Oral-Cutaneous

Manifestations of Gastrointestinal
and Liver Disease
Oral manifestation of gastrointestinal diseases
 Common oral manifestations of gastrointestinal and systemic diseases
 Gastrointestinal disorders and oral manifestations
 Miscellaneous -Drug-induced oral toxicity
Skin lesions associated with gastrointestinal and liver diseases
 Inherited disorders ,Acquired disorders
 Cutaneous signs of IBD
 Cutaneous signs of liver and pancreatic disease
Common oral manifestations of gastrointestinal and
systemic diseases
Altered taste
 Total aguesia, a total inability to detect
qualities of taste (sweet, salt,bitter, or
sour)
 Partial ageusia - ability to detect some
of but not all the qualitative taste
sensations
 Hypogeusia -with decreased sensitivity to
taste sensation; and
 Dysgeusia - with distortion in the
perception of taste
 Disorders of taste sensation occur due to
conditions that interfere with:
 Transport /sensory loss/neural loss
Transport gustatory loss
access of the tastant to the receptors in
the taste bud
 Drugs: carbamazepine, phenytoin,
nifedipine, diltiazem, glipizide,
losartan, protease inhibitors, ACEI
/ARBs, ampicillin, acyclovir,
terbinafine, doxazosin, gemfibrozil,
simvastatin
 Heavy metal ingestion
 Radiation therapy
 Sjögren syndrome
 Xerostomia
Sensory gustatory loss Central neural gustatory loss
Injury to receptor cells damage to gustatory central
 Candida pathways.
 Radiation therapy  Diabetes
 Herpes infection  Polyneuropathies (lupus,
 Ageing amyloidosis, porphyria)
 Oral neoplasms
 Pemphigus
 Drugs: antithyroid drugs and
antineoplastic drugs
 Local trauma (dental procedures)
Burning mouth
 Burning, tingling, or scalding
sensation in the mouth without any
overt sign of an oral disease.
 It commonly affects women in the
perimenopausal age group and
 commonly affects the tip or
anterior two-thirds of the tongue.
Causes
 Sprue (celiac and tropical)
 Iron deficiency anemia
 Malabsorption
 Niacin deficiency
 Pernicious anemia
 Carcinoid syndrome
Recurrent aphthous stomatitis
 Minor aphthous ulcers - recurrent,  Crohn’s disease Ulcerative colitis
well-defined, small, painful ulcers  Sprue
that heal in 10 to 14 days without  Iron deficiency anemia
scarring.
 Behçet’s disease
 Major recurrent aphthous stomatitis  Malabsorption
lesions are larger (greater than 5
 Acrodermatitis enteropathica
mm), can last for 6 weeks or
longer, and frequently scar.  Amyloidosis
 Pernicious anemia
 Herpetiform ulcers, which present
as multiple small clusters of  Pyridoxine, B-6, folate deficiencies
pinpoint lesions that can coalesce  Steroid use
to form large irregular ulcers and  GERD
last 7 to 10 days.
 Graft-versus-host disease
 Bulimia
 AIDS
Apthous ulcers usually heal in 7–14 days without scarring. Treatment is largely aimed
at symptomatic relief, promotion of healing, and reducing recurrence.
 Topical corticosteroids, such as hydrocortisone 1% topical gel or ointment (three to
four times a day)
 Topical antimicrobial agents may be required for secondary infections.
 severe recurrent aphthous stomatitis -oral/intralesional corticosteroids, antitumor
necrosis factor-α (anti-TNF-α) agents, and calcineurin inhibitors (such as
cyclosporine)
 Chemical cautery with 0.5%–1% silver nitrate
 Colchicine
 Dapsone
 Recalcitrant cases- interferon-α (IFN-α)
Glossitis Angular cheilitis
Inflammatory condition of the tongue - atrophy of
the filiform papillae resulting in a smooth,
featureless, and erythematous appearance. Inflammation of the angles of the lips

 Alcoholism  Crohn’s disease

 Crohn’s disease

 Alcoholism
Sprue
 Iron deficiency anemia  Sprue
 Pernicious anemia  Iron deficiency anemia
 Malabsorption

