curr Probl Cardiol. 2008 Jan;33(1):7-39.

PubMed ID: 18155514(1) http://escholarship.org/uc/item/5ts1v967(2) http://80.36.73.149/almacen/medicina/oftalmologia/enciclopedias/duane/pages/v1/v1c073.html

• Sarcoidosis

Bolognia, J. Sarcoidosis, Bolognia, 3rd Edition. 2012.

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(3) http://www.gpnotebook.co.uk/simplepage.cfm?ID=93978694

• Yellow Nail Syndrome

Kurin M, Wiesen J, Mehta AC2. Yellow nail syndrome: A case report and review of treatment options. Clin Respir J. 2015 Aug 10. doi: 10.1111/crj.12354.

Lotfollahi L, Abedini A et al. Yellow Nail Syndrome: Report of a Case Successfully Treated with Octreotide. Tanaffos. 2015;14(1):67-71.

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• Erythema Gyratum Repens

Bolognia, J. at al, Erythema Gyratum Repens. Bolognia, 3rd Edition. 2012.

• Acrokeratosis ParaneoplasticaRobert M, Gilabert M, et al. Bazex syndrome revealing a gastric cancer. Case Rep Oncol. 2014 Apr30;7(1):285-7. doi: 10.1159/000362787Rodriguez A jr, Gresta L, et al. Bazex syndrome. An Bras Dermatol. 2013 Nov-Dec;88(6 Suppl 1):209-11. doi: 10.1590/abd1806-4841.20132488.(1) https://expertconsult.inkling.com/read/dermatology-bolognia-jorizzo-schaffer-3rd/chapter-53/figure-53-7(2) http://www.vgrd.org/archive/cases/2008/bazex/bazex.htm(3) http://www.visualdx.com/visualdx/visualdx6/getDiagnosisText.do?moduleId=19&diagnosisId=51170

• Psoriatic ArthritisNestle FO, Kaplan DH, Barker J: Psoriasis. N Engle J Med. 2009;361;496-509. Tobin AM, Veale DJ, Fitxgerald O, et al: Cardiovascular Disease and Risk Factors in Patients with Psoriasis and Psoriatic Arthritis. The journal of Rheumatology 2010;37:7(1)http://www.physio-pedia.com/Psoriatic_Arthritis(2)http://www.medscape.com/viewarticle/750045_5(3)http://www.medicinenet.com/psoriatic_arthritis_pictures_slideshow/article.htm(4)http://www.medicinenet.com/psoriatic_arthritis/article.htm

• DermatomyositisTazelaar HD, Viggiano RW, Pickersgill J, Colby TV: Interstitial lung disease in polymyositis and dermatomyositis. Clinical features and prognosis as correlated with histologic findings. Am Rev Respir Dis. 141:727-733 1990 Askari AD, Huettner TL: Cardiac abnormalities in polymyositis/dermatomyositis. Semin Arthritis Rheum. 12:208-219 1982 Chow WH, Gridley G, Mellemkjaer L, et al.: Cancer risk following polymyositis and dermatomyositis: a nationwide cohort study in Denmark. Cancer Causes Control. 6:9-13 1995 Hill CL, Zhang Y, Sigurgeirsson B, et al.: Frequency of specific cancer types in dermatomyositis and polymyositis: a population-based study. Lancet. 357:96-100 2001. (1) http://images.rheumatology.org/viewphoto.php?imageId=2862868&albumId=75696(2) http://Dermnet.com(3) http://hardinmd.lib.uiowa.edu/dermnet/dermatomyositis6.html(4) http://www.dermrounds.com/photo/dermatomyositis-heliotrope-2/next?context=user

• Systemic Lupus ErythematousCallen JP: Collagen vascular diseases. J Am Acad Dermatol. 51:427-439 2004 Englert HJ, Hawkes CH, Boey ML, et al.: Degos’ disease: association with anticardiolipin antibodies and the lupus anticoagulant. Br Med J (Clin Res Ed). 289:576 1984 Frances C,Piette JC: Cutaneous manifestations of Hughes syndrome occurring in the context of lupus erythematosus. Lupus. 6:139-144 1997(1) www.accessmedicine.com(2) http://www.hss.edu/professional-conditions_in-depth-topic-review-systemic-lupus-erythematosus.asp(3) http://dxline.info/diseases/raynauds-phenomenon(4) http://medicalpicturesinfo.com/discoid-lupus-erythematosus/

• Dermatitis HerpetiformisBolognia J, J Jorizzo, J Shaffer, et al., Dermatology, 3rd edition, Chapter 31(1) http://www.derm101.com/therapeutic/dermatitis-herpetiformis-2/clinical-case/(2) http://www.doctortipster.com/1999-dermatitis-herpetiformis.html(3) http://www.derm101.com/therapeutic/dermatitis-herpetiformis-2/clinical-case/

• Acrodermatitis EnteropathicaBolognia J, J Jorizzo, J Shaffer, et al., Dermatology, 3rd edition, Chapter 51Küry, S; Dréno, B; Bézieau, S; Giraudet, et al. Jp (July 2002). "Identification of SLC39A4, a gene involved in acrodermatitisenteropathica". Nature Genetics 31 (3): 239–40. doi:10.1038/ng913. PMID 12068297.(1) http://www.riversideonline.com/health_reference/articles/dg00023.cfm

• Necrolytic Migratory ErythemaJames W, T Berger, D Elston, Andrews’ Diseases of the Skin: Clinical Dermatology, 11th edition, Chapter 22(1) http://www.medscape.com/viewarticle/487806(2)http://dermnetnz.org/systemic/img/s/glucagon1-s.jpg

