Cutaneous Manifestations of Systemic Disease Flashcards

Question

25- A patient is referred for these findings. Which study is the most appropriate in this setting? A. Ceruloplasmin B. Arsenic level C. Iron D. Chest X-ray E. BUN/Cr

Answer 1

Correct choice: A. Ceruloplasmin Explanation: This kodachrome is of blue lunulae, which can occur with zidovudine, silver, or Wilson’s disease. The test for Wilson’s disease would be decreased ceruloplasmin. It is caused by an autosomal recessive ATP7B gene defect (copper-transporting ATPase). It causes an accumulation of copper, resulting in blue lunulae, Kayser-Fleishcher rings, neurologic sequelae, and liver failure. BUN/Cr would evaluate for CKD in half and half nails. Chest X-ray could be used for evaluating pulmonary disease in clubbing. Iron deficiency anemia can cause koilonychia. Arsenic would cause Mee's lines which would present with transverse white lines.

Answer 2

Correct choice: A. Check ASO titer Explanation: This kodachrome and histologic photos show erythema nodosum. Clinically, it presents with erythematous, tender nonulcerating nodules that progress to a violaceous bruise-like color. Histologically it presents with a septal panniculities; one would see septal edema, a mixed inflammatory infiltrate, and widened septa with fibrosis. Streptococcus is the most common infectious cause of erythema nodosum (EN) and therefore ASO titers should be evaluated as a first line diagnostic test for EN. An evaluation of other infectious etiologies, a medication review, and a thorough personal and family history for rheumatologic illnesses should be taken. Excision of erythema nodosum would be an inappropriate first choice, as spontaneous resolution of EN typically occurs within 3-6 weeks. If bruising is suspected, platelet count may be evaluated for thrombocytopenia. However, the pathologic image here indicates a septal panniculitis, which would not occur in thrombocytopenia. HgbA1c could be important if necrobiosis lipoidica diabeticorum is suspected. This would present with well demarcated, firm, waxy, yellowish brown plaques, which is not seen in this photo. TSH would not be the first step in the work-up for erythema nodosum.

Answer 3

Correct choice: A. Hyperthyroidism Explanation:The sign of Hertoghe or Queen Anne's sign is a thinning or loss of the outer third of the eyebrows. It is typically seen in HYPOthyroidism not HYPERthyroidism. Hertoghe's sign can be seen in Ulerythema ophroygenes, hypothyroidism, leprosy, alopecia mucinosa, folliculotrophic MF, ectodermal dysplasia, trichotillomania, and syphilis.

Answer 4

►A Hyperkeratotic follicular nasal papules have been described as a paraneoplastic phenomenon in the setting of multiple myeloma. AML is associated with Sweet's syndrome and Castleman's tumor is associated with paraneoplastic pemphigus.

Answer 5

►A Graves‟ disease is a thyrotoxic condition that results from the production of thyroid-stimulating immunoglobulins (TSI) by stimulated B lymphocytes. The TSI bind to the thyroid-stimulating hormone (TSH) receptor and mimic TSH thereby stimulating thyroid growth and thyroid hormone overproduction. Signs and symptoms of Graves‟ disease include goiter, tachycardia, exophthalmos, tremor, sweating, palpitations, smooth moist skin, diarrhea, sleeplessness, irritability, and weight loss. Autoimmune cutaneous disease may also be associated with Graves disease including vitiligo, dermatitis herpetiformis, herpes gestationis, and pemphigus vulgaris. Cutaneous manifestations of hypothyroidism include xerosis, hyperhidrosis, yellowish hue, myxedema, and purpura. The hair may be dry, brittle and coarse; alopecia may be diffuse and/or involve the lateral eyebrow (madarosis).

Answer 6

►A This patient has dermatitis herpetiformis (DH). DH is characterized by itchy papulovesicles on extensor surfaces of the extremities. Neutrophilic infiltrates at the dermal papillae with vesicle formation are found on histopathologic examination. On immunofluorescence, granular IgA (directed against transglutaminase) deposits are found in perilesional skin. Over 90% of patients have gluten-sensitive enteropathy of varying severity. Dapsone is almost universally therapeutic for the skin disease, but not the enteropathy. A gluten free diet, although difficult to m aintain, treats the enteropathy. The majority of DH patients have the HLA class II DQ2 genotype. On indirect immunofluorescence, one may find antigliadin, antiendomyseal or antireticulin antibodies. Autoimmune thyroid disease (especially Hashimoto”s thyroiditis), enteropathyassociated T-cell non-Hodgkin”s lymphoma and insulin-dependent diabetes are the most common autoimmune associations. Pautrier”s micro-abscesses are found in mycosis fungoides. Leukocytoclastic vasculitis is not a feature of DH.

Answer 7

►D Chronic kidney disease is associated with perforating disorders. These disorder are characterized by pruritus and a biopsy revealing collagen and inflammatory cells broaching the epidermis. The other disorders are not closely associated with perforating diseases.

Answer 8

►E The patient described has IBIDS syndrome (Ichthyosis, Brittle hair, Intellectual impairment, Decreased fertility, and Short stature), or Tay's syndrome. This syndrome is autosomal recessive, caused by mutations in the ERCC2/XPD or ERCC3/XPB genes, resulting in impaired nucleotide excision repair. Cataracts may be a feature. If photosensitivity is a feature (PIBIDS), gonal size is likely normal. Perifoveal glistening white dots are a feature of Sjorgen-Larsson Syndrome, not IBIDS.

Answer 9

►C Congenital hypertrophy of the retinal pigment (CHRPE) is an early feature of Gardner syndrome (GS). It is found in approximately 60% of patients with GS. GS is an autosomal dominant disorder characterized by precancerous intestinal polyposis and subsequent adenocarcinoma of the gastrointestinal tract. Cutaneous manifestations include epidermoid cysts, osteomas, desmoids and fibrous tumors. A mutation in the adenomatous polyposis coli (APC) gene, a tumor suppressor gene, is responsible for the disease. Most patients develop colon carcinoma by the 2nd or 3rd decade. Therefore, prophylactic colectomy is warranted. Mutations in the MSH2 gene are found in Muir-Torre syndrome. Pheochromocytomas are found in multiple endocrine neoplasia (MEN) syndromes IIa and IIb. Tram track calcifications are found in SturgeWeber syndrome. Peg-shaped teeth are found in multiple syndromes including ectodermal dysplasia.

Answer 10

►C Acute intermittent porphyria (AIP) is associated with colicky abdominal pain, neurologic symptoms, and SIADH. This disorder is caused by deficiency of porphobilinogen deaminase. AIP may be exacerbated by drugs including barbiturates, sulfonamides, and griseofulvin, among others.

Answer 11

►C Cronkhite-Canada syndrome is a rare, non-familial disease characterized by patchy alopecia, nail changes or loss, lentigines, inflammatory polyps, abdominal pain, and a protein losing enteropathy.

Answer 12

►A Hypertrichosis lanuginosa acquisita is the abrupt onset of downy, soft, non-pigmented hair of the face, trunk, and extremities. It may have an associated glossitis. It is associated with underlying lung carcinoma and may resolve with treatment of the underlying malignancy.

Answer 13

►E Piebaldism is caused by an autosomal dominant mutation of the proto-oncogene c-KIT which encodes tyrosine a tyrosine kinase receptor on melanocytes, preventing activation by steel factor.

Answer 14

►A Blue rubber bleb nevus syndrome is a rare sporadic or autosomal dominant disorder with soft compressible blue tumors on the trunk and arms. Nocturnal pain is characteristic. Gastrointestinal hemangiomas can cause hemorrhage. Mutations in the VMCM1=TEK=Tie -2 gene are reported. It is also knkow n as VMCM syndrome.