 Malabsorption
Carcinoid syndrome
 Kwashiorkor  Acrodermatitis enteropathica
 Amyloidosis
 Plummer–Vinson syndrome
 Pyridoxine (B-6) ,niacin (B-2), folate deficiencies

 Folate, B-6, B-2 deficiencies
Plummer–Vinson syndrome
 Cowden disease
Oral pigmentation

 Location on the palate increases Causes

the rate of suspicion of melanoma
and usually requires a biopsy or
long-term follow-up.
 ABCDE (asymmetry, border
irregularity, color variegation, and
diameter >6 mm, evolving)
 In case of any doubt a biopsy
should be taken. Rapidly growing
or symptomatic pigmented lesions
should always be biopsied.
 Peutz–Jeghers syndrome
 Addison disease
 Acanthosis nigricans
 Pseudoxanthoma elasticum
 Scurvy
 GERD
 Lead poisoning
 Gardner syndrome
Vascular lesions / bleeding syndromes

 Hereditary hemorrhagic telangiectasia

 Blue rubber bleb nevus
 Scleroderma
 Kaposi sarcoma
 Pseudoxanthoma elasticum
Gastroesophageal reflux disease

 In health, esophageal clearance prevents acid from reaching the oropharynx.

 Esophageal clearance is achieved by two mechanisms: peristalsis and the
buffering action of calcium and phosphate ions present in saliva that
neutralizes the acid.
 Chronic exposure of the oral cavity to gastric acid has a variety of effects.
 Dental erosions, defined as the loss of tooth substance leading to a hard
“dished-out” area with a smooth base.
 Burning mouth sensation
 Halitosis
 Laryngitis
Inflammatory bowel disease

 Aphthous ulcers may occur before or after the diagnosis of IBD

 prevalence of oral manifestations among adults with Crohn’s disease ranges
from 0.5% to 9%
 Characteristic of Crohn’s disease include swelling of the lips, buccal mucosal
edema or cobblestoning, deep linear ulceration, mucosal tags, and
mucogingivitis
 Noncaseating granulomas have been detected in the majority of biopsies of
oral lesions in patients with Crohn’s disease.
 Principles of treatment for oral lesions are similar to those for Crohn’s disease
affecting the intestine.
 Topical steroids
 systemic corticosteroids and/or immunosuppressants such as azathioprine.
 Thalidomide-for refractory cases
 Correction of nutritional deficiencies can lead to improvement in some of the
oral lesions
 and specific treatment for superimposed infection (e.g., due to Candida) may
also be required.
 Oral lesions in ulcerative colitis include irregular-shaped ulcers and
nonspecific gingivitis.
 Histological examination of biopsies shows features of acute and chronic
inflammation, without granulomas
 Pyostomatitis vegetans- labial and buccal mucosae are affected with pustular
lesions, cobblestone pattern, ulceration, and hemorrhagic crusting.
 It is considered by some to be the mucosal analogue to cutaneous pyoderma
gangrenosum and
 histological features of biopsy include acanthosis and neutrophilic
microabscesses.
 Treatment – Treat underlying disease , dapsone.
Celiac disease

 Dental enamel defects (10% to 96% )and aphthous ulcers (4% to 41%) are the
most common.
 Other oral manifestations include delayed eruption, cheilitis, oral lichen
planus, and atrophic glossitis.
 The defects include hypomineralization and hypoplasia, resulting in defects in
color and structure of the enamel manifest as grooves, pits, or change in
shape of tooth in severe cases.
 Proposed hypotheses include hypocalcemia from malabsorption and
stimulation of naïve lymphocytes by gluten in the oral cavity, leading to
immune mediated damage.
Behcet’s disease

