Gastrointestinal Manifestations of Dermatologic

Disorders

hshields@bidmc.harvard.edu
:Prepared by
.Dr.Mohammad Shaikhani
Assistant professor
Sulaimani University
College of Medicine
.Dept of Medicine

For Derma postgraduate students

 :Introduction
 Primary dermatologic diseases may involve the GIT or systemic
diseases involving the skin, GI tract& liver simultaneously.
 The correct diagnosis relies on the ability of the gastroenterologist
to recognize the underlying dermatologic disorder& include.
 Examples:

 IBD/Hepatitis C/Celiac disease

 Epidermolysis bullosa/Mastocytosis/Hereditary hemorrhagic

telangiectasia/Melanoma
 Epid ermo ly sis Bu llo sa: case
 A 16-year-old girl with a H/O epidermolysis bullosa& recurrent
mouth ulcers presented with chest pains on swallowing &painful
oral lesions.
 An upper endoscopy was performed
 :Epid ermo ly sis Bu llos a
 Is an inherited disorder characterized by the formation of blisters
after minor skin trauma.
 Scarring may result.

 This disorder can affect any epithelialized organ.

 Skin Findings

 Tense, fluid-filled blisters, erosions, crusts form in response to

minimal trauma.
 Scarring frequently occurs.
 :GIT fe ature s
 Poor dentition
 Esophageal strictures.

 Malabsorption

 Severe constipation.

 Anal fissures.

 Trauma from food boluses leads to bullae,ulceration, scarring of

the esophageal mucosa with formation of strictures, more
frequently in the proximal than the distal esophagus
 Dysphagia is common.

 Pyloric atresia associated with the junctional form& carries a

very poor prognosis.
 EB :Pathophysiology
 Mutations of genes encoding proteins located at epidermis/dermis,
junction forming a link from basement membrane to the dermis.
 3 forms are recognized.

 1. Simplex: dominant mutations in genes controlling cytokeratins

5/14/tonofilaments& presents with blisters in the lowermost part
of the keratinocytes.
 2.The junctional form: recessive mutations in the laminin-5 (type
XVII collagen), affecting hemidesmosomes in the dermis or 6/ 4
integrin genes , characterized by blisters in the lamina lucida.
 3. Dystrophic form:dominant or recessive mutations in type VII

 collagen, resulting in blisters beneath the lamina densa&other

organs as esophagus, where these same proteins reside.
 :Manage men t
 Supportive.
 Minimizing trauma with a soft diet, attention to wound care,
adequate nutrition.
 Antireflux measures /PPI may be helpful to minimize eso damage.

 Transplantation of genetically modified epidermal stem cells to

improve the adhesion properties of primary keratinocytes
currently is investigated.
 The risk of mucosal trauma from endoscopic procedures should
be considered before proceeding.
 Esophageal strictures dilated with balloons rather than bougies.
 Mastocytosis: Case
 A 59-year-old woman with recurrent attacks of abdominal pain,
nausea, vomiting& profound dyspnea comes into ER with chest
tightness.
 She had self-administered IM epinephrine without improvement.

 In the ER, she was tachypneic with diffuse wheezes on exam.

 She was placed on solumedrol IV.

 The CXR was negative.

 H/O mast cell activation syndrome.

 Her skin showed patchy erythema on the face / arms.

Masto cyto sis : Case
 Masto cyto sis :derma features
 Urticaria pigmentosa,diffuse cutaneous mastocytosis, solitary
mastocytoma of the skin.
 The yellow-tan macules involve the extremities, trunk, abdomen,
but spare the palms, soles, scalp.
 Biopsy reveals multifocal aggregates of mast cells

 Cutaneous mastocytosis, usually is spontaneously regressive when

it develops in childhood.
 Patients with systemic mastocytosis generally are older &usually
present with infiltration of multiple organs.
 Cutaneous disease is present in only about half of all patients.
 Masto cyto sis :GIT features
 Infiltration of liver causes hepatomegaly, liver dysfunction, ascites
 Histologic features include aggregates of mast cells both in
sinusoids& periportal areas,but fibrosis is uncommon.
 Intestinal involvement associated with nausea, vomiting, abd pain.

