Gastrointestinal Manifestations of Dermatologic Disorders

Prepared by:Dr.Mohammad Shaikhani.

Assistant professorSulaimani UniversityCollege of Medicine

Dept of Medicine.

hshields@bidmc.harvard.edu

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

Epidermolysis Bullosa: 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

Epidermolysis Bullosa:

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 features:

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.

Management:

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.

Mastocytosis: Case

Mastocytosis: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.

Mastocytosis: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.

Mastocytosis: 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 GIT organs in 11%–25%, with the stomach &small bowel being the source of bleeding more than the colon.

Manifestations of bleeding, as IDA, generally begin in 5th decade. Other clinical manifestations occur secondary to hepatic AVMs,

including high-output CHF, portal HT& 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) is the predominant shunting (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 local treatments as endonasal laser coagulation or argon plasma coagulation & septodermoplasty.

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 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 HT, paradoxic emboli, air emboli, cerebral abscesses may ocur 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 of 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.

Mucocutaneous hyperpigmentation presents as dark blue to dark brown mucocutaneous macules around the mouth, eyes, and nostrils, in the perianal area, on the buccal mucosa, and on the fingers

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.