 Behcet’s disease is a multisystem inflammatory vasculitis - relapsing episodes

of oral aphthous ulcers, genital ulcers, cutaneous and ocular lesions.
 Gastrointestinal involvement - ileocolonic disease with either small-vessel
vasculitis that leads to recurrent mucosal aphthoid, or deep ulceration along
the antimesenteric border with a tendency to perforate and recur at the
anastomotic site following surgery.
 Less commonly, Behcet’s disease presents as a manifestation of large-vessel
mesenteric vasculitis with associated bowel ischemia/infarction.
 Rarely, the upper GI tract is involved , presents as linear ulcers in the
esophagus and resistant recalcitrant peptic like ulcers in the stomach and
duodenum with complications such as gastric outlet obstruction or a Dieulafoy
lesion with ulcer.
 Almost all patients with Behcet’s disease develop frequent oral ulcers that
are indistinguishable from apthous ulcers.
 oral ulcers are commonly small aphthoid in nature (minor ulcers), less than 10
mm in diameter.
 Less commonly, they appear as herpetiform lesions or giant ulcers.
 most commonly involved sites are gingival and buccal mucosa, tongue, and
lips, although ulcers can also appear in the soft and hard palate, pharynx, and
tonsils.
 Lesions are painful ,usually heal in 1–3 weeks without scarring, with the
exception of major ulcers.
 Oral ulcers usually present early in the disease process and are usually the
last to disappear during remission.
 oral lesions do not respond to topical treatments
 Colchicine -effects on oral ulceration are variable
 systemic glucocorticoids,
 azathioprine,
 anti-TNF agents such as etanercept , infliximab, and adalimumab ,
cyclosporine ,
 IFN-α
 thalidomide
Hereditary hemorrhagic telangiectasia

 also known as Osler– Weber–Rendu syndrome,

 autosomal dominant disorder characterized by telangiectasias of the skin and
oral mucosa and arteriovenous malformations in the brain, lung, liver, and
gastrointestinal tract.
 Type 1 (HHT1) in which there is mutation of the endoglin gene on
chromosome 9 with pulmonary involvement;
 Type 2 (HHT2) with a mutation in the activin receptor-like kinase-1 (ALK1)
gene, milder form
 bleeding episodes occur due to fragility of the capillary walls resulting from
defective proteins produced by the gene mutations
 HHT affects the GI tract in at least 33% of the cases, commonly presenting as
chronic iron deficiency anemia or occult GI bleeding
Curacao criteria: 3 or more
 Telangiectasia on the face, hands, and
oral cavity;
 recurrent epistaxis;
 arteriovenous malformations with
visceral involvement;
 and family history.
Treatment
 Iron supplementation
 Blood transfusion
 Tranexamic acid
 Tamoxifen
Blue rubber bleb nevus syndrome

 venous malformations affecting the

oral cavity, skin, GI tract, and viscera.
 Patients commonly present with
symptoms of GI bleeding or rarely
with abdominal pain from intusseption
 Blebs are noticeable at birth and may
increase in size and number over
time.
 The lesions are compressible, fleshy,
and rubbery in consistency, nontender
to mildly tender and the skin over
lesions may exhibit hyperhidrosis.
Treatment
 Iron therapy and transfusions
 corticosteroids, vincristine, IFN-α, sirolimus, and octreotide
 Endoscopic treatment of lesions with histoacryl glue injection , argon plasma
Coagulation , mucosal resection/polypectomy, and endoscopic band ligation
 Most patients have a normal life span.
 Following definitive therapy of lesions, formation of new lesions is known to
occur, warranting regular endoscopic surveillance.
Gardner syndrome

 variant of familial adenomatosis polyposis (FAP), which is characterized by

 colonic polyposis ,
 osteomas (most commonly in the skull and the mandible),
 dental abnormalities, (odontoma and multiple unerupted supernumerary and
permanent teeth )and
 soft tissue tumors such as desmoid and epidermoid cysts
 The dental abnormalities and osteomas of the mandible precede the onset of
colonic polyposis, which may enable early diagnosis.
 mutation in the adenomatous polyposis coli (APC) gene.The number of colonic
polyps is related to the locus of the mutation in the APC gene and
 there is some correlation of bone, cutaneous, and desmoid tumor occurrence with
location of mutation in the distal or 3′ portion of the APC gene
Puetz–Jeghers syndrome