Answer 15

►B Acute intermittent porphyria (AIP) is the second most common porphyria and is caused by a deficiency in porphobilinogen (PBG) deaminase, which is located in the cytosol. Patients suffer from colicky pain, paralysis and psychiatric disorders. There are no specific skin manifestations. PBG and aminolevulenic acid (ALA) are elevated in the urine. Attacks are precipitated by medications such as barbiturates, estrogen, griseofulvin, and sulfonamides as well as starvation, fever and infection. Treatment includes glucose loading and hematin infusion. Congenital erythropoietic porphyria (CEP) or Günter‟s disease is caused by a defect in uroporphyrinogen III synthase, which is found in the cytosol. Patients are extremely photosensitive and erythema, blistering and scarring result. Patients present with red urine early in life along with hypertrichosis and red-stained teeth that fluoresce. Uroporphyrins (URO) are much high than coproporphyrins (COPRO) in the urine. URO is found in the red blood cells (rbcs) and COPRO is found in the stool. The rbcs display stable fluorescence. Porphyria cutanea tarda (PCT) is the most common porphyria and is caused by a deficiency (usually sporadic) in uroporphyrinogen decarboxylase, which is found in the cytosol. Patients present with photosensitivity and blistering of sun-exposed areas, especially the dorsal hands. Hypertrichosis and sclerodermoid changes may occur as well. Liver disease (hepatitis C or alcoholic cirrhosis) is often present and hemochromatosis may be associated. Urine may fluoresce pink or coral-red with Wood‟s lamp. URO>COPRO in the urine and low levels of COPRO are found in the stool. Treatments include phlebotomy, antimalarials, and therapy for liver disease if appropriate. Hereditary coproporphyria (HCP) is caused by a deficiency in coproporphyrinogen oxidase, which is found in the mitochondria. One-third of patients are photosensitive, and patients suffer gastrointestinal and neurological symptoms similar to AIP. Urine COPRO is elevated only with attacks, and COPRO is present in the stool. Variegate porphyria is the result of decreased activity of protoporphyrinogen oxidase, which is present in the mitochondria. It combines the skin lesions of PCT with the systemic manifestations of AIP. Urine COPRO:URO is 1:1 or COPRO> URO to distinguish it from PCT, and PROTO is found in the stool. The plasma fluoresces at 626nm. Precipitators and treatments are similar to AIP. Erythropoietic protoporphyria (EPP) is caused by ferrochetalase deficiency, which is present in the mitochondria. Patients experience immediate burning of the skin with sun exposure. Protoporphyrin IX, the only oxidized porphyrin in the heme pathway and absorbs in the Soret band (400-410nm). Patients have erythematous plaques in a photo-distribution. Urine porphyrins are normal. PROTO is found in the rbcs and the stool. Excessive porphyrins deposited in the liver lead to gallstones and cirrhosis. Beta carotene may helpful. Hepatoerythropoietic porphyria (HEP) is essentially a homozygous form of PCT, with deficiency in uroporphyrinogen decarboxylase. It is clinically similar to CEP with red urine and hypertrichosis, vesicles and scarring of sun-exposed skin. URO is present in the urine and COPRO in the stool. PROTO is present in rbcs which distinguishes it from CEP, which was URO in rbcs.

Answer 16

►E The histologic findings of necrobiosis lipodica diabeticorum are: dermal granulomatous inflammation in a horizontal pattern, collagen degeneration, and normal or atrophic epidermis.

Answer 17

►E Basex syndrome, also Acrokeratosis paraneoplastica, presents with symmetric erythematous, nearly violaceous, psoriasiform dermatoses of the hands, feet, ears and nose. The syndrome is nearly associated with an underlying malignancy, usually squamous cell carcinoma of the upper aerodigestive tract.

Answer 18

►E Necrobiosis Lipoidica Diabeticorum (NLD) is found in 0.3-3% of diabetics. Approximately 20% of NLD patients have diabetes or glucose intolerance. It presents with single or mul tiple redbrown papules which progress to sharply demarcated yellow-brown atrophic, telangiectatic plaques with violaceous, irregular borders; common sites include the shins. Cutaneous anesthesia, hypohidrosis, and partial alopecia can be found. Pathology shows palisading granulomas containing degenerating collagen (necrobiosis); with NO increase in dermal mucin. There is no impact of tight glucose control on the likelihood of developing NLD.

Answer 19

►E Hepatitis C virus (HCV) is a single-stranded RNA virus that is a member of the flaviviridae family. Approximately 20-30% of patients develop symptoms with acute infection and 70% will progress to chronic disease. Porphyria cutanea tarda or PCT is associated with HCV in a substantial percentage of patients; in one study, antibodies to HCV were found in 82% of PCT patients. Up to 80% of mixed cryoglobulinemia (MC) cases are associated with HCV. The incidence of lichen planus in HCV patients varies from region to region (0.1-35%). The histopathology of MC lesions is leukocytoclastic vasculitis. Another relatively common association is polyarteritis nodosa (PAN) which is also related to hepatitis B infection. Finally, generalized pruritis is a common complaint of HCV patients.

Answer 20

►C Pyoderma vegetans consists of vegetating plaques and vesicopustules of intertriginous areas than heal with hyperpigmentation. When the process involves mucosal surfaces it is called pyostomatitis vegetans. These processes are both associated with ulcerative colitis, not Crohn's disease.

Answer 21

►A Patient with NF 1 who have multiple juvenile xanthogranulomas are at 20 times greater risk for developing juvenile chronic myelogenous leukemia.

Answer 22

►D The Soret band (400-410 nm) is the portion of ultraviolet wavelengths at which most porphyrins are most sensitive.

Answer 23

►D Patients with Type III hyperlipidemia have both elevated triglyceride levels and cholesterol levels in the plasma. A genetic basis for the primary disorder, familial dysbetalipoproteinemia, has been well established. These patients present as adults with premature atherosclerosis and xanthomas, particularly plane (palmar) xanthomas.

Answer 24

►A Acrokeratosis Paraneoplastica (aka Bazex) is always associated with malignancy. Most commonly, the associated malignancy is a squamous cell carcinoma of the upper aerodigestive tract. The skin disease usually follows the course of the malignancy.

Answer 25

►C Werner‟s syndrome or Adult Progeria is caused by autosomal recessive mutations in WRN (Recql2) gene, which encodes DNA helicase. This defect leads to defects in DNA repair and replication. Patients prematurely age and essentially experience many diseases of aging early in childhood and teen years. They exhibit tight atrophic skin, relatively large heads for body size, leg ulcers and cannities. Patients experience early, accelerated atherosclerosis leading to death by myocardial infarction. In addition, type II diabetes, cataracts, osteoarthritis, osteoporosis and hypogonadism are features.

Answer 26

►A Nephrogenic systemic fibrosis is a chronic fibrosing disorder seen most commonly in the setting of renal failure. There is a reported association also with gadolinium as contrast in an MRI. Patients present with woody indurated plaques or nodules primarily of the extremities, with occasional involvement of the trunk. Fulminant and fatal disease is rare, occurring in about 5% of cases. Death is due to impaired ventilation secondary to fibrosis of respiratory muscles.

Answer 27

►D Pityriasis rotunda is an dermatosis that features characteristic discrete, circular, scaly, brown patches on the trunk and extremities. Pityriasis rotunda may be associated with systemic diseases in certain racially predisposed groups (blacks), and has been linked to hepatocellular carcinoma.