 Malabsorption, diarrhea,weight loss, hypoalbuminemia are

prominent in some patients.
 Histamine release, increase gastric acid leading to PUD with a risk
of bleeding/ perforation.
 In systemic mastocytosis, common physical findings include
splenomegaly, lymphadenopathy&bone pain/myalgia secondary to
the infiltration of the musculoskeletal system&BM involvement,
result in anemia& pancytopenia.
 Masto cyto sis : Management
 GI manifestations can be managed with interferon alfa& 2-
chlorodeoxyadenosine.
 The recent identification of kit / PDGFRA mutations have
modified the therapeutic algorithm.
 Although a subset of patients with kit juxtamembrane mutations
(eg, K509I) appear to have a imatinib-responsive disease, the vast
majority with a mutation at codon 816 may be resistant.
 Symptomatic treatment of mast cell mediator release usually is
managed with H1/H2- blockers & cromolyn sodium.
 CSs are reserved for recurrent or refractory symptoms.
 Hereditary Hemorrhagic Telangiectasia
(Osler–Weber–Rendu Disease): Case
 A 68-year-old man with HHT was admitted with a decreasing Hb
 His past history was notable for a partial lung resection of
pulmonary (AVMs)& recent mild CHF.
 He was noted to have telangiectases on the face& chest, a bruit in
the right upper quadrant&dark brown stool positive for blood.
 A CXR revealed large AVMs in the left lower lobe, as did the
chest&abdominal CT) scans which also showed hepatic AVMs.
 The patient underwent an upper endoscopy; bleeding medium-
sized AVMs were seen in the duodenum&jejunum.
 Hereditary Hemorrhagic Telangiectasia
(Osler–Weber–Rendu Disease):
 HHT, a multisystem disease, genetically mediated disorder of
fibrovascular tissue.
 The definitive diagnosis based on the Curaçao criteria, require
presence of at least 3 of the following 4 clinical features:
 (1) Spontaneous, recurrent epistaxis.

 (2) Telangiectases at characteristic sites as lips, oral cavity,

fingers, or nose
 (3) visceral lesions as cerebral or spinal AVMs, GI tract
telangiectasias, pulmonary AVMs, hepatic AVMs
 (4) A family history of HHT in a first-degree relative.
 Hereditary Hemorrhagic Telangiectasia
(Osler–Weber–Rendu Disease):Skin
 Telangiectases that may be punctate, linear, or spider-like on the
upper body& in the mouth, including the tongue, nasal mucus
membranes&nail beds.
 They characteristically blanch partly with pressure but do not
pulsate.
 Hereditary Hemorrhagic Telangiectasia
(Osler–Weber–Rendu Disease):GIT
 HHT should be considered in any patient with bleeding from the
GI tract or with anemia& a history of epistaxis.
 In any patient with bleeding, the gastroenterologist should
examine the lips& tongue for telangiectases.
 Telangiectases involve GITorgans in 11%–25%, with the stomach
&small bowel being the source of bleeding more than the colon.
 The manifestations of bleeding, as IDA, generally begin in the fifth
decade.
 The gastroenterologist also should recognize the variety of clinical
manifestations that occur secondary to hepatic AVMs, including
high-output CHF, portal hypertension& biliary ischemia.
 Hereditary Hemorrhagic Telangiectasia
(Osler–Weber–Rendu Disease):GIT
 The exact clinical manifestation depends on which vascular beds
(hepatic artery, hepatic vein, portal vein) the predominant
shunting is between (ie,hepatic artery to hepatic vein leads to high-
output heart failure).
 Juvenile polyposis may occur in patients with HHT& vice versa.

 Patients with early onset GI bleeding should be screened for

juvenile polyps given their malignant potential.
 Hereditary Hemorrhagic Telangiectasia
(Osler–Weber–Rendu Disease):GIT
 The most common symptom, epistaxis, clinically becomes
prominent in puberty.
 Recurrent epistaxis is managed conservatively with nasal ointment
, tamponade, but local treatments including endonasal laser
coagulation or argon plasma coagulation & septodermoplasty.
 Finally, antifibrinolytics as aminocaproic acid/ tranexamic acid
have met with some success.
 Hereditary Hemorrhagic Telangiectasia
(Osler–Weber–Rendu Disease):GIT
 GI involvement: there is an inverse relationship between the
number of telangiectatic lesions in the gut&the hematocrit.
 Capsule endoscopy has shown a 56% prevalence of telangiectases
in the small bowel.
 Because the bleeding generally is limited to slow oozing, the
primary management should be frequent checks of the Hb on a
weekly basis to identify patients who need transfusions if oral or
intravenous iron is not sufficient to increase Hb to > 10 g/dL
 Estrogen/progesterone should be tried

 Argon plasma&embolization.
 Hereditary Hemorrhagic Telangiectasia
(Osler–Weber–Rendu Disease):GIT
 Pulmonary / cerebral complications including pulmonary
hypertension, paradoxic emboli, air emboli, cerebral abscesses
may come on silently secondary to pulmonary AVMs&need to be
managed proactively.
 In patients with pulmonary AVMs, routine antibiotic dental
prophylaxis is recommended for both dental & endoscopic
procedures.
 Prophylactic management of the pulmonary AVMs by
embolization or surgical resection should be considered when
AVMs are : 3 mm.
 Endothelin-receptor antagonists have been tried.
 Hereditary Hemorrhagic Telangiectasia
(Osler–Weber–Rendu Disease):GIT
 Patients with hepatic AVMs can present with HF, edema,
increased liver function tests, ascites, variceal bleeding, or
encephalopathy,managed intensively with medical means.
 Embolization is used only for palliation given the incidence of
hepatic necrosis.
 Invasive procedures as liver biopsy or ERCP should be avoided
given the respective risks for bleeding / sepsis.
 When medical management fails, referral for a liver transplant
used with increasing success.
 Improvement in nose bleeds/telangiectases with the vascular
endothelial growth factor antagonist, bevacizumab, with
interferon, suggesti trial in HHT AVMs.
 Melanoma: case

