Ikhtisar

Many disorders of the alimentary tract have dermatologic manifestations (see the Table below).
Banyak gangguan pada saluran pencernaan telah manifestasi dermatologi (lihat Tabel di bawah).
A thorough understanding of the cutaneous/gastrointestinal (GI) relationship can alert the astute
clinician to occult disease within the GI tract. Sebuah pemahaman menyeluruh tentang hubungan
/ kulit gastrointestinal (GI) dapat waspada dokter cerdas untuk okultisme penyakit dalam saluran
pencernaan. This review attempts to explore this relationship by describing disorders involving
both the GI tract and the skin. Kajian ini mencoba untuk mengeksplorasi hubungan ini dengan
menjelaskan gangguan melibatkan kedua saluran GI dan kulit.

Dermatologic Manifestations of Alimentary Disorders Dermatologic Manifestasi Gangguan

pencernaan

(Open Table in a new window) (Open Tabel di jendela baru)

Dermatologic Manifestation Dermatologic GI Abnormality GI Disorder Kekacauan

Manifestasi Abnormalitas
Periorificial granulomas Periorificial Malabsorption Crohn disease Penyakit
granuloma Malabsorpsi Crohn
Koilonychia Koilonychia Esophageal webs Plummer-Vinson
Esophagus web syndrome Plummer-
Vinson sindrom
Liver disease Hemochromatosis
Penyakit hati Hemochromatosis
Palmoplantar keratoderma Palmoplantar Esophageal Howel-Evans syndrome
keratoderma Esophagus BAB-Evans sindrom
Acral rash Acral ruam Bazex syndrome [1]
carcinoma bisul sindrom Bazex [1]
kanker

Telangiectasia Telangiectasia Esophagitis Scleroderma Scleroderma

Esophagitis
GI bleeding Hereditary hemorrhagic
Perdarahan GI telangiectasia Hemoragik
herediter telangiectasia
Cirrhosis Sirosis Liver disease secondary to
alcohol or other factors
Hati sekunder untuk faktor
alkohol atau penyakit lain
Vesicles/blisters/erosions Vesikel / lecet / erosi Esophageal webs Epidermolysis bullosa
Esophagus web Epidermolysis bullosa
Esophageal erosion Pemphigus vulgaris
Esophagus erosi Pemphigus vulgaris
Pyloric atresia Pyloric Junctional epidermolysis
 atresia bullosa Junctional
epidermolysis bullosa
Hepatitis Hepatitis Porphyria cutanea tarda
Porfiria cutanea tarda
Malabsorption Dermatitis herpetiformis
Malabsorpsi and celiac sprue
Dermatitis herpetiformis
dan sariawan celiac
Velvety hyperpigmented plaques, tripe palms, Gastric cancer Kanker Malignant acanthosis
mucosal hyperplasia Beludru hiperpigmentasi lambung nigricans Ganas acanthosis
plakat, telapak tangan babat, hiperplasia nigricans
mukosa
Yellowish papules, "chicken skin" Kekuningan GI bleeding Pseudoxanthoma
papula, "kulit ayam" Perdarahan GI elasticum
Pseudoxanthoma
elasticum
Eruptive xanthomas Letusan xanthomas Pancreatitis Primary biliary cirrhosis
Pankreatitis Sirosis bilier primer
Biliary cirrhosis Sister Mary Joseph nodule
Sirosis bilier Suster Maria Yusuf bintil
Panniculitis Pancreatic Pankreas Pancreatitis Pancreatitis Pankreatitis
Panniculitis Pankreatitis
Pancreatic Pankreas
Pancreatic Pankreas
cancer kanker
cancer kanker

Erythema nodosum Malabsorption Inflammatory bowel

Eritema nodosum Malabsorpsi disease Radang usus
Skin tumors Tumor Multiple cysts GI polyps Colon Gardner syndrome
kulit Beberapa kista cancer GI kanker Sindrom Gardner
Sebaceous Sebaceous polip Colon Muir-Torre syndrome
Muir-Torre sindrom
neoplasms, multiple
neoplasma, beberapa

keratoacanthomas
keratoacanthomas

Trichilemommas Cowden syndrome

Trichilemommas Cowden sindrom
Hyperpigmentation Mucosal macular GI polyps Upper GI Peutz-Jeghers syndrome
Hiperpigmentasi Mukosa makula cancer Polip Upper GI Peutz-Jeghers sindrom
GI kanker
Diffuse macular GI polyps GI cancer Cronkhite-Canada
 Diffuse makula GI GI kanker polip Cronkhite-Kanada
Diffuse Membaur Hepatomegaly Hemochromatosis
Cirrhosis Hemochromatosis
Hepatocellular
carcinoma
Hepatomegali Sirosis
Hepatocellular
karsinoma
Plaques, acral Plak, acral Hepatitis Hepatitis Necrolytic acral erythema
Necrolytic acral eritema
Lichenoid papules/plaques Lichenoid papula / Hepatitis Hepatitis Lichen planus Lichen
plakat planus
Hepatomegaly [2] Sarcoidosis Sarkoidosis
Hepatic lesions
Hepatomegali [2] hati
lesi
Papules that heal with atrophic scars Papula Perforation Perforasi Malignant atrophic
yang menyembuhkan dengan bekas luka atrofi papulosis [3] atrofi
papulosis ganas [3]
Vascular malformation Kelainan Vaskular GI bleeding Blue rubber bleb nevus
Perdarahan GI syndrome Blue karet lepuh
sindrom nevus
Ulcers with undermined borders Borok dengan Malabsorption Pyoderma gangrenosum
perbatasan dirusak Malabsorpsi and inflammatory bowel
disease [4] Pioderma
gangrenosum dan penyakit
radang usus [4]
Palpable purpura Teraba purpura Abdominal pain Sakit Henoch-Schönlein purpura
perut Purpura Henoch-
Schönlein
Plaques, intertriginous Plak, intertriginosa Malabsorption Acrodermatitis
Malabsorpsi enteropathica
Acrodermatitis
enteropathica

Dermatology and the Pharynx Dermatologi dan faring

Kaposi sarcoma Kaposi sarcoma

Kaposi sarcoma (KS) is a neoplasm of vascular endothelial and lymphoreticular cells that can
involve the skin and numerous visceral organs. Sarkoma Kaposi (KS) adalah neoplasma sel
endotel dan lymphoreticular vaskular yang dapat melibatkan kulit dan organ visceral banyak.
The disease can manifest in 4 distinct forms: classic, endemic, iatrogenic, and epidemic.
Penyakit yang dapat terwujud dalam 4 bentuk yang berbeda: klasik, endemik, iatrogenik, dan
epidemi. Originally described by Kaposi in 1872, the prevalence of the disease has risen
dramatically in the United States over the past 20 years with the spread of AIDS (the epidemic
form of KS). Awalnya dijelaskan oleh Kaposi pada tahun 1872, prevalensi penyakit ini telah
meningkat secara dramatis di Amerika Serikat selama 20 tahun terakhir dengan penyebaran
AIDS (bentuk epidemi KS).