• Lichen PlanusNagao Y, Kameyama T, Sata M: Hepatitis C virus RNA detection in orallichen planus tissue [letter]. Am J Gastroenterol. 93:850 1998Carrozzo M1, Scally K1. World J Gastroenterol. Oral manifestations of hepatitis C virus infection.http://www.uptodate.com/contents/lichen-planus(1) http://www.ijdr.in/article.asp?issn=0970-9290;year=2011;volume=22;issue=6;spage=827;epage=834;aulast=Hiremath

• Muir-Torre SyndromeBolognia J, J Jorizzo, J Shaffer, et al., Dermatology, 3rd edition, Chapter 63Curry ML, Eng W, Lund K, et al.: Muir-Torre syndrome: role of the dermatopathologist in diagnosis. Am J Dermatopathol. 26:217-221 2004(1) http://www.eyeplastics.com/sebaceous-cell-carcinoma-malignant-eyelid-lesions-eyelid-tumors-cancer.html(2) https://www.dermquest.com/image-library/image/5044bfcfc97267166cd621f0(3)http://skinpathologyatlas.com/tumors/sebaceousglands/sebaceous-adenoma.htm

• Peutz-Jeghers

Bolognia J, J Jorizzo, J Shaffer, et al., Dermatology, 3rd edition, Chapter 53

https://rarediseases.org/rare-diseases/peutz-jeghers-syndrome

(1) http://www.anatomybox.com/peutz-jeghers-syndrome/

(2) https://www.studyblue.com/notes/note/n/e1-dermatology-pt-ii/deck/3719025

• Pyoderma Grangrenosum

Brooklyn, Trevor; Giles Dunnill; Chris Probert (2006). "Diagnosis and treatment of pyoderma gangrenosum". British Medical Journal 333: 181–184.

http://www.ncbi.nlm.nih.gov/pubmed/26253362

(1) http://www.dermnet.com/images/Pyoderma-Gangrenosum

• Nephrogenic Systemic Fibrosis

Kribben A, Witzke O, Hillen U, Barkhausen J, Dual AE, Erbel R, Nephrogenic systemic fibrosis. J Am Coll Cardiol 2009;53:1621-8.

Tammaro A, Narcisi A, Tuchinda P, Sina B, Nephrogenic systemic fibrosis following gadolinium administration. Cutis 2015;96:E23-25.

(1) Girardi M, Kay J, Elston D, LeBoit PE, Abdu-Alfa A, Cowper SE, Nephrogenic systemic fibrosis: clinicopathological definition and workup recommendations. J Am Acad Dermatol 2011;65:1095-106.

• Birt-Hogg-Dubé

Aivaz O, Berkman S, Middelton L, Linehan MW, DiGiovanna JJ, Cowen EW, Comedonam and cystic fibrofolliculomas in Birt-Hogg-Dube Syndrome. JAMA dermatol. 2015;151:770-74.

Vernooij M, Claessens T, Luijten M, van Steensel MAM, Coull BJ, Birth-Hogg-Dube syndrome and the skin. Familial cancer 2013;12:381-85.

(1) Vincent A, Farley M, Chan E, James WD, Birt-Hogg-Dube syndrome: a review of the literature and the differential diagnosis for firm facial papules. J Am Acad Dermatol 2003;49:698-705.

(2) Leter EM, Koopmans AK, Gille JJ, van Os TA, Vittoz GG, David EF, et al, Birt-Hogg-Dubé Syndrome: Clinical and Genetic Studies of 20 Families. Journal of investigative Dermatology 2008;128:45-49.

• Porphyria cutanea tardaRobles-Mendez JC, et al. Skin manifestations of chronic kidney disease. Actas Dermosi- filiogr. 2015. http://dx.doi.org/10.1016/j.ad.2015.05.007 - Article in Press.Andersen J, Gjengedal E, Sandberg S, Råheim M. A skin disease, a blood disease or something in between? An exploratory focus group study of patients’ experiences with porphyria cutanea tarda. The

British Journal of Dermatology. 2015;172(1):223-229. (1)Danja Schulenburg-Brand, Ruwani Katugampola, Alexander V. Anstey, Michael N. Badminton, The Cutaneous Porphyrias. Dermatologic Clinics 2014;32(3):369-84.

• Diabetic dermopathy(1) Morgan AJ, Schwartz RA, Diabetic dermopathy: A subtle sign with grave implications. J Am Acad

Dermatol. 2008;58:447-51. (2) McCash S, Emanuel PO, Defining diabetic dermopathy. J. Dermatol 2011;38 (10): 988-92(3) Duff M, Demidova O, Blackburn S, Shubrook J. Cutaneous Manifestations of Diabetes Mellitus. Clinicall Diabetes [serial online]. 2015 Winter 2015;33(1):40-48.

• Calciphylaxis(1) Arseculeratne G, Evans AT, Morley SM. Calciphylaxis--a topical overview. J Eur Acad DermatolVenereol. 2006 May; 20(5):493-502(2) Nigwekar SU, Kroshinsky D, Nazarian RM, Goverman J, Malhotra R, Jackson VA, Calciphylaxis:

Risk factors, diagnosis, and treatment, Am J Kidney Dis 2015;66(1):133-46.(3) Auriemma M, Carbone A, Liberato DL, Cupaiolo A, Caponio C, De Simone C, et al, Treatment of cutaneous calciphylaxis with sodium thiosulfate: two case reports and a review of the literature. Am J Clin Dermatol. 2011;12(5):339-46