 characterized by mucocutaneous
pigmentations, gastrointestinal
polyposis, and an increased risk of
gastrointestinal and extraintestinal
cancer
 Diagnosis- based on clinicopathological
criteria of histological confirmation of
GI hamartomatous polyps and two of
the following features:
(1) small bowel polyposis;
(2) family history of PJS; and
(3) pigmented macules in the perioral
area, lips ,fingers, or toes
 The condition is suspected when the patient presents with surgical
emergencies such as intussusception or GI bleeding, and noted to have
perioral pigmentation.
 The pigmentation appears as freckles of varying size and may develop at any
age but commonly manifests during infancy and early childhood, with
tendency to fade after puberty.
 Pigmentation, which consists of melanin in the subepithelial region, occurs
universally in the lips in more than 95% of cases and in the buccal cavity in
85%.
 Hamartomatous polyps occur anywhere in the GI tract from the stomach to
the rectum but are mostly found in the jejunum and their numbers vary from
a few to a hundred.
Drug-induced oral toxicity

 Mucositis, affecting the oropharyngeal mucosa, may occur in 35%–40% of

patients that receive drugs for treatment of cancer ( bleomycin, 5-flurouracil,
methotrexate, etoposide, doxorubicin, sorafenib, and mTOR inhibitors)
 The mucositis is often a short-lived and self-limiting condition.
 Clinical presentation can be wide, ranging from burning sensation of the oral
cavity to severe exfoliative inflammation, erythema, and desquamation
resulting in shallow coalescing ulcers to pseudomembranes.
 The peak occurrence is about 5–7 days after chemotherapy, with resolution
over the subsequent 10–14 days.
Skin lesions associated with
gastrointestinal and
liver diseases
Introduction

 Many diseases of the gastrointestinal (GI) tract can have characteristic

manifestations arising in the skin, hair, and nails.
 The integumentary and GI systems share epithelial and connective tissue
structural elements that may partly contribute to direct disease
manifestations in these two systems.
 Recognition of cutaneous manifestations of GI diseases may help in early
diagnosis, treatment, and in identifying patients at risk for developing cancer.
Acquired disorders