Human herpesvirus type 8 (HHV-8) has been implicated in the pathogenesis of KS in both HIV-
infected and non-HIV–infected patients. [5, 6, 7] KS may in fact be a hyperplasia caused by
infection with HHV-8, rather than a sarcoma. Herpesvirus Manusia tipe 8 (HHV-8) telah terlibat
dalam patogenesis KS di kedua-terinfeksi dan non-terinfeksi HIV pasien HIV. [5, 6, 7] KS mungkin
sebenarnya menjadi hiperplasia disebabkan oleh infeksi HHV- 8, bukan suatu sarkoma.
Supporting evidence includes lack of clonality, multifocality, symmetry, absence of metastasis,
and spontaneous regression with immune reconstitution. Bukti pendukung adalah kurangnya
clonality, multifocality, simetri, tidak adanya metastasis, dan regresi spontan dengan pemulihan
kekebalan.

The cutaneous lesions of KS (occurring primarily in the classic and epidemic forms) begin as
pink or red macules, which darken and become increasingly papular as they enlarge. Lesi kulit
KS (terjadi terutama dalam bentuk klasik dan epidemi) mulai makula sebagai pink atau merah,
yang gelap dan menjadi semakin papular saat mereka memperbesar. Although the classic KS
lesions tend to occur on the legs and feet, the epidemic KS lesions are more common on the face
and trunk. Meskipun lesi KS klasik cenderung terjadi pada kaki dan kaki, KS epidemi lesi lebih
sering terjadi pada wajah dan batang.

Treatment of localized cutaneous disease includes radiotherapy, surgical excision, systemic

therapy, or intralesional chemotherapy. Pengobatan penyakit kulit lokal meliputi radioterapi,
eksisi bedah, terapi sistemik, atau kemoterapi intralesi. In patients with widespread disease,
careful consideration must be given to potential adverse effects. [8] Amongst the agents that attain
a 30% response rate are interferons, antiviral agents (eg, zidovudine), cytotoxic agents (eg,
vinblastine, etoposide), and combination therapy. Pada pasien dengan penyakit luas,
pertimbangan cermat harus diberikan untuk dampak negatif. [8] Di antara para agen yang
mencapai tingkat respons 30% adalah Interferon, obat antivirus (misalnya, AZT), agen sitotoksik
(misalnya, vinblastine, etoposid), dan kombinasi terapi. For HIV-related KS with a low CD4
count or high viral load, antiretroviral therapy is the first-line therapy. [9] In aggressive disease,
liposomal doxorubicin or daunorubicin are the first-line chemotherapeutics. Untuk terkait KS
HIV dengan jumlah CD4 rendah atau viral load tinggi, terapi antiretroviral adalah terapi lini
pertama. [9] Pada penyakit agresif, doxorubicin liposomal atau daunorubisin adalah kemoterapi
lini pertama.

GI involvement occurs in 50-80% of patients with cutaneous KS and in almost 100% of those
with oral lesions (see the image below). keterlibatan GI terjadi pada 50-80% pasien dengan KS
kulit dan di hampir 100% dari mereka dengan lesi oral (lihat gambar di bawah). The GI tract may
be involved at any level, although the most frequently afflicted sites (in order) are the small
intestine, stomach, and esophagus. Saluran pencernaan mungkin terlibat di tingkat manapun,
meskipun situs yang paling sering menderita (dalam urutan) adalah usus perut, kecil, dan
kerongkongan. Oral lesions are most likely to affect the hard palate, followed in order of
frequency by the gingiva and the tongue. lesi oral yang paling mungkin mempengaruhi langit-
langit keras, diikuti urutan frekuensi oleh gusi dan lidah. In patients with non-HIV–associated
KS, both the skin and GI lesions tend to have a relatively indolent course. Pada pasien dengan
KS non-HIV-terkait, baik kulit dan lesi GI cenderung memiliki jalur yang relatif lamban. In
contrast, HIV-associated Kaposi lesions of the GI tract can have an aggressive clinical course,
leading to extensive hemorrhage or partial small bowel obstruction. Sebaliknya, terkait HIV
Kaposi lesi saluran pencernaan dapat memiliki kursus klinis agresif, menyebabkan perdarahan
yang luas atau obstruksi usus sebagian kecil. Treatment of symptomatic GI lesions involves laser
ablation or surgical excision. Pengobatan lesi GI melibatkan gejala ablasi laser atau bedah eksisi.

Oral Kaposi sarcoma in a patient with AIDS. Oral Kaposi

sarkoma pada pasien dengan AIDS. Note the characteristic purple hemorrhagic papules
coalescing into an irregular plaque. Perhatikan ungu papula hemoragik karakteristik
penggabungan ke dalam plak tidak teratur.

Dermatology and the Esophagus Dermatologi dan

Kerongkongan
Plummer-Vinson syndrome (Patterson-Brown-Kelly syndrome) Plummer-
Vinson syndrome (Patterson-Brown-Kelly sindrom)

Signs of Plummer-Vinson syndrome includes the mucocutaneous findings of koilonychia (brittle,

spoon-shaped nails; see the image below) early loss of teeth, development of cheilosis, atrophy
of the tongue, and angular stomatitis, along with iron deficiency anemia and the clinical
complaint of dysphagia. [10, 11] The disease is rare in patients younger than 30 years, and women
are affected in 80-90% of cases. Tanda-tanda sindrom Plummer-Vinson termasuk temuan
mukokutan dari koilonychia (rapuh, kuku berbentuk sendok, lihat gambar di bawah) hilangnya
awal gigi, pengembangan cheilosis, atrofi lidah, dan stomatitis sudut, bersama dengan anemia
kekurangan zat besi dan keluhan klinis disfagia. [10, 11] Penyakit ini jarang terjadi pada pasien
yang lebih muda dari 30 tahun, dan wanita yang terpengaruh dalam 80-90% kasus. Although the
earlier diagnosis of iron deficiency and the ready availability of iron replacement have made this
disease less common, the diagnosis of Plummer-Vinson syndrome nonetheless should be
considered in patients presenting with long-standing intermittent dysphagia. Meskipun diagnosis
awal kekurangan zat besi dan ketersediaan siap penggantian besi telah membuat penyakit ini
kurang umum, diagnosis sindrom Plummer-Vinson tetap harus dipertimbangkan pada pasien
dengan disfagia intermiten lama. Splenomegaly and edentia may aid in the diagnosis.
Splenomegali dan Edentia dapat membantu dalam diagnosis.
 Koilonychia. Koilonychia. Note the double concavity
(longitudinal and transverse) of the nails. Catatan cekung ganda (longitudinal dan transversal)
dari kuku.

Complications include progressive painless dysphagia, which is described by patients as a

choking sensation that worsens with solid foods. Komplikasi meliputi disfagia menyakitkan
progresif, yang digambarkan oleh pasien sebagai sensasi tersedak yang memburuk dengan
makanan padat. Severe iron deficiency anemia can lead to devastating neurodegenerative
consequences in children via hypomyelination. Parah anemia defisiensi zat besi dapat
mengakibatkan konsekuensi yang menghancurkan neurodegenerative pada anak-anak melalui
hypomyelination. Iron is critical for oligodendrocyte and dopaminergic metabolism. Besi sangat
penting untuk metabolisme oligodendrocyte dan dopaminergik. In 5-10% of patients with a
postcricoid web, esophageal carcinoma eventually may develop (see the image below). Pada 5-
10% pasien dengan web postcricoid, karsinoma esofagus pada akhirnya bisa terjadi (lihat gambar
di bawah).