Answer 28

►A This patient has Montgomery's syndrome, or xanthoma disseminatum, which is characterized as a benign normolipidemic but disfiguring condition that demonstrates an eruption of 100's of redbrown yellowish papules and plaques that may involve the mucous membranes. These patients should be evaluated for diabetes insipidus. Benign cephalic histiocytosis shows brownish-yellow papules on the upper face. Rosai-Dorfman, or sinus histiocytosis with massive lymphadenopathy, features polymorphic papules and plaques in the first two decades with fever, increased ESR, and cervical lymphadenopathy. Necrobiotic xanthogranuloma is characterized by red-orange plaques that may ulcerate. Finally, multicentric reticulohistiocytosis features coral beading around the fingers and is associated with arthritis mutilans and malignancy.

Answer 29

►C Connective tissue dystrophic calcifications, increased estrogen levels, hypertrichosis and sclerodermoid changes are all associated with porphyria cutanea tarda, but sclerodermoid changes are the only finding with a direct relationship to urine uroporphyrin levels. Urine fluorescence occurs in PCT, not RBC fluorescence.

Answer 30

►D Cronkhite-Canada is an aquired disease characterized by the development of polyps throughout the GI tract. Patients can present with hyperpigmented macules as well as the sequella of GI malabsorption. The malignant transformation of polyps can occur.

Answer 31

►D Defects in many of the enzymes involved in heme synthesis are responsible for porphyrias. The first and last three steps of the heme synthesis pathway occur in the mitochondria.

Answer 32

►B Hyperkeratotic follicular nasal papules are associated with multiple myeloma. A sudden increase in number and size of seborrheic keratoses is called the sign of Lesser-Trelat and can be seen in gastric or colon carcinoma. Erythema and vesiculation in periorificial and acral areas is characteristic of necrolytic migratory erythema most often associated with pancreatic cancer. Concentric erythematous rings with trailing scale is a feature of erythema gyratum repens most commonly seen in lung cancer. Tripe palms with AN more likely gastric whereas without AN more likely lung.

Answer 33

►B Patients with Rothmund thompson have early photosensitivity and poikilodermatous skin changes, juvenile cataracts, skeletal dysplasias, and a predisposition to osteosarcoma and skin cancer. Patients with Bloom syndrome have an increased risk for G I malignancies and lymphoma. Patients with xeroderma pigmentosum can develop ocular melanoma. Patients with Werner syndrome can develop thyroid and hematologic malignancies, sarcomas,and meningiomas. Cockayne syndrome patients have photosensitivity, short stature, premature aging, visual problems, neurologic deficits, but no internal malignancies.

Answer 34

►C Riga-Fede disease is a benign ulcerative granulomatous process that occurs in reaction to chronic, repetitive trauma of the oral mucosa by the teeth. Clinically, it appears as firm, verrucous plaques. It may be associated with an underlying developmental anomaly or underlying neurologic disorder.

Answer 35

►C Varicella zoster virus is the causative agent in chicken pox and shingles, where recrudescence from latency in the dorsal root ganglion causes a dermatomal distribution of painful vesicles and erosions. Biopsy of herpes viruses reveals cells with multinucleation, margination of the chromatin, and Cowdry Type A bodies, which are intranuclear eosinophilic amorphous bodies surrounded by a clear halo.

Answer 36

►A The most common autoimmune disease seen in association with Hepatitis C is autoimmune thyroiditis.

Answer 37

►E Cockayne Syndrome is an autosomal recessive disorder caused by a mutation of an unknown gene that results in the inability to repair cyclobutane dimers induced by UV exposure. Cutaneous findings include photosensitivity, "bird-headed" facies, and "Mickey Mouse" ears. Statements A-D are true regarding the syndrome.

Answer 38

►D Patients with diabetes mellitus (DM) may develop thickened skin and tightened joints. Scleredema is occasionally seen in type II diabetics and presents with a peau d‟orange texture and appearance on the upper back. Perhaps as many as 20% of those with necrobiosis lipoidica diabeticorum(NLD) have diabetes, but only 0.3% to 3% of diabetics have NLD. The most common skin manifestation of DM is diabetic dermopathy, or skin hyperpigmentation, normally on tibial surfaces. Eruptive xanthomas, which are associated with high triglycerides are occasionally seen as are generalized or perforating granuloma annulare.

Answer 39

►C Erythropoietic Protoporphyria (EPP) is characterized by a burning sensation experienced immediately upon photoexposure. Biopsy reveals PAS-positive hyalinization of the superficial dermal vessel walls. Atrophe blance appears similar histologically but is not characterized by photosensitivity. The other disorders exhibit different histopathologic findings than described.

Answer 40

►E Erythema gyratum repens presents more commonly in men than in women, and appears clinically as concentric erythematous rings with trailing scale on the trunk and proximal extremities. The skin is described as having a "wood grain" appearance. Skin findings often precede the diagnosis of an associated malignancy. Lung carcinoma is the most commonly associated malignancy, but it has also been reported in association with breast, cervical, bowel, prostate, gastric/bowel and bladder cancer.

Answer 41

►D This patient has carcinoid sydrome, which presents with facial flushing, diarrhea, and intermittent bronchospasm. Patients can also develop telangiectasia, pellagra-like, or sclerodermoid-like cutaneous findings. This syndrome is caused by a neoplasm originating in the endocrine argentaffin cells. 80-85% are found in the GI tract. Treatment is surgical removal of the tumor, or medical treatment with medications including somatostatin, methylsergide, cyproheptadine, beta-blockers, and phenothiazine derivatives.

Answer 42

►D Patient has Cronkhite-Canada syndrome. This is a syndrome with a sporadic mutation. Patients develop GI symptoms(diarrhea, malabsorption, polyposis), weight loss and weakness. Later on they develop cutaneous changes such as melanocytic macules on the fingers, generalized hyperpigmentation and alopecia

Answer 43

►E Approximately 30% of diabetic patients have cutaneous manifestations of their disease. Diabetic dermopathy, or “shin spots” is the most common cutaneous association with diabetes. Patients are generally long-standing diabetics, and are associated with symmetrical brownish, atrophic plaques on the shins. Acanthosis nigricans is more common in black and Hispanic diabetics, and may be a component of the HAIRAN (hyperandrogen, insulin resistance, acanthosis nigricans) syndrome. Hyperpigmented velvety plaques are most often found in the flexures. Waxy, thick skin and limited joint mobility are both related to poor glucose control. Scleredema diabeticorum, which most often causes thickened plaques of the upper back and neck most often affects type II diabetics. Necrobiosis lipoidica diabeticorum (NLD) is present in only 0.3 to 3% of diabetics, but perhaps 20% of patients with NLD have diabetes or glucose intolerance. Sharply-demarcated yellow-brown, telangiectatic plaques are found on the tibial surfaces. Ulceration may occur. Yellow skin may affect approximately 10% of diabetics and presents diffusely. Serum carotene levels may be elevated. Perforating disorders may be related, especially in the setting of renal disease. In the setting of hypertriglyceridemia, eruptive xanthomata may be present. The association between diabetes and granuloma annulare (GA) is controversial. If truly an association, the generalized and perforating forms of GA are most commonly associated. Infectious associations include candidiasis, which may present an angular cheilitis, chronic paronychia, interdigital or intertriginous disease. Cutaneous bacterial infections, including group A and B streptococci, pseudomonas aerugenosa and corynebacterium are more common. Dermatophyte infections are not more common, although tinea pedis may increase the risk for cellulitis in diabetic patients. Finally, rhinocerebral mucormycosis is a potential disasterous complication of uncontrolled hyperglycemia with ketoacidosis. Mortality rates can approach 35%.

Answer 44

►E All of the above are non-specific cutaneous manifestations of hypothyroidism: an increase in percentage of telogen hairs, yellowish hue caused by carotenemia, purpura secondary to impaired wound healing, and loss of the lateral third of the eyeborw (madarosis).