 A 92-year-old man presented with a 2-week history of dull,

constant periumbilical pain associated with nausea, bilious emesis,
, decreased appetite.
 Physical examination revealed a soft abdomen with epigastric
tenderness.
 Abdominal radiographs revealed changes consistent with a small-
bowel obstruction.
 CT scan showed a small bowel mass with intussusception

 Five years previously, the patient had had a malignant mole

removed from his right forearm
Melanoma: case
 Melanoma:

 Melanoma is a malignant tumor arising from melanocytes related

to both genetic predisposition& sun exposure.
 Melanoma:skin

 Superficial spreading melanoma is the most common type.

 It generally presents as an asymmetric macule with irregular
borders, color variation& an enlarging diameter to > 6 mm.
 It usually is found on the trunk in men&on the legs in women
from 30 to 50 years of age.
 Nodular melanoma is less common & generally a blue- or
blackcolored nodule that may ulcerate & develops rapidly over
several months, generally on the trunk, head, or neck
 Melanoma:GIT

 Skin for suspicious lesions should be an integral part of PE.

 Melanoma is the 5th most common cancer in men& the 6th most
common cancer in women.
 Referral to a dermatologist is advised for any patient noted to have
atypical, or a large number of, nevi.
 RFs: fair skin with freckles, H/O intermittent sun burns&
dysplastic nevi or melanoma.
 Melanoma is the most common metastatic tumor to the GI, so any
patient with H/O melanoma, even in the distant past& symptoms of
anemia, IO&/or intussusception, bleeding, or abd pain should be
evaluated for metastases.
 Barium/CT may not detect all tumor deposits reliably.
 Melanoma:management

 Surgical excision curative for stages I& II with no nodal or

metastatic disease.
 Stage III: evidence of either microscopic or macroscopic nodal
disease , treated with wide excision/ nodal dissection; interferon-
alfa 2b as adjuvant therapy.
 Stage IV with metastases are treated with chemotherapy,
radiation,immunotherapy, but the prognosis is very poor, with
only 5% surviving 5 years.
 Melanoma in the GI tract may be primary or secondary.

 A primary melanoma can arise from any bowel site.

 More commonly,melanoma is metastatic from a prior skin lesion.

 Melanoma:management

 Importantly, metastases may present at the time of the primary

diagnosis or decades later.
 Metastatic deposits to the gut may be identified by using
fluorodeoxy-glucose PET, which appears to offer greater
diagnostic accuracy than CT/Ba.
 Although the prognosis is very poor for metastases to the liver / GI
tract, surgical resection has resulted in both efficacy in palliating
symptoms as obstruction /bleeding & improved survival in select
cases.
 Hepatitis C:

 Chronic HCV is associated with extrahepatic manifestations,

including dermatologic conditions as mixed cryoglobulinemia,
porphyria cutanea tarda& lichen planus.
 The efficacy of IFN on skin features are highly variable.

 dermatologic side effects of IFN therapy are common, with or

without HCV infection& may complicate assessment of HCV-
associated dermatologic disorders.
 Pruritic,eczematous lesions are most common& often resolve on
completion of therapy without dosage alteration.
 IBD: Dermatological features

 Skin - erythema nodosum 2-4%.

 Pyoderma gangrenosum 1-2%

 Mouth - aphthous ulcers 10%.

 A wide variety of cutaneous conditions are associated with IBD.

 In general, their course parallels the GI status,but can precede or

follow the diagnosis of the IBD.
 Dermatologists can help clinicians to reach the correct diagnosis &
the best treatment approach, but treatment of the underlying IBD
is essential for the control of the cutaneous associated conditions.
 IBD: Dermatological features

 Seen in 20%, slightly higher in CD than in UC& include:

 Pyoderma gangrenosum(PG).

 Bowel-associated dermatosis-arthritis syndrome.

 Cutaneous Crohn’s disease.

 Erythema nodosum

 Avariety of vasculitis.
 IBD dermatological features: PG

 The most severe dermatologic manifestation.

 Are ulcerating necrotic plaques on their lower extremities.