Paraneoplastic and related syndromes

Acrokeratosis paraneoplastica of Bazex
 predominantly acral dermatitis that is highly associated with internal malignancy.
 Men aged 60 and older are most often affected, and
 squamous cell carcinoma of the upper aerodigestive tract accounts for most cases
 erythematous to slightly violaceous scaly plaques on the palms and soles as well as
nail dystrophy.
 Ears and nose involved
 The onset of the rash often precedes the diagnosis of malignancy by an average of
11 months
 The rash of AP typically resolves if the primary tumor is successfully treated.
Acanthosis nigricans
 hyperpigmented velvety or papillomatous plaques of the skin.
 In the syndromic or inherited form, AN is associated with defects in insulin
homeostasis and fibroblast growth factor receptors .
 In the acquired form, AN is usually associated with metabolic disease and
hyperinsulinemia .
 Rarely, acquired AN can be a paraneoplastic phenomenon and is designated
malignant AN.
 Gastric adenocarcinoma is the most commonly associated tumor, followed by
cancer of the uterus, liver, and lung.
 The alterations of the epidermis (i.e., hyperkeratosis and papillomatosis)
seen in AN associated with hyperinsulinemia are thought to arise from the
action of insulin-like growth factor 1 on keratinocytes .
 In malignant AN, the proposed mechanism involves tumor-associated
transforming growth factor-α stimulating epidermal growth factor receptors .
 The hyperpigmented and velvety plaques of AN most frequently involve the
neck, axillae, and groin
 In very early lesions of AN, only hyperpigmentation may be present
 Malignant AN more commonly involves the palms, soles, and mucosal surfaces
and may spare typical sites such as neck and axillae.
 The occurrence of AN in otherwise healthy patients with no signs of metabolic
disorder should raise the specter of malignancy.
Sign of Leser–Trelat
 Abrupt onset of multiple seborrheic keratoses
in a patient with visceral malignancy.
 The most commonly associated malignancy is
adenocarcinoma of the GI tract followed by
adenocarcinoma of the breast
 the validity of this sign is not universally
accepted.
Necrolytic migratory erythema
 erosive intertriginous and periorificial dermatitis, which is recognized as a
cutaneous manifestation of glucagon-secreting islet cell tumors of the
pancreas.
 NME is present in 50%–70% of cases of glucagonoma at the time of initial
presentation .
 NME may also occur in “pseudoglucagonoma syndrome” patients without
glucagonoma but with elevated glucagon levels occurring in malabsorption
disorders or liver disease.
 Clinically, NME presents as a pruritic or painful rash predominating in the
perineum, buttocks, and lower extremities. There is also a striking tendency for
periorificial involvement.
 The rash consists of erythematous annular plaques, which may vesiculate or
blister before becoming crusted and ultimately healing spontaneously.
 The disease is characterized by unpredictable episodes of relapse and remission.
 Skin biopsy-pallor and ballooning degeneration of the upper layers of the
epidermis.
 Management -Treatment of glucagonoma
octreotide and
supplementation of zinc or amino acids
Plummer–Vinson syndrome
 characterized by the triad of postcricoid dysphagia, esophageal webs, and
iron deficiency anemia
 Mucocutaneous signs include koilonychia, glossitis, and angular stomatitis
 Koilonychia - fingernails or toenails are spoon-shaped and brittle.
 Glossitis presents as erythematous plaques of the tongue, sometimes with loss
of fungiform papillae.
 Angular stomatitis (perleche) describes scale, erythema, and fissuring at the
oral commisures.
 significant association of PVS with squamous cell carcinoma of the upper GI
tract, occurring in 3%–15% of patients.
Carcinoid syndrome
 refers to a clinical spectrum of symptoms caused by bioactive peptides
secreted by carcinoid neuroendocrine tumors
 The carcinoid syndrome occurs in less than 10% of affected patients
 classic components –abdominal pain, flushing, diarrhea , and
bronchoconstriction
 Isolated tumors of the bowel may be asymptomatic because of hepatic
metabolism of vasoactive peptides, but primary tumors of the lung or liver
metastases may bypass this metabolic effect and lead to symptoms.