Answer 45

►C Carcinoid syndrome is caused by a tumor originating in the endocrine argentaffin cells. In order of descending frequency, the most common locations are appendix > small bowel > rectum. Patients experience facial flushing that descends anatomically, diarrhea, hyperhidrosis and bronchial reactivity. A pellagra-like eruption may occur as well as telangiectasia and sclerodermoid changes. Patients experience symptoms once the disease metastasizes to the liver or if it did not involve the GI tract initially. Diagnosis can be made finding elevated 5hydroxyindolacetic acid (5-HIAA) in the urine. Nitrosonaphthol turns urine purple if 5-HIAA levels are significantly elevated, and can be used as a screening test. Bananas, tomatoes, plums, avocadoes and eggplant can increase levels of 5-HIAA. Treatment involves removal of the tumor along with medical therapy if appropriate. Agents used include somatostatin, methylsergide, cyproheptadine, and beta blockers. Vanillylmandelic acid (VMA) is an important urinary metabolic product of epinephrine and norepinephrine and is detected in the diagnosis of pheochromocytoma.

Answer 46

►A Henoch-Schonlein Purpura (HSP) is an IgA mediated small vessel vasculitis. Clinically, patients present with palpable purpura of the lower extremities and buttocks, GI vasculitis, and glomerulonephritis.

Answer 47

►D Acute intermittent porphyria (AIP) is the second most common porphyria and is caused by a deficiency in porphobilinogen (PBG) deaminase, which is located in the cytosol. Patients suffer from colicky pain, paralysis and psychiatric disorders. There are no specific skin manifestations. PBG and aminolevulenic acid (ALA) are elevated in the urine. Attacks are precipitated by medications such as barbiturates, estrogen, griseofulvin, and sulfonamides as well as starvation, fever and infection. Treatment includes glucose loading and hematin infusion. Congenital erythropoietic porphyria (CEP) or Günter‟s disease is caused by a defect in uroporphyrinogen III synthase, which is found in the cytosol. Patients are extremely photosensitive and erythema, blistering and scarring result. Patients present with red urine early in life along with hypertrichosis and red-stained teeth that fluoresce. Uroporphyrins (URO) are much high than coproporphyrins (COPRO) in the urine. URO is found in the red blood cells (rbcs) and COPRO is found in the stool. The rbcs display stable fluorescence. Porphyria cutanea tarda (PCT) is the most common porphyria and is caused by a deficiency (usually sporadic) in uroporphyrinogen decarboxylase, which is found in the cytosol. Patients present with photosensitivity and blistering of sun-exposed areas, especially the dorsal hands. Hypertrichosis and sclerodermoid changes may occur as well. Liver disease (hepatitis C or alcoholic cirrhosis) is often present and hemochromatosis may be associated. Urine may fluoresce pink or coral-red with Wood‟s lamp. URO>COPRO in the urine and low levels of COPRO are found in the stool. Treatments include phlebotomy, antimalarials, and therapy for liver disease if appropriate. Hereditary coproporphyria (HCP) is caused by a deficiency in coproporphyrinogen oxidase, which is found in the mitochondria. One-third of patients are photosensitive, and patients suffer gastrointestinal and neurological symptoms similar to AIP. Urine COPRO is elevated only with attacks, and COPRO is present in the stool. Variegate porphyria is the result of decreased activity of protoporphyrinogen oxidase, which is present in the mitochondria. It combines the skin lesions of PCT with the systemic manifestations of AIP. Urine COPRO:URO is 1:1 or COPRO> URO to distinguish it from PCT, and PROTO is found in the stool. The plasma fluoresces at 626nm. Precipitators and treatments are similar to AIP. Erythropoietic protoporphyria (EPP) is caused by ferrochetalase deficiency, which is present in the mitochondria. Patients experience immediate burning of the skin with sun exposure. Protoporphyrin IX, the only oxidized porphyrin in the heme pathway and absorbs in the Soret band (400-410nm). Patients have erythematous plaques in a photo-distribution. Urine porphyrins are normal. PROTO is found in the rbcs and the stool. Excessive porphyrins deposited in the liver lead to gallstones and cirrhosis. Beta carotene may helpful. Hepatoerythropoietic porphyria (HEP) is essentially a homozygous form of PCT, with deficiency in uroporphyrinogen decarboxylase. It is clinically similar to CEP with red urine and hypertrichosis, vesicles and scarring of sun-exposed skin. URO is present in the urine and COPRO in the stool. PROTO is present in rbcs which distinguishes it from CEP, which was URO in rbcs.

Answer 48

►C Fabry‟s disease is an X-linked lysosomal disorder that leads to excessive deposition of neutral glycosphingolipids in the vascular endothelium. The disorder is caused by a deficiency of alphagalactosidase-A leading to progressive endothelial accumulation of glycosphingolipids. This accumulation accounts for the associated clinical abnormalities of skin, eye, kidney, heart, brain, and peripheral nervous system. Acroparesthesias are a frequent presenting symptom of Fabry‟s disease. The primary cutaneous manifestation are angiokeratomata (angiokeratoma corporis diffusum), which are most common in a “bathing-trunk” distribution. Lens opacities and retinal and conjunctival vascular malformations may be found in the eyes. Patients may experience cardiac disease, stroke or renal failure.

Answer 49

►E Addison disease is caused by destruction of the adrenal glands by any cause. Tuberculosis used to be the primary cause, now the most common cause is auto-immune destruction. Other causes of adrenal gland destruction include; coccidiomycosis, cryptococcosis, histoplasmosis, sarcoidosis, metastatic tumor and amyloidosis.

Answer 50

►D Trichorhinopharyngeal syndrome is the only condition from the mentioned conditions that is not associated with saddle nose deformity.It is associated with sparse hair, a bulbous (pearshaped) nose and cone-shaped epiphyses.

Answer 51

►E Patients with hepatitis C virus (HCV) may experience numerous cutaneous manifestations of their internal disease. Cryoglobulinemia (CG) may result in small vessel leukocytoclastic vasculitis. Types of CG include: type I, which is monoclonal IgM; type II, which is polyclonal IgG and monoclonal IgM; type III, which is polyclonal IgG and polyclonal IgM. Mixed CG is the most commonly associated type of CG with HCV. Patients often have a positive rhematoid factor and have C3 complement decreased. Other diseases associated with HCV include porphyria cutanea tarda, lichen planus and polyarteritis nodosa. Thyroid-related dermopathy results in increased hyaluronic acid in the dermis. Lindsay's nails, or half and half nails, are associated with renal disease. Congenital hyperpigmentation of the retinal pigment (CHRPE) is seen in Gardner's syndrome. Peutz-Jeghers, among other conditions presents with periorificial lentigines.

Answer 52

►B Lichen planus of the oral mucosa is most highly associated with Hepatitis C Infection. Biopsies of lichen planus on the oral mucosa may exhibit plasma cells and parakeratosis, unlike cutaneous lichen planus. The other disorders are not as closely related to oral lichen planus.

Answer 53

►A Eruptive xanthomas generally occur in patients with triglyceride levels of 2000mg/dl or greater. Associations include poorly-controlled diabetes mellitus, retinoids, estrogens, excessive alcohol consumption (leading to pancreatitis) and familial hyperlipidemias types I, IV and V. Clinically, they appear as crops of firm, non-tender yellowish papules with an erythematous border. Most commonly, they occur on the extensor surfaces, but they can be diffuse. A reduction in triglycerides and/or tight glucose control usually results in a reduction in the number of lesions.