Postcricoid web in a patient with Plummer-Vinson syndrome.

Postcricoid web pada pasien dengan sindrom Vinson Plummer. Note the 2 small openings within
the web at the 2- and 6-o'clock positions, representing a significantly compromised proximal
esophageal lumen. Perhatikan 2 lubang kecil di dalam web pada 2 - dan 6-pukul posisi, mewakili
dikompromikan lumen esofagus proksimal secara signifikan. Reprinted with permission from
Gastrointestinal Endoscopy, Second edition, Gower Medical Publishing, New York, 1991.
Dicetak ulang dengan izin dari gastrointestinal Endoscopy, Edisi Kedua, Gower Medical
Publishing, New York, 1991.

Diagnosis involves laboratory evaluation to confirm the presence of iron deficiency anemia and
cineradiography to detect esophageal webs, which occur in the first 2-4 cm of the esophagus.
Diagnosis melibatkan evaluasi laboratorium untuk mengkonfirmasi adanya anemia defisiensi
besi dan cineradiography untuk mendeteksi web kerongkongan, yang terjadi dalam 2-4 cm
pertama dari kerongkongan. Treatment involves iron supplementation, which often leads to rapid
resolution of the dysphagia. Pengobatan melibatkan suplementasi besi, yang sering menyebabkan
resolusi cepat disfagia tersebut. In patients who continue to complain of dysphagia, therapy
involves rupture of the esophageal web either by endoscopy or bougienage. Pada pasien yang
terus mengeluh disfagia, terapi melibatkan pecahnya esofagus web baik dengan endoskopi atau
bougienage.

Epidermolysis bullosa Epidermolysis bullosa

The name epidermolysis bullosa (EB) is given to a diverse group of rare inherited diseases that
cause fragile skin. [12] The skin of these patients tends to form blisters at sites of minimal trauma,
with symptomatology beginning at birth or early infancy. Para epidermolysis Nama bullosa (EB)
diberikan kepada berbagai kelompok penyakit warisan langka yang menyebabkan kulit rapuh. [12]
Kulit pasien ini cenderung untuk membentuk lepuh di situs dari trauma minimal, dengan awal
simtomatologi pada saat lahir atau masa kanak-kanak awal. Clinical phenotypes include marked
skin fragility, blisters, and erosions over trauma-prone parts of the body. fenotipe klinis termasuk
ditandai kerapuhan kulit, lecet, dan erosi lebih dari bagian rawan trauma tubuh. Chronic trauma
and healing leads to significant scarring and milia formation. trauma kronis dan menyebabkan
penyembuhan yang signifikan dan pembentukan jaringan parut milia. The disease is divided
clinically into the following 3 forms depending on the layer of blister formation: dystrophic
(beneath lamina densa), junctional (within the lamina lucida), and simplex (intraepidermal).
Penyakit ini secara klinis dibagi ke dalam 3 bentuk berikut, tergantung pada lapisan
pembentukan blister: dystrophic (di bawah lamina densa), junctional (dalam lamina lucida), dan
simplex (intraepidermal).

In dystrophic EB, oral erosions and early tooth decay are frequent manifestations. Dalam EB
dystrophic, erosi lisan dan kerusakan gigi awal adalah manifestasi sering. In addition, these
patients have esophageal strictures, which tend to be located in the upper third of the esophagus,
but they also can be seen in the lower third of the esophagus. Selain itu, pasien striktur esofagus,
yang cenderung terletak di ketiga atas kerongkongan, tetapi mereka juga dapat dilihat pada
sepertiga bagian bawah kerongkongan. The cause of these strictures is likely caused by repetitive
trauma of food ingestion. Penyebab penyempitan ini kemungkinan disebabkan oleh trauma
berulang menelan makanan. Lesions generally become symptomatic before age 30 years. Lesi
umumnya menjadi gejala sebelum usia 30 tahun. Therapy focuses on strict adherence to a soft
diet, with mechanical dilation, [13] surgical excision, and feeding gastrostomy as alternative
choices. Terapi berfokus pada kepatuhan ketat untuk diet lunak, dengan pelebaran mekanis, [13]
eksisi bedah, dan makan gastrostomy sebagai pilihan alternatif.

Other complications of dystrophic EB include the development of esophageal webs,

constipation, and anal stenosis. [14] An analysis of 20 consecutive patients with recessive
dystrophic EB evaluated at a regional center demonstrated that all 20 had upper GI complaints,
with most patients exhibiting abnormalities on endoscopic evaluation. Komplikasi lain dari EB
dystrophic mencakup pengembangan jaring kerongkongan, sembelit, dan stenosis anal. [14]
Analisis 20 pasien berturut-turut dengan EB dystrophic resesif dievaluasi di pusat regional
menunjukkan bahwa semua 20 telah GI keluhan atas, dengan sebagian besar pasien
menunjukkan kelainan evaluasi endoskopik. Patients with junctional EB have many of the
complications of dystrophic EB and may develop pyloric atresia. [15] In patients with severe EB
of any type, nutritional deficiency, anemia, and growth retardation may develop over time,
principally from the presence of oral and GI complications. Pasien dengan EB junctional
memiliki banyak komplikasi EB dystrophic dan dapat mengembangkan atresia pilorus. [15] Pada
pasien dengan EB berat dari jenis apa pun, kekurangan gizi, anemia, dan kelambatan
pertumbuhan dapat berkembang dari waktu ke waktu, terutama dari hadirat oral dan GI
komplikasi.

Scleroderma (systemic sclerosis) Scleroderma (sklerosis sistemik)

Scleroderma describes a multisystem disease of unknown etiology that causes fibrotic change in
the skin, blood vessels, lungs, heart, kidneys, and GI tract. [16, 17] The disease affects all races and
occurs worldwide, with clinical manifestations appearing most often in the third to fifth decade
of life. Scleroderma menjelaskan penyakit multisistem etiologi tidak diketahui yang
menyebabkan perubahan fibrosis pada kulit, pembuluh darah, paru-paru, jantung, ginjal, dan
saluran pencernaan. [16, 17] Penyakit ini mempengaruhi semua ras dan terjadi di seluruh dunia,
dengan manifestasi klinis yang paling sering muncul dalam ketiga untuk dekade kelima
kehidupan. In population studies, the prevalence of scleroderma has varied from 19-75 cases per
100,000 population. Dalam studi populasi, prevalensi scleroderma bervariasi 19-75 kasus per
100.000 penduduk. The systemic form of the disease is divided broadly into diffuse cutaneous
scleroderma and limited cutaneous scleroderma. Bentuk sistemik penyakit ini dibagi luas dalam
scleroderma kulit difus dan skleroderma kulit terbatas.