 Neuroendocrine tumors originating in the embryological foregut are said to
produce a bright pink flush while
 those originating in the mid gut produce a cyanotic or violaceous flush
 Over time, flushing leads to signs of rosacea such as rhinophyma,
telangiectases, and an acneiform eruption
 symptoms of carcinoid syndrome may abate with surgical extirpation of the
neuroendocrine tumor.
 Alternative treatments include somatostatin analogues and cytotoxic agents.
Hypertrichosis lanuginosa acquisita
 rare disorder characterized by excessive lanugo hair (long, thin, and
unpigmented with a fine or downy texture)
 lanugo hairs appear suddenly and first on the forehead, ears, and nose. In
severe cases, the lanugo hair growth extends caudally onto the trunk and
extremities.
 HLA can be caused by medications, thyroid disorders, and malignancy.
 In women with HLA, colorectal adenocarcinoma is most common, followed by
cancer of the lung and breast.
 In men, lung cancer is most common, followed by colorectal cancer.
 poor prognosis due to advanced disease at the time of presentation.
Tylosis
 refers to a specific type of palmoplantar keratoderma strongly associated with
esophageal cancer (tylosis-esophageal cancer or Howel–Evans syndrome).
 2 clinical subsets
 Type A represents late-onset disease with a high risk of malignancy;
 Type B represents early-onset disease with a much lower risk of malignancy
 In adulthood, patients develop keratoderma (i.e., thickened yellow plaques) on
the weight bearing aspect of the palms and soles, Follicular hyperkeratosis and
oral leukokeratosis .
 By age 65, over 95% of patients will develop esophageal carcinoma. Cancer
screening by esophageal endoscopy can reveal areas of mucosal hyperkeratosis
and dysplasia
Extramammary Paget disease
 It is a rare cutaneous adenocarcinoma.
 EMP most often occurs on the vulva, scrotum, penis, genitocrural,
and perianal areas.
 EMP usually presents as scaly or crusted nodular plaques, sometimes with erosions
 smaller fraction, approximately 12%, of EMP represents secondary disease and is
associated with underlying visceral malignancy, usually adenocarcinoma
 site of involvement suggests the source of the malignancy .
 groin and/or genital regions -malignancy of the genitourinary system may exist.
 Perianal EMP -rectal adenocarcinoma in 25% of cases
 Treatment is aimed at the underlying malignancy when present.
Cutaneous metastasis of GI cancer
 presents as a painless firm pink nodule or plaque in proximity to the primary
tumor .
 The scalp -common site for distant metastases, due to its high vascularity.
 Invasive adenocarcinoma may obstruct contiguous lymphatics and lead to
induration and erythema ,termed carcinoma erysipeloides.
 GI carcinoma may track along the falciform ligament or other embryological
remnants and present at the umbilicus as a painless dermal nodule known as
Sister Mary Joseph’s node.
 usually occurs after the primary tumor has been diagnosed
 Histopathology - goblet cells and intraglandular neutrophils
Cutaneous signs of inflammatory bowel
disease
Specific signs of inflammatory bowel disease
Mucocutaneous Crohn’s disease
 Specific signs of skin involvement by CD include fissures, fistulae, mucosal
cobblestoning, and metastatic Crohn’s disease
 Perianal inflammation, along with perifistular and peristomal inflammation, is
thought to represent the most common cutaneous manifestation of CD .
 one-third of patients with CD will have perianal inflammation .
 Perianal fistulae are most common in patients with colonic or ileocolonic
inflammation.
 Metastatic CD occurs in skin sites
discontiguous to intestinal
inflammation
 present as ulcerated nodules or
plaques affecting the arms, legs,
genitals, or face.
 The onset of metastatic CD
precedes GI manifestations of CD
 multiple, edematous, and
circumanal lesions
 In the oral mucosa, CD cause ulcerative lesions that are herpetiform or linear
 When linear ulcerations intersect in an edematous mucosa, a cobblestone
appearance develops.
 Dense granulomatous inflammation impart hardness to the lips. Such
involvement of the upper lip can cause swelling called “beaking”(i.e., the
protrusion of the swollen upper lip outward beyond the patient’s lower lip).
Nonspecific, reactive signs of inflammatory
bowel disease