Answer 54

►E Patients with Cowden's Syndrome (multiple hamartoma syndrome) are at increased risk for Lhermite Duclos disease (dysplastic gangliocytoma of the cerebellum). c

Answer 55

►C This patient has eruptive xanthomas, a condition which is classically associated with elevated serum triglycerides.

Answer 56

►B Necrolytic migratory erythema or glucagonoma syndrome is clinically characterized by periorificial and acral erythema, vesicles, pustules and erosions. A circinate pattern is often seen. Glossitis and cheilitis are features as well. The underlying tumor is an alpha-2 glucagon producing islet cell pancreatic carcinoma, which is metastatic at the time of diagnosis in the majority of cases. Histopathological findings include dyskeratotic keratinocytes in the stratum granulosum, acanthosis and parakeratosis. Serum glucagon levels are elevated. The tumors must be resected if feasible, and intravenous somatostatin and amino acids have been used for treatment.

Answer 57

►C Cronkhite-Canada syndrome (CCS) is a rare, sporadically occurring, non-inherited disorder characterized by generalized gastrointestinal polyps, cutaneous pigmentation, alopecia, and onychodystrophy. The pathogenesis is unknown. The GI polyps are hamartomatous and malignant degeneration is unusual. Cutaneous signs include circumscribed lentiginous hyperpigmentation, alopecia and nail dystrophy. Often, symptoms appear in the sequence of gastrointestinal symptoms, weight loss, weakness, edema, and then cutaneous changes after weeks or months. CCS is a progressive disease, and often carriers a poor prognosis primarily because of difficulties with fluid and electrolyte management. Fibrocystic breast disease is associated with Cowden”s disease (multiple hamartoma syndrome).

Answer 58

►A Clear cell syringomas are associated with diabetes mellitus. Eruptive syringomas may arise in patients with skin type V and VI and in patients with Down‟s syndrome. The other disorders are not associated with syringomas.

Answer 59

►A Acquired perforating dermatosis is the transepidermal elimination of altered dermal substances. The etiology is unknown, but may be related to micro-deposits of calcium with subsequent evacuation through the epidermis. It is more commonly seen in darker skin types and in patients with ESRD secondary to diabetic nephropathy.

Answer 60

►E Dermatomyositis is characterized by proximal muscle weakness and a constellation of cutaneous findings. Skin findings include periorbital edema and poikiloderma (heliotrope), Gottron‟s sign and papules, nail fold telangiectasia, cuticular dystrophy, poikiloderma in a shawl distribution and photosensitivity. Psoriasiform dermatitis and scaling of the palms and soles may occur-NOT on the scalp! Children more often display calcinosis cutis and vasculitis. Within the first 3 years of diagnosis there is a higher likelihood of malignancy. Women are at risk for ovarian and breast carcinoma, and men are at risk for gastric carcinoma and lymphoma. Diagnostic findings include elevated creatine kinase (CK) and aldolase, inflammatory muscle biopsy changes or abnormal muscle MRI, and abnormal EMG. Treatment includes corticosteroids, methotrexate and other immunosuppressive medications.

Answer 61

►B In Cushing's Syndrome, corticotropin is NOT suppressed with the administration of dexamethasone. The other statements are true.

Answer 62

►C The shoulder pad sign has been described in the setting of late systemic amyloidosis and is due to the direct deposition of amyloid in the deltoid muscles.

Answer 63

►B Paraneoplastic pemphigus has been associated with Non-Hodgkins lymphoma, chronic lymphocytic leukemia, thymoma, Castleman's tumor, and sarcoma. It has not been associated with lung carcinoma. Treatment includes management of the underlying malignancy, as well as prednisone or other immunosuppressive agents.

Answer 64

►D Erosive mucosal variant of lichen planus has the strongest association with HCV. The pathogenesis of pruritus in the setting of chronic HCV infection may be related to elevated bile salt levels in the setting of liver failure, but there is not always a direct correlation between serum bile salt level and degree of pruritus. Polyarteritis nodosa is associated with both HCV infection and hepatitis B virus infection. Statement D is correct. Cutaneous reactions to HCV treatment are more common with interferon/ribavirin combination treatment than with treatment with interferon alone.

Answer 65

►B Howel-Evans syndrome is an autosomal dominant disorder that presents with diffuse waxy keratoderma of the palms and soles, as well as oral leukoplakia and squamous cell carcinoma arising from keratodermic skin. It is associated with esophageal carcinoma; cancer screening in family members is advised.

Answer 66

►D Eosinophilia develops within 3 days of embolization in 70-80% of patients and may remain elevated for up to 1 month. Patients with cholesterol emboli typically have an elevated ESR and C- reactive protein as well. Leukocytosis can also be seen in up to half of patients.

Answer 67

►C Paraneoplastic pemphigus (PNP) is characterized by painful stomatitis, which is extremely resistant to therapy. Cutaneous lesions are variable and can include flaccid or tense bullae, targetoid lesions or lichenoid eruptions. PNP is associated with the following neoplasms (in descending order of frequency): non-Hodgkins lymphoma, chronic lymphocytic leukemia, Castleman‟s disease and malignant and benign thymus tumors. Histopathologic findings include suprabasal acantholysis, dyskeratosis and vacuolar interface with a lichenoid infiltrate. Direct immunofluorescence of perilesional skin demonstrates intercellular and granular IgG and granular C3 at the dermoepidermal junction. The preferred substrate for indirect immunofluorescence is rat bladder and intercellular IgG is found. Target antigens include desmoplakin (250kD), envoplakin (210kD), bullous pemphigoid antigen-1 (230kD), periplakin (190kD), and desmogleins 1 and 3. Many patients succumb to the underlying cancer. Treatment requires management of the malignancy and immunosuppressive agents.

Answer 68

►D Waardenburg Syndrome is an autosomal dominant disorder. Sjorgen-Larsson Syndrome is an autosomal recessive disorder characterized by a triad of ichthyosis, di- or tetraplegia, mental retardation. Refsum Disease is an autosomal recessive disorder whose features include deafness, mild ichthyosis in adulthood, and accentuated palmar creases. Bjornstad's Syndrome is an autosomal recessive disorder characterized by pili torti and deafness. Cockayne Syndrome is an autosomal recessive disorder whose features include photosensitivity, bird-headed facies, and "Mickey-Mouse" ears, as well as deafness.

Answer 69

►E Perhaps 0.3 to 3% of diabetics have NLD, whereas approximately 20% of NLD patients have diabetes or glucose intolerance. The split in bullous diabeticorum is normally either intraepidermal or subepidermal. C. albicans is the most common cause of diabetes-related yeast infections. The association between GA and diabetes is controversial, but if the two are related, generalized and perforating GA have been implicated. Yellow skin may occur in up to 10% of diabetic patients and is characterized by diffuse yellow-orange skin. Half of these patients have elevated serum carotene levels. The suggested is cause is elevated consumption of yellow fruits and vegetables in the setting of impaired hepatic metabolism of carotene and subsequent non- enzymatic glycosylation of dermal collagen.

Answer 70

►A Chilblain lupus is a rare manifestation of lupus erythematosus. Lesions resemble common pernio clinically, but should have histological findings consistent with lupus, such as interface changes. These lesions may not resolve upon warming and often respond poorly to other lupus treatments such as antimalarials. c

Answer 71

►C The most common location for lesions of nephrogenic fibrosis dermopathy is the lower extremities.