The dermatologic changes in scleroderma are progressive over time, generally beginning with
the appearance of pitting edema on the face, hands, or feet (see the image below). perubahan
dermatologi yang di skleroderma bersifat progresif dari waktu ke waktu, umumnya dimulai
dengan munculnya pitting edema pada wajah, tangan, atau kaki (lihat gambar di bawah). Skin
sclerosis begins, initially on the fingertips, and then spreads to the hands, with a relative sparing
of the feet. Kulit sclerosis dimulai, awalnya pada ujung jari, dan kemudian menyebar ke tangan,
dengan hemat relatif kaki. A careful examination may reveal curved nails (a result of the
underlying skin shrinking away while the nail does not) or periungual telangiectasia.
Pemeriksaan yang seksama dapat mengungkapkan kuku melengkung (akibat dari kulit yang
mendasari menyusut pergi sementara kuku tidak) atau telangiectasia periungual. On the face,
hyperpigmentation and hypopigmentation can occur, along with a tightening of the skin over the
nose, mouth, and forehead. Pada hiperpigmentasi, wajah dan hipopigmentasi dapat terjadi,
bersama dengan mengencangkan kulit di atas mulut, hidung, dan dahi. The disease exhibits a
variable course. Pameran penyakit saja variabel. Patients who demonstrate a rapid progression to
total body involvement (2-3 y) are also more likely to develop changes in the visceral organs,
such as the heart, lungs, and kidneys. Pasien yang menunjukkan kemajuan cepat untuk
keterlibatan tubuh total (2-3 y) juga lebih mungkin untuk mengembangkan perubahan pada
organ-organ visceral, seperti paru-paru jantung,, dan ginjal.
 Scleroderma affecting the hands. Scleroderma mempengaruhi
tangan. Note the taut appearance of the skin and the curved nails. Perhatikan penampilan
kencang pada kulit dan kuku melengkung.

Diffuse cutaneous disease manifests early with fatigue, arthralgias, carpal tunnel syndrome,
puffy fingers, swollen feet and legs, or a positive serum antinuclear antibody test before
developing either Raynaud phenomenon or definite skin thickening. Diffuse memanifestasikan
penyakit kulit dini dengan kelelahan, arthralgias, carpal tunnel syndrome, jari bengkak, kaki
bengkak dan kaki, atau antinuclear tes serum positif antibodi sebelum berkembang baik
fenomena Raynaud atau penebalan kulit pasti. Few patients develop systemic manifestations of
disease without ever presenting with Raynaud phenomenon. Beberapa pasien mengembangkan
manifestasi sistemik dari penyakit tanpa pernah menyajikan dengan fenomena Raynaud.
Findings distinct to diffuse cutaneous disease include capillary dropout, the presence of palpable
tendon friction rubs, and the appearance of finger joint contractures. Temuan yang berbeda untuk
meredakan penyakit kulit termasuk putus kapiler, kehadiran menggosok gesekan tendon teraba,
dan penampilan jari kontraktur sendi. The pace of skin thickening is rapid in diffuse cutaneous
systemic sclerosis, with extension proximally to forearms, arms, and legs within several months.
Kecepatan penebalan kulit cepat dalam sclerosis sistemik menyebar kulit, dengan ekstensi
proksimal ke lengan bawah, lengan, dan kaki dalam waktu beberapa bulan. Internal organ
dysfunction is frequent in the early diffuse cutaneous form, with severe visceral dysfunction
most often occurring during the first 3 years of disease. disfungsi organ internal adalah sering
dalam bentuk difus awal kulit, dengan disfungsi visceral parah paling sering terjadi selama 3
tahun pertama penyakit.

Patients with the limited cutaneous form most frequently have Raynaud phenomenon with
eventual progression in years to CREST (calcinosis, Raynaud phenomenon, esophageal
dysmotility, sclerodactyly, and telangiectasia) syndrome (see the image below). Pasien dengan
bentuk kulit yang paling sering terbatas memiliki fenomena Raynaud dengan perkembangan
akhirnya di tahun-tahun CREST (calcinosis, fenomena Raynaud, dysmotility kerongkongan,
sclerodactyly, dan telangiectasia) sindrom (lihat gambar di bawah). Mat telangiectasias, which
appear on peripheral sites (eg, hands, feet, mouth), are macular lesions ranging from 2-10 mm
and are polygonal or oval. Mat telangiectasias, yang muncul di situs perifer (misalnya, tangan,
kaki, mulut), adalah lesi makula berkisar 2-10 mm dan poligonal atau oval. The presence of
serum anticentromere antibody is a strong clue to the classification into the localized cutaneous
form. Kehadiran antibodi serum anticentromere adalah petunjuk yang kuat untuk klasifikasi ke
dalam bentuk kulit lokal.
 Telangiectases in the gastric mucosa of a patient with Osler-
Weber-Rendu syndrome. Telangiectases di mukosa lambung seorang pasien dengan-Weber-
Rendu sindrom Osler. The lesions can be seen most prominently at the 2-o'clock position
proximally and the 3-o'clock position distally. Lesi dapat dilihat paling menonjol pada-posisi jam
2 proksimal dan-posisi jam 3 distal. Note the prominent red color of the lesions. Perhatikan
warna merah menonjol dari lesi. Although these particular lesions appear flat, some GI
telangiectasias may be slightly elevated. Meskipun lesi tertentu muncul datar, beberapa
telangiectasias GI mungkin akan sedikit meningkat. Reprinted with permission from
Gastrointestinal Endoscopy, Second edition, Gower Medical Publishing, New York, 1991.
Dicetak ulang dengan izin dari gastrointestinal Endoscopy, Edisi Kedua, Gower Medical
Publishing, New York, 1991.

As many as 90% of patients with scleroderma demonstrate GI manifestations. [18] Indeed, these
symptoms may be the first manifestation of scleroderma and may precede the diagnosis by
months or years. Sebanyak 90% dari pasien dengan scleroderma menunjukkan manifestasi GI.
[18]
Memang, gejala-gejala ini mungkin merupakan manifestasi pertama scleroderma dan dapat
mendahului diagnosa dengan bulan atau tahun. As in other organ systems, GI disease in
scleroderma results from the excess collagen production, enhanced immunologic activity, and
flawed cellular immune response. Seperti pada sistem organ lain, GI penyakit dalam hasil
scleroderma dari kelebihan produksi kolagen, aktivitas imunologi yang disempurnakan, dan
respon imun seluler cacat. The most commonly affected areas are the lower two thirds of the
esophagus, the mid duodenum, jejunum, and large intestine. Daerah yang paling sering terkena
adalah dua pertiga lebih rendah dari kerongkongan, pertengahan duodenum, jejunum, dan usus
besar. The esophageal symptoms of scleroderma include a feeling of premature fullness, reflux
esophagitis, dysphagia, and epigastric pain, all of which stem from an incompetent lower
esophageal sphincter. Gejala-gejala terserang scleroderma termasuk perasaan kenyang prematur,
esophagitis refluks, disfagia, dan nyeri epigastrium, yang semuanya berasal dari sfingter
esofagus tidak kompeten lebih rendah. As with other forms of reflux esophagitis, Barrett
esophagus may develop, with the accompanying potential to transform to adenocarcinoma.
Seperti bentuk-bentuk lain dari esophagitis refluks, esofagus Barrett mungkin berkembang,
dengan potensi atas mengubah untuk adenokarsinoma.