Pyoderma gangrenosum
 inflammatory, ulcerative disorder of the skin.
 The term pyoderma represents a sort of misnomer as infection is not
implicated in the pathogenesis of PG.
 Ulcer –due to neutrophil dysfunction and an abnormal inflammatory response
to nonspecific stimuli
 In 25%–50% of cases, PG is idiopathic
 PG is rare overall in the IBD population, occurring in less than 2% of patients .
 However, about 20%–30% of patients with PG will have concomitant IBD.
 Other systemic diseases associated with PG include rheumatoid arthritis,
paraproteinemia, chronic active hepatitis, and haematological malignancy.
 PG begins as a painful subcutaneous
papule or nodule on which a pustule
may supervene.
 The nodule expands and eventually
degenerates, creating a necrotic
ulcer with an exudative and
hemorrhagic base
 Dx –Exclusion of others such as
infection, cutaneous malignancy,
vasculitis, and vasculopathy.
 Wound care ,Oral corticosteroids ,
Immunosuppressive therapy and
tumor necrosis factor-α blockers
Pyostomatitis vegetans
 pustular and erosive disorder of the oral mucosa.
 multiple pustules on an erythematous and edematous base
 epithelial hyperplasia imparts a vegetating appearance -“snail-tracking”
appearance.
 Concomitant involvement of the skin with pustules and vegetative plaques is
called pyoderma vegetans.
 Despite extensive involvement, pain is not always present.
 Eosinophils are a major component of the inflammatory infiltrate on
histopathology, and over 90% of patients have evidence of peripheral
eosinophilia
Erythema nodosum
 Inflammatory panniculitis that most commonly affects the pretibial regions
 Most common cutaneous manifestation of IBD.
 It is more often associated with CD (2-7%) than with ulcerative colitis (0.9-
4%).
 EN preferentially affects women
 Hypersensitivity mediated by immune complex deposition is thought to drive
the pathogenesis of EN, but the exact mechanism is unknown.
 Clinically, EN manifests as an abrupt onset of discrete tender subcutaneous
nodules on the anterior aspect of the lower extremities. Rarely, the upper
extremities or face are involved
 Systemic symptoms such as fever or arthralgia may be present.
 Episodes tend to resolve after 3 to 6 weeks but may last much longer.
 Lesions do not ulcerate and heal without scarring.
 Diagnosis HPE -septal panniculitis.
 Treatment of underlying IBD typically improves EN.
 NSAIDs can help relieve symptoms, and
 saturated solution of potassium iodide in persistent cases.
Aphthous ulcers
 Recurrent aphthae occur more commonly in patients with IBD. 10% of patients
with CD and 4% of patients with ulcerative colitis
 Typically small (i.e., 2–4 mm2), round or ovoid, with a clean gray or yellow
base. These lesions are designated as “minor” ulcers.
 They can occur anywhere in the mouth, but are uncommon on the palate and
dorsal aspect of the tongue.
 They tend to heal spontaneously after about 1 week.
Polyarteritis nodosa
 Inflammatory vasculitis of small to medium-sized arteries.
 Systemic form of PAN affects the skin, kidney, liver, gastrointestinal tract, and
heart. (Hep B >C)
 The cutaneous form of PAN (CPAN) predominates in the skin, although arthralgias
and neuropathy may be present (CD > UC)
 The exact pathogenesis of PAN is unknown, but immune-complex-mediated
vasculitis plays an important role.
 CPAN present with painful erythematous nodules or plaques on the lower
extremities. Overlying livedo reticularis is an important clue to the diagnosis.
The plaques may ulcerate;
 CPAN follows a relapsing and remitting, but generally uncomplicated, course
Sweet syndrome
 acute febrile neutrophilic dermatosis characterized by the abrupt onset of
erythematous, edematous plaques and nodules (upper limbs and trunk)as well
as systemic signs of fever and neutrophilia.
 The disease may follow an URTI or occur in association with pregnancy or
systemic diseases, including IBD, haematologic malignancy (especially AML).
 10% of patients with Sweet syndrome had IBD (CD>UC) ,F predominant
 Biopsy of lesions reveals a inflammatory infiltrate of neutrophils in the
dermis, accompanied by variable degrees of edema in the papillary dermis
 Systemic corticosteroids, treat underlying disorder
Cutaneous Manifestations of
Liver Diseases
Palmar erythema
 characterized by a slightly warm but otherwise asymptomatic redness of the
palms.
 The hypothenar and thenar eminences are most often affected; rarely the
entire palm is involved.
 The red hue of PE is fixed rather than transient, and
 there is not a mottled appearance as might be seen in physiological
hyperemia.
 A number of medical conditions have been associated with PE, including
pregnancy, liver disease, thyroid disease, diabetes mellitus, and connective
tissue diseases
Spider nevus (spider telangiectasia, spider angioma, nevus araneus)
 small, benign vascular proliferation associated with chronic liver disease that
consists of a central arteriole from which radiate several tapering, finer
vessels.
 most commonly distributed in the vascular territory of the superior venacava
(i.e. the head, neck, and upper trunk).
 Also develop during pregnancy, oral contraceptives use, and in some healthy
individuals.
 pathogenesis is thought to relate to increased estrogens and circulating
angiogenic factors.
 Like PE, the frequency of spider nevi in chronic liver disease increases with
increasing severity of liver fibrosis.
Terry’s nails
 characterized by a uniform white
color of the majority of the nail
bed, save for a distal transverse
band of pink 1 to 2 mm in width
just proximal to the onychodermal
band.
 also occurs in patients with
congestive heart failure, chronic
renal failure, hematological
disease, advancing age, or normal
health.
Pruritus and prurigo nodularis
 sensation of itch, is common in patients with chronic liver disease, particularly
those with cholestasis
 Bile acids accumulate in the skin of patients with cholestatic liver diseases.
 Endogenous opioid levels and progesterone metabolites.
 Autotaxin is a lysophospholipase enzyme that produces lysophosphatidic acid,
a proposed pruritogen.
 Pruritus may precede the diagnosis of an associated cholestatic liver disease in
up to 75% of patients .
 The pruritus of cholestasis is often described as a “pins and needles” sensation
which is not improved by scratching . Itching is worse at night and with heat.
 Prurigo nodularis is a clinical
manifestation of chronic pruritus
and scratching.
 These lesions are firm, dome-
shaped papules or nodules that are
often hyperpigmented ,lichenified
(i.e., thick dry skin with increased
skin fold markings).
Cutaneous signs of hepatitis C virus
infection
Porphyria cutanea tarda
 due to decreased activity of
uroporphyrinogen decarboxylase
 hepatitis C virus (HCV) infection
(~56%),
 hereditary hemochromatosis (~73%)
 alcohol abuse,
 human immunodeficiency virus
infection, and
 estrogen therapy.
 TOC –Phlebotomy ,HCQ ,Iron chelation
Lichen planus
 chronic inflammatory
papulosquamous disease of the skin
and mucous membranes
 Oral Lesions bilateral and
symmetric. whitish reticulate
patches on the buccal mucosa.
 Histopathology-band-like infiltrate
of lymphocytes obscuring the
epidermal BM,
 hypergranulosis of the epidermis.
Necrolytic acral erythema
 Scaly erythematous well-demarcated plaques
 dorsum of the hands and feet, knees, and extensor aspect of the lower
extremities
 dark red or violaceous hue. scalp spared
 Histology- hyperkeratosis and pallor or necrosis of keratinocytes
 Treatment of the underlying HCV infection -results in remission
Cryoglobulinemia
 Cryoglobulins are circulating immunoglobulins that reversibly precipitate at
low temperatures.
 Cryoglobulinemia is found in 40% of patients with HCV infection.
 Majority (65%) have type II mixed cryoglobulins (polyclonal IgG and
Monoclonal IgM), remainder have type III mixed cryoglobulins.
 Precipitation of cryoglobulins in small blood vessels leads to immunologically
mediated vasculitis.
 Palpable purpura
 Chronic leg ulcers typically located superior to the malleoli are seen
Other cutaneous signs of hepatitis