Answer 72

►A Turcot syndrome is a variant of HNPCC-hereditary nonpolyposis colorectal cancer, Lynch syndrome with the homozygous mutations in MSH2, MSH6, MLH1, PMS2 as opposed to heterozygous mutaitons in HNPCC. It is characterized by polyposis and brain cancer. Patients may also exhibit other clinical features of HNPCC syndrome. Both patients with Lynch Syndrome and Turcot Syndrome necessitate a colon cancer work-up. c

Answer 73

►A The rate-limiting step in the heme synthesis pathway is the synthesis of delta aminolevulanic acid from glycine and succinyl CoA via aminolevulinic acid synthase. This step takes place in the mitochondria. Porphobillinogen deaminase is defective in acute intermittent porphyria, coproporphyrinogen oxidase in hereditary coproporphyria and protoporphyrinogen oxidase in variegate porphyria.

Answer 74

►B Reduced matabolism of beta-carotene in the diet, can result in yellowing of the skin in hypothyroidism. Treatment of porphyria with beta-carotene can result in carotenemia. Pretibial myxedema, Grave”s disease and amyloidosis do not result in carotenemia. c

Answer 75

►D Basal cell nevus syndrome (Gorlin syndrome) is caused by an autosomal dominant mutation in PTCH gene that encodes PTC protein involved in sonic hedge hog pathway. This mutation leads to loss of inhibition of smoothened (SMO) leading to an increased expression of other genes. Cutaneous findings include nevoid basal cell carcinomas, milial cysts, epidermoid cysts and palmar- plantar pits. Neurological findings include calcifications of the falx cerebri, agenesis of the corpus callosum, mental retardation, medulloblastoma and spina bifida. Ocular findings include blindness, cataracts, colobomas and strabismus. Other findings include odontogenic cysts of the jaw, frontal bossing, bifid ribs, and pectus deformity. NEMO gene mutations are found in incontinentia pigmenti. Tram-track calfications are seen Sturge-Weber syndrome. Telangiectasias are seen in ataxia-telangiectasia among others.

Answer 76

►A Florid cutaneous papillomatosis is the rapid onset of numerous wart-like lesions on the backs of the hands and wrists that is associated with pruritus, acanthosis nigricans, and the sign of LeserTrelat. All reported cases are associated with internal malignancy, most commonly gastric carcinoma. Follicular papules on the nose are seen in multiple myeloma. Carpal tunnel syndrome and periorbital purpura can be seen in primary systemic amyloidosis with multiple myeloma. migratory thrombophlebitis is associated with pancreatic cancer. c

Answer 77

►C An uncommon complication of treatment with potassium iodide is the Wolff-Chiakoff effect.

Answer 78

►C Blue rubber bleb nevus is associated with soft and compressible blue nodules 0.1 to 5 cm in size. The cutaneous lesions typically appear in childhood, and they do not regress with time. The venous malformations are mainly asymptomatic but can be painful when thrombosis occurs. The venous malformations also involve the gastrointestinal tract, most commonly the small bowel, where they are friable and can bleed.

Answer 79

►E Castleman‟s tumor is the most common cause of paraneoplastic pemphigus in children. Paraneoplastic pemphigus presents with painful stomatitis and varied skin lesions. Indirect immunofluorescence with rat bladder substrate shows intercellular IgG.

Answer 80

►B All of the statements regarding dermatitis herpetiforms, or "Duhring's Disease," are true except for statement B. Virtually all DH patients have gluten-sensitive enteropathy, although only 20% of them have symptoms (such as diarrhea, steatorrhea, weight loss, bloating, and malabsorption).

Answer 81

►A The patient has necrobiotic xanthogranuloma. Lesions develop periorbitally and in flexural areas, often extend deeply into the dermis or subcutis, and heal with scarring. These lesions are typically associated with a monoclonal gammopathy, usually IgG. Patients with necrobiotic xanthogranuloma rarely develop myeloma. Leukopenia and hepatosplenomegaly are also often seen.

Answer 82

►A Vohwinkles Syndrome is an autosomal dominant disorder caused by a mutation of the GJB2 gene which encodes Connexin 26. Clinical features include deafness, as well as the cutaneous findings described in choice A.

Answer 83

►A Distribution of lesions in calciphylaxis may predict prognosis; those with acral lesions have a better outcome than those with proximally located lesions.

Answer 84

►D Cushing syndrome is caused by excess levels of either exogenously administrated glucocorticoids or endogenous overproduction of cortisol. The syndrome is most commonly caused by the therapeutic administration of exogenous glucocorticoids. The term "Cushing's disease" is reserved for Cushing's syndrome that is caused by excessive secretion of adrenocorticotropin hormone (ACTH) by a pituitary tumor, usually an ad enoma. Other endogenous sources include an adrenal tumor and other malignancies (i.e. oat cell carcinoma of the lung). Patients develop moon facies, facial plethora, supraclavicular fat pads, buffalo hump, truncal obesity, and striae. In addition, proximal muscle weakness, easy bruising, weight gain, hirsutism, and, in children, growth retardation may occur. Systemic sequelae include hypertension, osteopenia, diabetes mellitus, and impaired immune function. Excess endogenous or exogenous glucocorticoids can result in a leukocytosis and hypokalemic metabolic acidosis. Urine cortisol levels 3 to 4 times normal are diagnostic. The dexamethasone suppression test is a valuable diagnostic tool. For this study, 1mg is given at 11pm and the 8am cortisol level is tested. A level of >10 ìg/dL is diagnostic. In patients with Cushing‟s disease, the dexamethasone does not suppress corticotropin. Corticotropin-releasing hormone (CRH) stimulation test is also used to distinguish patients with pituitary adenomas and those with ectopic ACTH syndrome or cortisol-secreting adrenal tumors.

Answer 85

►A Porphyria cutanea tarda (PCT) is caused by a deficiency in the enzyme uroporphyrinogen decarboxylase. Phlebotomy is the treatment of choice and may improve enzymatic activity by removing iron, an inhibitor of the enzyme. Antimalarials and erythropoietin are alternative therapies. Oral iron supplementation may worsen PCT. Naproxen is a common cause of pseudoporphyria.

Answer 86

►E Multiple endocrine neoplasia (MEN) syndromes are divided into types I, IIa and IIb. All are autosomal dominantly inherited. Type I is associated with mutations in MENI; type IIa and IIb involve mutations of RET, which encodes a tyrosine kinase receptor. Type I has the following cutaneous features: facial angiofibromas, collagenomas, lipomas, hypopigmented macules and café- au-lait macules. Type IIa displays macular amyloidosis, while IIb features multiple mucosal neuromas. Systemic features of t ype I include peptic ulcer disease (as part of Zollinger-Ellison syndrome), parathyroid hyperplasia or adenoma, pancreatic tumors and pituitary neoplasia. Type IIa is characterized by Zollinger-Ellison syndrome, medullary thyroid carcinoma, pheochromocytoma, and parathyroid neoplasia. Type IIb displays marfanoid habitus, Hirschsprung disease, medulloblastoma, medullary thyroid carcinoma, pheochromocytoma and ocular neuromas.

Answer 87

►B Tripe palms are rugose thickening of the palms which are nearly always associated with internal malignancy. When tripe palms are present without other cutaneous findings, the most likely internal malignancy is lung cancer. Tripe palms in association with acanthosis nigricans is most likely to be associated with gastric cancer.

Answer 88

►A This slide shows pretibial myxedema in a patient with Grave’s disease. Pretibial myxedema is a form of diffuse mucinosis in which there is an accumulation of excess glycosaminoglycans in the dermis and subcutis of the skin. Glycosaminoglycans, also called mucopolysaccharides, are complex carbohydrates that are important for tissue hydration and lubrication. The main glycosaminoglycan in pretibial myxedema is hyaluronic acid, which is made by cells called the fibroblasts. Pretibial myxedema is also known as localized myxedema, thyroid dermopathy, and infiltrative dermopathy. It is most commonly seen on the shins (pretibial areas) and is characterized by swelling and lumpiness of the lower legs.