Involvement of the stomach and small bowel in scleroderma is seen in approximately 50% of
cases. Symptoms include anorexia, early fullness, diarrhea, nausea/vomiting, and obstipation.
The causes of these ailments stem from impaired motility, which, in turn, leads to chronic
intestinal pseudo-obstruction, malnutrition, and bacterial overgrowth. Treatment of the
underlying causes involves the use of promotility agents on a regular basis, with antibiotic
therapy used intermittently to reduce bacterial growth. As in many chronic bacterial infections,
the development of resistant organisms is a concern with long-term use of antibiotics. When
prolonged antimicrobial therapy is necessary, multiple broad-spectrum antibiotics on a rotating
basis have been used with some success.

Colonic involvement has been demonstrated by barium studies to affect between 10-50% of
patients with scleroderma. Changes within the large intestine may result in chronic constipation,
fecal impaction, and bowel obstruction. Involvement of the anal sphincter may lead to
incontinence or even prolapse. Finally, overt or occult bleeding may develop as a result of
trauma to telangiectasias, which may appear anywhere throughout the bowel. Treatment is
symptomatic in all cases. Because the patient may require many years of therapy, careful
consideration for the adverse effects of various promotility or antimotility agents should be
undertaken.

Pemphigus vulgaris Pemphigus vulgaris

Pemphigus vulgaris (PV) is an autoimmune blistering disorder characterized by loss of cell-to-

cell adhesion in the epithelial suprabasal layer. Clinical manifestations include skin and mucous
membranes findings that can also affect the esophagus. [19, 20, 21] The incidence of PV is
approximately 1 case in 100,000 population, with a higher prevalence in people of Jewish or
Mediterranean descent; the prevalence of esophageal involvement has not yet been firmly
established, although a paper in The Lancet found evidence of esophageal involvement in 7 of 8
patients with PV who underwent endoscopy (87.5%).

Skin lesions range in size from 1-10 cm, and they are bullous, superficial, and easily ruptured by
trauma. Denuded areas are partially or totally covered with crust that heal poorly. Characteristic
findings on examination include lateral extension into adjacent tissue with palpation of normal-
appearing skin or the bullae spread phenomenon, which is when pressure on an intact bulla
forces fluid to spread under adjacent tissue.

Mucosal sites also commonly are involved, including the oral mucosa (often the presenting site),
anus, cervix, and conjunctivae. In 1970, Raque et al first described involvement of the
esophagus, and it has been noted in multiple subsequent case reports. Antigenic confirmation of
the disease correlation occurred in 1998, with the discovery that the target cell adhesion
molecule of the PV autoantibodies to desmoglein 3 is strongly expressed in the esophageal
epithelia.

Symptoms of esophageal involvement include persistent sore throat, dysphagia, and

odynophagia. In extreme cases, serious problems such as esophageal stenosis have been
described. On endoscopy, the lesions can appear as bullae or red irregular erosions (likely
ruptured bullae) with a red border covered by a white exudate. Sloughing of the entire
esophageal lining in the form of a cast (esophagitis dissecans superficialis) may occur. Treatment
for PV (oral and esophageal) involves the administration of steroids or other immunosuppressive
agents such as azathioprine and methotrexate.
Dermatology and the Stomach
Acanthosis nigricans Acanthosis nigricans

This relatively common skin finding appears as a brown-to-black, smooth, velvety plaque found
in areas of skin folds, most commonly the neck, axillae, and groin (see the image below). An
infrequent but important accompanying finding is the presence of acanthosis palmaris, or tripe
palms, which appear as pronounced skin markings on the palmar surfaces of the hands together
with diffuse velvety cobbled or honeycombed surface. It was first described in 1890 by Pollitzer
and Janovsky in a case suspected to be associated with an occult abdominal neoplasm.

Acanthosis nigricans (AN) in a patient with pancreatic cancer.

Note the papillomatous appearance of the axillary skin. This patient had previously been
diagnosed with typical AN related to diabetes mellitus. After a long period of stability, the AN
became much more severe and involved other parts of his skin, including the eyelids and scalp,
prompting the search for malignancy.

The mechanism responsible for the cutaneous lesions has not been identified. Tumor products
may have their effect on skin through activation of insulinlike growth factors or their receptors in
the skin. Alpha-transforming growth factors produced by tumor cells may have a role in
malignant acanthosis nigricans through epidermal growth factor receptors found in the skin. One
other hypothesis is that lytic factors produced by tumor cells may weaken the extracellular
matrix of the skin, predisposing to acanthosis nigricans. Independent of the malignant variant,
other identified associations include obesity, familial trait, diabetes mellitus, other endocrine
disorders, or drugs (eg, corticosteroids, estrogens, nicotinic acid). Although the lesions are
asymptomatic, relief from any associated irritation can be attempted with oral and topical
retinoids, keratolytics, topical steroids, and oral cyproheptadine.

In patients with acanthosis nigricans, the possibility of an intra-abdominal malignancy should be

considered, especially in patients without an obvious predisposing condition. [22] Clinical features
such as a large number of plaques, weight loss, rapid progression of lesions, or the discovery of
plaques in unusual locations, such as the lips, oral mucosa, hands, and genitalia, should be
additional alerting factors. Indeed, the skin lesions of malignant acanthosis nigricans often are
discovered prior to the cancer diagnosis. The presence of tripe palms heralds an underlying
cancer in 94% of patients. The malignancies associated with acanthosis nigricans include
adenocarcinoma (85% of cases), of which gastric carcinoma is present in 60%. Other reported
sites of malignancy include the lung, bladder, endometrium, adrenal, bile duct, kidneys, thyroid,
breast, liver, larynx, cervix, ovaries, prostate, and testicles. Nearly all cases are adenocarcinoma
despite the site of origin.
Prognosis is very poor for these patients, with a 1-year mortality rate of greater than 50%. In
patients with successful tumor resection, the skin lesions often disappear spontaneously over
time.

Sister Mary Joseph nodule Suster Maria Yusuf bintil

As head nurse and eventually skilled surgical assistant to William Mayo, MD, Sister Mary
Joseph was the first to note that the presence of a periumbilical nodule heralded an advanced
intra-abdominal malignancy (see the image below). [23, 24] The lesion was first coined "pants
button umbilicus" by Dr. Mayo in 1928, and the Sister's name was not attached to the lesion until
the 11th edition of Hamilton Bailey's Physical Signs in Clinical Surgery . Sebagai perawat
kepala dan akhirnya asisten bedah terampil untuk William Mayo, MD, Suster Maria Yusuf
adalah yang pertama untuk dicatat bahwa kehadiran nodul periumbilical digembar-gemborkan
suatu keganasan intra-abdominal lanjut (lihat gambar dibawah). [23, 24] Lesi pertama kali
diciptakan "tombol umbilikus celana" oleh Dr Mayo pada tahun 1928, dan Suster nama itu tidak
melekat pada lesi sampai edisi 11's Fisik Tanda Bailey Hamilton di Klinik Bedah. The cutaneous
finding is a firm, nontender nodule of red or purple hue that represents a metastasis from the
primary tumor. Temuan kutan adalah sebuah perusahaan, nontender nodul dari rona merah atau
ungu yang merupakan metastasis dari tumor primer. The nodule most often results from
contiguous extension of the tumor from the peritoneum, although lymphatic and venous
pathways likely contribute in some cases. Yang paling sering bintil hasil dari perpanjangan
berdekatan dari tumor dari peritoneum, meskipun jalur limfatik dan vena mungkin memberikan
kontribusi dalam beberapa kasus.