Gianotti–Crosti syndrome
 Papular acrodermatitis of childhood
 Etiology – HBV ,EBV
 Rash -monomorphous pink to brown papules or vesicles distributed
symmetrically on acral sites,face & the ears.
 resolves spontaneously without scarring within 10 to 60 days
Leukocytoclastic vasculitis
 deposition of circulating immune complexes in postcapillary venules followed
by complement-mediated injury of the cutaneous vascular plexus.
 Etiology -Idiopathic, infection (HCV >HBV),
 rheumatological diseases, malignancy, and medications.
 Palpable purpura
 Superficial vesicles
Cutaneous manifestations of pancreatic
disease
Pancreatic panniculitis
 Rare complication of acute and chronic pancreatitis ,also in acinar cell
carcinoma
 Pathogenesis -action of pancreatic enzymes, namely lipase and amylase, on
subcutaneous adipose tissue.
 subcutaneous, tender, and ill-defined nodules with a red or red-brown hue
over lower limbs ,trunk.
 Nodules ulcerate oily brown discharge
 pancreatic panniculitis, polyarthritis, and peripheral eosinophilia -Schmid’s
triad
Cutaneous signs of acute pancreatitis
 seen in 1.2%,suggests more severe disease
 Grey–Turner sign -Ecchymosis of the flank
 Cullen’s sign -periumbilical ecchymosis
 Fox’s sign -ecchymosis inferior to the inguinal ligament
 Bryant’s sign –ecchymosis of scrotum
 Walzel’s sign -acute pancreatitis and livedo reticularis of the abdomen or
chest
Mucocutaneous manifestations of
nutritional deficiencies
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