Answer 89

►A Tuberous sclerosis is an autosomal dominant disorder with seizures, mental retardation, and characteristic skin findings, including hypopigmented macules, facial angiofibromas, periungual fibromas, and collagenomas. The most common associated tumor is renal angiomyolipoma. Rarely, renal cell carcinoma can develop.

Answer 90

►D Chronic renal failure is the most common internal systemic cause of pruritus. Up to 49% of patients with chronic renal failure have pruritus. Other systemic causes of pruritus include liver disease, hepatitis C, hypo and hyperthryoidism, iron deficiency anemia, polycyhtemia vera, Hodkin's lymphoma, leukemia, carcinoid, internal malignancy, AIDS, and internal parasites.

Answer 91

►E Sipple syndrome (multiple endocrine neoplasia type 2A) is an autosomal dominant disorder characterized by the development of pheochromocytomas, medullary thyroid carcinomas, and hyperparathyroidism. The associated mutation is found in the RET proto-oncogene. An early cutaneous manifestation includes the development of lichen or macular amyloidosis (both keratin- derived cutaneous amyloidoses) often localized to interscapular patches, which may be pruritic (similar to notalgia paresthetica). The latter arises during teenage years and may be the earliest presenting sign of this disease.

Answer 92

►E Peutz-Jeghers Syndrome is an autosomal dominant syndrome. 50% of patients have mutations in the STK11 gene which encodes a serine threonine kinase. It presents with periorificial and mucosal lentigines beginning in infancy, as well as hamartomatous intestinal polyps with intussusception and bleeding; gallbladder, pancreatic, breast, ovarian, and testicular cancer.

Answer 93

►E The Wolff-Chaikoff effect is described as the binding of excess organic iodide in the thyroid gland with resultant inhibition of thyroid hormone synthesis. This can occur in the setting of patients with erythema nodosum (or other inflammatory dermatoses) being treated with potassium iodide.

Answer 94

►C Grave‟s disease is associated with pretibial myxedema. Pathology reveals diffuse increased mucin in the dermis, without increased fibroblasts as seen in scleromyxedema and nephrogenic systemic fibrosis. The other disorder are not associated with pretibial myxedema.

Answer 95

►A Cutaneous neurofibromas typically appear after puberty. The absence of neurofibromas in young children does not rule out this diagnosis. Pigmented iris hamartomas are more likely finding in young children than neurofibromas.

Answer 96

►E Digital myxoid cysts are composed of mucin contained in a cystic structure without a true lining. They may have connections to the joint space, especially in patient’s with osteoarthritis, who are predisposed to developing myxoid cysts. Historically, tuberculosis infection has also been associated with myxoid cysts but there is little current support for this relationship.

Answer 97

►A The defect in congenital erythropoietic porphyria is in the uroporphyrinogen III synthase homozygous defect. It is present after birth with erythrodontia, hyperthrichosis, growth retardation, hemolytic anemia, and increased bone features.

Answer 98

►C In type I cryoglobulinemia, monoclonal IgG or IgM cryoglobulins are found often in association with lymphoma, leukemia, Waldenstrom‟s macroglobulinemia, or multiple myeloma. On histopathology, type I cryoglobulinemia is characterized by the deposition of precipitated amorphous cryoglobulins on the endothelium and throughout the vessel wall. The precipitates stain with PAS stain. An inflammatory infiltrate is typically lacking in contrast to mixed cryoglobulinemia (which shows a leukocytoclastic vascultitis)

Answer 99

►B This patient likely has nephrogenic fibrosing dermopathy (NFD). NFD is an acquired, idiopathic disorder that occurs in renal disease patients. It resembles scleroderma or eosinophilic fasciitis clinically and scleromyxedema histopathologically. Large areas of indurated skin with fibrotic nodules and plaques develop. The extremities are most commonly involved, followed by the trunk. The face, palms and soles are almost never involved. Histopathologically, NFD displays a proliferation of dermal fibroblasts and dendritic cells, thickened collagen bundles, increased elastic fibers, and mucin deposition. Serum protein electrophoresis and immunoelectrophoresis results are negative unlike scleromyxedema, and may be helpful to distinguish the two diseases. NFD is usually a chronic, progressive condition, and favorable responses to medical intervention are anecdotal.

Answer 100

►B Incontinentia pigmenti is an X-linked dominant disorder caused by a mutation in the NEMO gene. Females only present at birth with linear lesions of inflammation and blistering (stage 1), followed by hyperkeratotic verrucous areas (stage 2), hyperpigmentation (stage 3), and then atrophy (stage 4). Systemic findings include psychomotor retardation, microcephaly, seizures, cerebellar ataxia, coloboma, and retinal detachment.

Answer 101

►B Cutaneous manifestation associated with hepatitis C include necrolytic acral erythema, porphyria cutanea tarda, lichen planus, polyarteritis nodosa and mixed cryoglobulinemia. Mixed cryoglobulinemias is a systemic vasculitis with variable manifestations including palpable purpura, arthralgias and weakness. c

Answer 102

►B PCT and HEP are associated with elevated isocoproporphyrins in the stool. Congenital erythropoietic porphyria, hereditary coproporphyria is associated with increased coproporphyria in the stool, and elevated stool proporphyria is seen in variegate porphyria.

Answer 103

►A Fabry's disease is an x-linked recessive disorder characterized by angiokeratomas in a bathing trunk distribution, hypohidrosis, corneal opacities, and acral paresthesias. The diagnosis is confirmed by decreased levels of alph-galactosidase in white blood cells, serum, and fibroblasts. Renal failure is due to accumulation of ceramide trihexoside aka Globotriaosylceramide.

Answer 104

►E All of the statements regarding dermatomyositis are true except for statement E. Elevated muscle enzymes are found in dermatomyositis, but elevated CPK is more specific than aldolase. Diagnosis is also established with muscle biopsy showing evidence of inflammation and abnormal EMG.

Answer 105

►A In patients with mixed cryoglobulinemia, the most likely laboratory abnormality among the options listed is an elevated rheumatoid factor.

Answer 106

►D Eruptive xanthomata appear as erythematous to yellow papule, from1 to 4mm in diameter, generally distributed over the extensor arms, hands, and buttocks. They are present in response to either primary or secondary hypertriglyceridemia. Primary causes are discussed below. Secondary causes include obesity, diabetes, excessive alcohol consumption, estrogens, and systemic retinoids. Type I hyperlipidemia is caused by lipoprotein lipase deficiency and patients have elevated levels of triglycerides (TG) and chylomicrons (chylo). Type I may b e associated with eruptive xanthomata, lipemia retinalis, abdominal pain, pancreatitis, and hepatosplenomegaly. Type IIA is heterozygous for apolipoprotein B deficiency, and results in increased low-density lipoproteins (LDL). Patients may show tendinous or tuberous xanthomata and are at high risk for coronary artery disease (CAD) and stroke. Type IIB is homozygous for apolipoprotein B deficiency and patients have elevated LDL, very low-density lipoprotein (VLDL) and TG. Intertriginous and tuberous xanthomata in addition to advanced atherosclerosis, CAD and stroke at an early age are associated with type IIB. Type III is caused by apolipoprotein E deficiency resulting in elevated intermediate-density lipoproteins (IDL) and TG, and displays palmar/plantar, tendinous and tuberous xanthomata. This disease is associated with diabetes, gout, CAD and stroke. Type IV disease is characterized by increased TG and VLDL and patients may have eruptive xanthomata along with CAD, diabetes and stroke. Type V is caused by an apolipoprotein C2 defect resulting in increased TG, chylo, and VLDL. Eruptive xanthomata, diabetes, hepatosplenomegaly, lipemia retinalis and pancreatitis are associated with type V.