Sister Mary Joseph nodule in a patient with gastric carcinoma.

Suster Maria Joseph bintil pada pasien dengan karsinoma lambung. Note the shiny, reddish,
telangiectatic group of papules in the umbilicus. Perhatikan, mengkilap kemerahan, kelompok
telangiectatic papules di umbilikus.

As recognized by Sister Mary Joseph, the presence of the umbilical nodule is associated with
advanced intra-abdominal malignancies. Seperti yang diakui oleh Suster Maria Joseph, kehadiran
nodul pusar dikaitkan dengan keganasan intra-abdominal lanjut. Approximately 90% of these
malignancies are adenocarcinoma, with gastric and ovarian being the most commonly discovered
primary malignancy. Sekitar 90% dari keganasan yang adenokarsinoma, dengan keganasan
primer lambung dan ovarium yang paling sering ditemukan. Other cited primary sites include the
pancreas and bowel. Lain dikutip situs utama termasuk pankreas dan usus. Because the nodule is
so easy to biopsy and because most associated cancers are inoperable at the time of diagnosis,
the ability to identify this lesion may save a patient an unnecessary diagnostic surgery. Karena
bintil akar ini begitu mudah untuk biopsi dan karena kanker terkait kebanyakan dioperasi pada
saat diagnosis, kemampuan untuk mengidentifikasi lesi dapat menyimpan suatu pembedahan
diagnostik pasien yang tidak perlu. However, keep in mind that the biopsy will aid in
successfully diagnosing the primary site in only approximately half the cases. Namun, perlu
diingat bahwa biopsi akan membantu dalam berhasil mendiagnosis situs utama hanya kira-kira
setengah dari kasus.

Osler-Weber-Rendu syndrome (hereditary hemorrhagic telangiectasia) Osler-

Weber-Rendu syndrome (telangiectasia hemoragik herediter)

This autosomal dominant disorder occurs at a frequency of 1-2 cases per 10,000 population and
is characterized by vascular dilatations of the skin as well as the oral, nasal, and GI mucosa (see
the image below). [25, 26] First described by Babington in 1865 and further characterized by Rendu,
Osler, and Weber, the diagnosis is based on the presence of three of the 4 following criteria:
epistaxes, telangiectasia, visceral lesions, and an appropriate family history. [27] Gangguan ini
dominan autosom terjadi pada frekuensi 1-2 kasus per 10.000 penduduk dan ditandai oleh
dilatations vaskular kulit serta, hidung, dan GI mukosa oral (lihat gambar di bawah). [25, 26]
Pertama dijelaskan oleh Babington pada tahun 1865 dan selanjutnya ditandai dengan Rendu,
Osler, dan Weber, diagnosis didasarkan pada kehadiran tiga dari 4 kriteria berikut:,
telangiectasia, visceral, lesi dan tepat. sejarah keluarga epistaxes [27]

Arteriovenous malformations as seen on CT scan in a patient with

Osler-Weber-Rendu syndrome. malformasi arteriovenosa seperti yang terlihat pada CT scan
pada pasien dengan-Weber-Rendu sindrom Osler. The patches of hyperdensity within the liver
are the result of previous embolization procedures. Patch dari hyperdensity dalam hati adalah
hasil dari prosedur embolisasi sebelumnya.

The dermatologic examination reveals numerous 1- to 3-mm macular or papular, sharply

demarcated telangiectases on the face, lips, palate, tongue, ears, chest, or extremities, with
occasional presentation under nails. Pemeriksaan dermatologi menunjukkan banyak 1 - untuk 3-
mm makula atau papular, tajam ditandai telangiectases pada wajah, bibir, langit-langit mulut,
lidah, telinga, dada, atau kaki, dengan presentasi sesekali bawah kuku. The age of onset for the
telangiectases is most often the third decade of life, although earlier presentations may occur
during adolescence. Usia onset untuk telangiectases yang paling sering pada dekade ketiga
kehidupan, walaupun sebelumnya presentasi mungkin terjadi selama masa remaja. Although the
distribution of lesions and associated bleeding diathesis are clinically suggestive of hereditary
hemorrhagic telangiectasia, it may occasionally be difficult to distinguish from similar cutaneous
findings seen in generalized essential telangiectasia. Meskipun distribusi lesi dan diatesis
pendarahan yang berhubungan secara klinis sugestif dari telangiectasia hemorrhagic turun-
temurun, kadang-kadang mungkin sulit untuk membedakan dari temuan kulit serupa terlihat di
telangiectasia penting umum. Treatment of the dermatologic lesions involves electrosurgery or
laser therapy if warranted for cosmetic reasons. Pengobatan lesi dermatologi melibatkan terapi
elektrosurgikal atau laser jika diperlukan untuk alasan kosmetik.

The most common and often cardinal clinical manifestation of Osler-Weber-Rendu disease is
epistaxis, which generally starts in childhood and occurs in up to 80% of patients during their
lifetime. Manifestasi paling umum dan sering klinis utama penyakit Osler-Weber-Rendu adalah
epistaksis, yang umumnya dimulai di masa kecil dan terjadi pada sampai 80% dari pasien selama
hidup mereka. The epistaxis results from spontaneous bleeding from telangiectases of the nasal
mucosa and is generally recurrent. Para epistaksis hasil dari pendarahan spontan dari
telangiectases dari mukosa hidung dan umumnya berulang. In about one half of patients, the
frequency and seriousness of the epistaxis increases as the patient ages, leading to blood
transfusions in as many as 30% of patients. Dalam waktu sekitar satu setengah dari pasien,
frekuensi dan keseriusan meningkat epistaksis sebagai usia pasien, yang menyebabkan transfusi
darah sebanyak 30% dari pasien. Treatment with topical estrogen, laser therapy, and skin
grafting have been attempted to reduce the incidence of epistaxis. Pengobatan dengan estrogen
topikal, terapi laser, pencangkokan kulit dan telah dicoba untuk mengurangi kejadian epistaksis.

The second most common manifestation involves spontaneous hemorrhage from vascular
telangiectasia within the GI tract. [28, 29] The culprit lesions resemble the skin lesions in form and
size and most often are found in the stomach or the duodenum. Yang paling umum manifestasi
kedua melibatkan perdarahan spontan dari telangiectasia vaskular dalam saluran pencernaan. [28,
29]
Lesi pelakunya menyerupai lesi kulit dalam bentuk dan ukuran dan paling sering ditemukan di
perut atau duodenum. A ring of less vascularized tissue surrounding the GI lesions is a
characteristic finding on endoscopy. Sebuah cincin jaringan vascularized kurang sekitar lesi GI
adalah penemuan karakteristik pada endoskopi. Bleeding from these telangiectases tends to begin
in the fifth or sixth decade of life and often can be severe. Pendarahan dari telangiectases
cenderung mulai pada dekade kelima atau keenam hidup dan sering bisa parah. Treatment
modalities include endoscopic laser coagulation, bipolar electrocoagulation, surgical excision of
severely affected bowel segments, or medical management with low-dose combination
estrogen/progesterone or aminocaproic acid. modalitas pengobatan meliputi koagulasi laser
endoskopik, elektrokoagulasi bipolar, eksisi bedah dari segmen usus sangat mempengaruhi, atau
manajemen medis dengan kombinasi estrogen dosis rendah / asam progesteron atau
aminocaproic.