 60% with PG have an associated disease, with Crohn’s being the

most frequent but other diseases including RA,AML, MM& HIV.
 Certain drugs, like G-CSF& interferon

 2-10% with IBD will eventually develop PG.

 Often parallels the severity of their disease,but may precede or

follow episodes of IBD& may initially have a flare associated with
IBD, eventually become chronic& protracted.
 IBD dermatological features: PG

 Often have atypical presentations with pustular &necrotic flares.

 PG tends to start with a single or multiple small pustular lesions
that eventually evolve into large ulcerated lesions.
 Another feature is pathergy: i.e., new lesions triggered by trauma.

 A pustular lesion triggered by trauma may not evolve into an

ulcer &may be the only cutaneous sign of IBD.
 The peristomal variant,develop adjacent to the colostomy.
 IBD dermatological features: PG

 DD:
 Infections: deep fungal infs, bacterial pyodermus, TB.

 Vasculitis, Wegener’s granulomatosis, hallogenodermas,

secondary to high ingestion of iodine or bromides present with
suppurative ulcerated lesions resembling PG.
 IBD dermatological features: PG

 Treatment of the associated disease is the critical point.

 In IBD, infliximab is the treatment of choice

 For patients with other associated conditions, the standard of care

is systemic steroids, either oral prednisone or methyl-
prednisolone, with cyclosporine or mycofenolate.
 Other treatments include thalidomide andmycophenolate mofetil.

 Other treatment: plasmapheresis, IV Ig,absorption apheresis.

 Surgery as debridement and allografts avoided utill the lesions

are quiescent because of pathergy.
 Localized: treated topically with potent steroids or tacrolimus or
intralesional triamcinolone.
 IBD dermatological features: Bowel-Associated
Dermatosis-Arthritis Syndrome (bowel bypass syndrome)
 Also be associated with IBD secondary to an overgrowth of
bacteria: Streptococci, Dientamoeba fragilis, or E coli.
 Present with flu-like symptoms.

 Bacteria proteoglycan activate complement causing pap/pustules,

severe tenosynovitis &pathergy of cutaneous lesions.
 Microscopy shows multiple neutrophils & a low level of vasculitis.

 Treatment is for the underlying IBD, with resection, if indicated.

 Systemic steroids must be avoided, as may worsen the problem.

 Probiotics as used for pouchitis& antibiotics: minocycline,

erythromycin, or metronidazole, may be useful.
 IBD dermatological features: Cutaneous CD.
 A granulomatous, noncaseating skin lesion separated from the GI
tract by normal skin.
 It is very rare: 20% have a negative GI history& only
subsequently develop IBD.
 The lesions may be adjacent to the GI tract at both ends; perioral
or perianal, or more distant& noncontiguous metastatic lesions.
 PPD &CXR done to differentiate from TB& sarcoidosis.

 Trt: Metronidazole of choice& If only a few lesions, topical or

intralesional steroids may be useful.
 Ssulfasalazine/azathioprine being effective.

 Surgical excision is often complicated by wound dehiscence.

 IBD dermatological features: EN
 The most common complication of IBD, other than aphthous
dermatitis.
 Presents with multiple,painful, deep nodules on extremities

 The nodules,unlike PG do not become fluctuant or ulcerated.

 In some,may be large& highly inflamed, while in others minimal

skin changes with only deep pain.
 Occurs in 3–10% UC& 4–15% CD

 The nodules tend to appear during the acute phase of IBD.

 Unlike PG—a chronic, ongoing process—it is short-lived process.

 DD: Srept inf, TB, Sarcoid.

 IBD dermatological features: EN
 The treatment should be aimed at the triggering event.
 NSAIDs like indomethacin, are often prescribed for 2 or 3 wk,
along with bed rest, leg elevation, prednisone taper, intralesional
or intramuscular triamcinolone in patients with severe flares.
 Second-line therapy, rarely needed as colchicine,
hydroxchloroquine, or dapsone.
 Celiac dis dermatological features:
 Dermatitis herpetiformis is well known accompanying CD
 DH: Itchy, blistering skin, rash usually on elbows, knees, buttocks,
back, diagnosed with skin biopsy
 Cutaneous,mucosal, nail, hair findings were detected in 74.5%,
27.3%, 20.0%,7.3% of patients, respectively.
 The most prevalent dermatologic diagnosis was xerosis (69.1%).

 No significant relationship was detected between the cutaneous

findings& the duration of illness.
 However, the duration was longer in patients with mucosal
findings compared to those without mucosal findings.
 It was found that all patients without cutaneous findings were on
a strict gluten-free diet.
 Celiac dis dermatological features:
 Pathophysiology: an abnormal small intestinal permeability allow
the crossing of endogenous or exogenous antigens may provoke the
immunological response, common immune mechanisms, vascular
alterations & vitamin/aminoacid deficiency secondary to
malabsorption.