Answer 107

►A Type I is composed of monoclonal immunoglobulins.

Answer 108

►D MEN Type I is also known as Wermer's Syndrome. MEN Type IIA is also known as Sipple's Syndrome. Mucosal neuromas are seen in association with MEN Type IIB. Statement D is correct. Patients with MEN Type IIB are at increased risk for developing medullary thyroid carcinoma.

Answer 109

►D Chronic kidney disease is associated with perforating disorders. These disorder are characterized by pruritus and a biopsy revealing collagen and inflammatory cells broaching the epidermis. The other disorders are not closely associated with perforating diseases.

Answer 110

►B The urine in a patient with carcinoid syndrome features high levels of 5 -hydroxyindolacetic acid and changes color to purple upon addition of nitrosonaphthol. Elevated 24-hour urine norepinephrine or vanilylmandelic acid are seen in pheochromocytoma. Mastocytosis features high levels of tryptase.

Answer 111

►B Malignant acanthosis nigricans usually presents with sudden onset and is rapidly progressive. It may be associated with diffuse keratodermas of the palms and soles or eruptive seborrheic keratoses.

Answer 112

►C Birt-Hogg-Dube is an autosomal dominant condition characterized by trichodiscomas, fibroepilethial polyps and fibrofolliculomas.

Answer 113

►E Several studies have indicated that bilateral diagonal earlobe creases (known as “Frank‟s sign”) may serve as a clinical marker for underl ying coronary artery disease independent of age, particularly in persons younger than 40 years old.

Answer 114

►A There are may cutaneous manifestations of end-stage renal disease. Chronic anemia can cause skin pallor. Deposition of carotenoids can give the skin a yellowish hue. Photo-distributed hyperpigmentation and ecchymoses are also commonly seen. The most common cutaneous manifestation, however, is pruritus. Other cutaneous findings include metastatic calcification, acquired perforating dermatosis, and nephrogenic systemic fibrosis.

Answer 115

►C Laboratory abnormalities of HCV include an elevation of liver enzymes, positive rheumatoid factor (70-90%), and DEPRESSED C3 levels. Classical clinical presentation includes palpable purpura, arthralgias, and glomerulonephritis. Livedo reticularis, hemorrhagic bullae, acrocyanosis, and urticarial plaques can also be found.

Answer 116

►B Metastases to the skin from a thyroid malignancy are rare, but most reported cases occur with papillary adenocarcinoma.

Answer 117

►D Wegener”s granulomatosis is a necrotizing granulomatous disorder that most commonly affects the upper and lower respiratory tracts, kidneys, and eye. Cytoplasmic pattern ant ineutrophil cytoplasmic autoantibody (anti -proteinase-3) is often positive in this disease. Churg-Strauss is associated with a positive p-ANCA. c

Answer 118

►C HEP results from deficient, but not absent, activity of uroporphyrinogen decarboxylase (UROD). HEP is the recessive form of familial PCT. It manifests during infancy or early childhood as photosensitivity, skin fragility in sun-exposed areas, pink urine, erythrodontia, and hypertrichosis.

Answer 119

►A Acanthosis Nigricans can be associated with obesity, insulin resistance, Crouzon”s syndrome, congenital lipodystrophy, and internal malignancy. 90% of related malignancies are tumors within the abdominal cavity. Adenocarcinoma of the stomach is the most common. Malignancy related acanthosis nigricans often occurs in the setting of weight loss, helping distinguish it from other associated diseases.

Answer 120

►B Calciphylaxis is a rare, life threatening disorder that is associated with end stage renal disease. Clinically, patients develop a livedoid purpura and enlarging, tender, indurated subcutaneous plaque typically on the legs or abdomen. These plaques are subject to ischemia, skin necrosis, and secondary infection, sepsis, and death. Histologic examination of calciphylaxis is characterized by the triad of small vessel mural calcification, extravascular calcification, and vascular thrombosis. It appears that vascular mural calcification is an early and essential process in the development of calciphylaxis.

Answer 121

►B This picture demonstrates a shagreen patch in a patient with Tuberous sclerosis. A complication occurring in female patients of child-bearing age is pulmonary lymphangioleiomyoma.

Answer 122

►E A homozygous defect in uroporphyrinogen III synthase in a cause of congenital erythropoietic porphyria, not porphyria cutanea tarda (PCT). PCT may be caused by sporadic or familial deficiency in uroporphyrinogen decarboxylase, or by any of the other causes listed above.

Answer 123

►D Nephrogenic fibrosing dermopathy has an indolent course and treatment is usually not satisfactory. It is not associated with a paraproteinemia or peripheral eosinophilia. Some patients have been reported to have antiphospholipid antibodies. Histopathology demonstrates a minimal to slight increase in dermal mucin.

Answer 124

►E Patients with acute intermittent porphyria have a deficiency in porphobilinogen deaminase. Attacks are precipitated by barbiturates, estrogen, griseofulvin, and sulfonamides. Only 10% of those with genetic defect develop the disease but all at risk for primary liver cancer.

Answer 125

►A This patient has Birt-Hogg-Dube syndrome, an autosomal dominant defect of the BHD gene that encodes folliculin. This syndrome is characterized by the development of trichodiscomas, fibrofolliculomas, and acrochordons starting around age 30. The patients are also at risk for the development of spontaneous pneumothorax and renal cell carcinoma.

Answer 126

►C The organism that causes erosio interdigitalis blastomycetica is candida albicans.

Answer 127

►E The most common site of carcinoid tumor is the ileum. Clinical symptoms of episodic flush ing, abdominal pain, diarrhea, wheezing, and a pellagra-like dermatosis (due to shunting of tryptophan to serotonin) etc present with metastases to the liver. In a report from the SEER database of 11,427 carcinoid cases treated between 1973 and 1997, the majority were located in the gastrointestinal (GI) tract (55 percent) and bronchopulmonary system (30 percent). Within the GI tract, most carcinoids arose in the small intestine (45 percent, most commonly in the ileum), followed by rectum (20 percent), appendix (16 percent), colon (11 percent), and stomach (7 percent)

Answer 128

►A Crohn’s disease (CD) and ulcerative colitis (UC) may both have gastrointestinal tract (GIT) and cutaneous manifestations. CD lesions can involve any area of the GIT (from the lips to the anus), with patchy disease normally present, whereas UC is limited to the colon and rectum and tends to be continuous. Oral disease, fissures and fistulae, metastatic disease to the skin, and polyarteritis nodosa are more commonly associated with CD. Conversely, erythema nodosum, pyoderma gangrenosum and pyoderma vegetans tend to be more commonly associated with UC.

Answer 129

►A This patient has developed multicentric reticulohistiocytosis. Histopathology of the skin lesions will display multinucleated oncocytic giant cells with eosinophilic ground glass cytoplasm. Half of these patients will develop a mutilating arthritis. 20-25% of patients with multicentric reticulohistiocytosis will develop an associated malignancy. The malignancy is usually a carcinoma, but there is no predominant type. c

Answer 130

►B Sickle cell anemia should be considered most likely in any young African American with spontaneous leg ulcers. The ulcers are more common in people with severe anemia.

Answer 131

►C Erythropoietic Protoporphyria (EPP) is characterized by a burning sensation experienced immediately upon photoexposure. Biopsy reveals PAS-positive hyalinization of the superficial dermal vessel walls. This disorder is due to ferrochelatase deficiency. Excess porphyrins are deposited in the liver, which may become cirrhotic.

Cutaneous Manifestations of Systemic Disease Flashcards

(155 cards)