Another less frequent GI correlate is the presence of large arteriovenous malformations that can
develop within the liver, leading to substantial shunt formation. Lain berkorelasi GI lebih jarang
adalah adanya malformasi arteriovenosa besar yang dapat mengembangkan dalam hati, yang
menyebabkan terbentuknya shunt substansial. Although the prevalence of these lesions is
unknown, they have been blamed for portal hypertension with esophageal varices in some cases.
Meskipun prevalensi lesi ini tidak diketahui, mereka telah disalahkan untuk hipertensi portal
dengan varises esophagus dalam beberapa kasus. Diagnosis involves the presence of elevated
gamma-glutamyltransferase (GGT) or alkaline phosphatase levels, with confirmation by CT scan
or color Doppler ultrasound. Diagnosis melibatkan kehadiran ditinggikan-glutamyltransferase
gamma (GGT) atau tingkat fosfatase alkali, dengan konfirmasi oleh CT scan atau USG Doppler
warna. Treatment has tended to be conservative, with limited data on chemoembolization and
surgical ligation suggesting that both may be effective when therapeutic intervention is deemed
necessary. Pengobatan cenderung konservatif, dengan data terbatas pada Chemoembolization
dan ligasi bedah menyarankan bahwa keduanya mungkin efektif bila intervensi terapeutik
dianggap perlu.

Dermatology and the Liver and the Pancreas Dermatologi

dan Hati dan Pankreas yang
Hemochromatosis Hemochromatosis

Hemochromatosis is a disorder of iron overload leading to excess deposition in multiple body

organs. [30, 31] The hereditary form was first identified in the late 19th century as the classic triad
of glycosuria (diabetes), bronze skin pigmentation, and cirrhosis. Hemochromatosis adalah
gangguan dari kelebihan zat besi menyebabkan deposisi kelebihan di beberapa organ tubuh. [30, 31]
Bentuk keturunan pertama kali diidentifikasi pada abad ke-19 sebagai tiga serangkai klasik
glycosuria (diabetes), pigmentasi kulit perunggu, dan sirosis. The dermatologic manifestation of
the disease involves skin hyperpigmentation, which is present in more than 90% of patients at the
time of diagnosis. Manifestasi penyakit dermatologi melibatkan hiperpigmentasi kulit, yang
hadir di lebih dari 90% pasien pada saat diagnosis. This discoloration has a characteristic
metallic gray or bronze-brown color that is generally diffuse, but it may be increased in areas of
scars or on the face, neck, extensor surfaces of the arms, or genitalia. Perubahan warna ini
memiliki warna abu-abu atau perunggu-coklat metalik karakteristik yang umumnya menyebar,
tapi mungkin bisa meningkat di daerah bekas luka atau pada leher, wajah, permukaan ekstensor
lengan, atau alat kelamin. Approximately 20% of patients also have pigmentation of the buccal
mucosa or the conjunctiva. Sekitar 20% dari pasien juga memiliki pigmentasi mukosa bukal atau
konjungtiva.

Other characteristic skin findings in hemochromatosis include skin atrophy, ichthyosis, partial
hair loss (most often in the pubic region), and koilonychia. [32] The characteristic skin changes of
hemochromatosis are believed to result from increased melanin. Temuan kulit karakteristik
lainnya di hemochromatosis termasuk atrofi kulit, ichthyosis, hilangnya sebagian rambut (paling
sering di daerah kemaluan), dan koilonychia. [32] Perubahan karakteristik kulit hemochromatosis
diyakini hasil dari melanin meningkat. The actual presence of iron seen in dermal sweat glands
and the basal layer of the epidermis lead to the pigmentation seen in the late stages. Kehadiran
aktual dari besi terlihat pada kelenjar keringat kulit dan lapisan basal epidermis menyebabkan
pigmentasi terlihat pada tahap akhir. Treatment of these patients with phlebotomy or chelating
agents results in a decrease in skin pigmentation over time. Pengobatan pasien dengan proses
mengeluarkan darah atau chelating agen hasil dalam penurunan pigmentasi kulit dari waktu ke
waktu.

The most common GI finding in hemochromatosis is hepatomegaly, which is observed in more

than 95% of symptomatic patients. Temuan GI yang paling umum di hemochromatosis adalah
hepatomegali, yang diamati di lebih dari 95% pasien bergejala. Despite clinical findings of
functional liver impairment (eg, hair loss, gynecomastia, testicular shrinkage), laboratory
findings are generally unimpressive. Meskipun temuan klinis gangguan hati fungsional
(misalnya, rambut rontok, ginekomastia, penyusutan testis), temuan laboratorium umumnya
tidak mengesankan. Because hemochromatosis is not an inflammatory disease, liver enzyme (ie,
aspartate aminotransferase, alanine aminotransferase) levels can be normal, even in advanced
disease. Karena hemochromatosis bukan merupakan penyakit inflamasi, enzim hati (yaitu,
aspartat aminotransferase, alanine aminotransferase) tingkat bisa normal, bahkan dalam penyakit
lanjut. In patients with long-standing untreated hemochromatosis, cirrhosis may develop, leading
to hepatocellular carcinoma in as many as 30% of patients. Pada pasien dengan hemochromatosis
lama tidak diobati, sirosis dapat berkembang, menyebabkan karsinoma hepatoseluler di sebanyak
30% dari pasien. Cirrhosis or its complications account for approximately 89% of
hemochromatosis related deaths. Sirosis atau komplikasinya account untuk sekitar 89% dari
kematian hemochromatosis terkait.

Overall, patients with hereditary hemochromatosis have an estimated 5% annual risk for
hepatocellular carcinoma after the development of cirrhosis. Secara keseluruhan, pasien dengan
hemochromatosis keturunan memiliki risiko tahunan diperkirakan 5% untuk karsinoma
hepatoseluler setelah perkembangan sirosis. Primary treatment involves phlebotomy and
chelating agents, with conventional management of hepatic failure should this condition arise.
pengobatan primer melibatkan proses mengeluarkan darah dan agen pengkhelat, dengan
manajemen konvensional kegagalan hati harus kondisi ini muncul. A 1998 National Institutes of
Health consensus conference suggested weekly phlebotomy until serum ferritin concentration is
less than 50 mcg/L and transferrin saturation is less than 50%. Sebuah 1998 National Institutes of
konferensi konsensus Kesehatan menyarankan proses mengeluarkan darah mingguan sampai
serum feritin kurang dari 50 mcg / L dan saturasi transferin kurang dari 50%.

Porphyria cutanea tarda Porfiria cutanea tarda

Porphyria cutanea tarda is the most common porphyria occurring in adults, with a prevalence
ranging from 1 case in 5,000 to 1 case in 36,000 people. tarda cutanea Porphyria adalah porfiria
yang paling umum terjadi pada orang dewasa, dengan prevalensi berkisar dari 1 kasus pada
5.000 untuk 1 kasus dalam 36.000 orang. Cutaneous findings are characterized by skin
photosensitivity with increased skin fragility, facial hypertrichosis, blisters, scarring with milia
formation, and skin hyperpigmentation on the hands and other sun-exposed areas. Temuan
cutaneous dicirikan oleh photosensitivity kulit dengan kerapuhan kulit meningkat, hipertrikosis
wajah, lecet, luka dengan formasi milia, dan hiperpigmentasi kulit pada tangan dan daerah
terkena sinar matahari lainnya. Porphyria cutanea tarda results from the decreased activity of the
enzyme uroporphyrinogen decarboxylase (UROD), the fifth enzyme in the heme biosynthetic
pathway. Porfiria hasil tarda cutanea dari kegiatan penurunan dari dekarboksilase
uroporphyrinogen enzim (UROD), enzim kelima di jalur biosintesis heme.

The disease can be either sporadic or familial, but, in either case, it is clear that extrinsic factors
play an important role in producing a clinical manifestation of the disease. Penyakit ini dapat
bersifat sporadis atau keluarga, namun, dalam kasus lain, jelas bahwa faktor ekstrinsik
memainkan peran penting dalam memproduksi suatu manifestasi klinis dari penyakit.
Endogenous and exogenous factors (eg, alcohol, iron, estrogen, porphyrins, chronic hepatitis C
virus infection, polychlorinated biphenyls, polychlorinated cyclic hydrocarbons) produce
oxidative stress on the liver, leading to inhibition or decreased production of UROD. Endogen
dan faktor eksogen (misalnya, alkohol, besi, estrogen, porfirin, hepatitis C kronis infeksi virus,
poliklorinasi bifenil, polychlorinated hidrokarbon siklik) menghasilkan stres oksidatif pada hati,
menyebabkan penghambatan atau penurunan produksi UROD. The pathogenesis of iron in
porphyria cutanea tarda also provides the link to hereditary hemochromatosis. Patogenesis besi
di tarda porfiria cutanea juga menyediakan link untuk hemochromatosis keturunan. All patients
with porphyria cutanea tarda should undergo screening for the gene mutation identified in
hereditary hemochromatosis. [33, 34] Diagnosis involves the discovery of increased porphyrins in
the blood, liver, stool, and urine. Semua pasien dengan porfiria cutanea tarda harus menjalani
pemeriksaan untuk mutasi gen yang diidentifikasi dalam hemochromatosis keturunan. [33, 34]
Diagnosis melibatkan penemuan porfirin meningkat pada darah, hati, tinja, dan urin.

The first step of treatment involves the removal of possible triggers, including iron
supplementation, alcohol, and estrogens. Langkah pertama pengobatan melibatkan penghapusan
mungkin pemicu, termasuk suplemen zat besi, alkohol, dan estrogen. If symptoms persist,
repeated phlebotomy decreases the total iron load and leads to significant clinical improvement.
Jika gejala berlanjut, proses mengeluarkan darah diulang mengurangi beban besi total dan
menyebabkan perbaikan klinis yang signifikan. Phlebotomy may induce clinical remission,
reduce urinary porphyrins, and improve the sclerodermalike skin changes, but it is not proven to
improve liver histology. Proses mengeluarkan darah dapat menyebabkan remisi klinis,
mengurangi porfirin urin, dan meningkatkan perubahan kulit sclerodermalike, tetapi tidak
terbukti dapat meningkatkan histologi hati.

Other options include chloroquine and hydroxychloroquine, which form water-soluble

complexes with the porphyrins, facilitating their excretion in the urine. Pilihan lainnya terdiri
klorokuin dan hydroxychloroquine, yang membentuk kompleks larut air dengan porfirin,
memfasilitasi ekskresi mereka dalam urin. Antimalarial therapy can be quite dangerous in
patients with porphyria; it may precipitate massive hepatic injury. terapi antimalaria bisa sangat
berbahaya pada pasien dengan porfiria, tetapi dapat menimbulkan luka hati yang sangat besar.
Therefore, doses should be initiated at low doses (125 mg, 2-3 times per wk) to reduce the
likelihood of acute hepatic injury and retinopathy. Oleh karena itu, dosis harus dimulai dengan
dosis rendah (125 mg, 2-3 kali per minggu) untuk mengurangi kemungkinan cedera hati akut dan
retinopati. Such therapy should be attempted only when other therapy has failed and with a clear
understanding of the risks involved. terapi tersebut harus dicoba hanya bila terapi lain telah gagal
dan dengan pemahaman yang jelas tentang risiko terlibat.

The prevalence of hepatitis C in patients with PCT has been measured in series of patients from
many countries, with rates of as high as 85% in these patients. [35, 36] Interestingly, multiple
studies into the extrahepatic manifestations of patients with hepatitis C have failed to find an
increased rate of PCT. Prevalensi hepatitis C pada pasien dengan PCT telah diukur dalam
serangkaian pasien dari berbagai negara, dengan tingkat setinggi 85% pada pasien ini. [35, 36]
Menariknya, beberapa studi ke dalam manifestasi extrahepatic pasien dengan hepatitis C telah
gagal untuk menemukan tingkat peningkatan PCT. This disparity may be explained by the fact
that the background rate of PCT is relatively low in the populations in these latter studies and
that finding an association would require study of larger populations of patients. Kesenjangan ini
dapat dijelaskan oleh fakta bahwa tingkat latar belakang PCT relatif rendah dalam populasi
dalam studi ini yang terakhir dan yang menemukan hubungan akan memerlukan studi tentang
populasi yang lebih besar pasien.
The cause of the probable association between hepatitis C and PCT has been debated extensively
in the literature. Penyebab kemungkinan hubungan antara hepatitis C dan PCT telah
diperdebatkan secara luas dalam literatur. Some contend that hepatitis C serves to trigger attacks
of PCT in predisposed patients, but this theory remains to be conclusively proven. Beberapa
berpendapat bahwa hepatitis C berfungsi untuk memicu serangan PCT pada pasien cenderung,
tapi teori ini masih harus meyakinkan terbukti. Alternatively, others have hypothesized that
patients with PCT are somehow more susceptible to hepatitis C infection. Atau, yang lain
memiliki hipotesis bahwa pasien dengan PCT bagaimanapun lebih rentan terhadap infeksi HCV.
In either case, the probable linkage between these 2 diseases suggests that patients with PCT
should be tested for hepatitis C and that their treatment may be augmented by considering
concomitant therapy for hepatitis C. Dalam kedua kasus, kemungkinan hubungan antara 2
penyakit menunjukkan bahwa pasien dengan PCT harus diuji untuk hepatitis C dan bahwa
perlakuan mereka mungkin akan ditambah dengan terapi bersamaan mempertimbangkan untuk
hepatitis C.

Pancreatic fat necrosis Pankreas nekrosis lemak

First identified in 1883 by Chiari, the term pancreatic fat necrosis describes the association of
skin nodules with pancreatic disease. Pertama kali diidentifikasi pada tahun 1883 oleh Chiari,
nekrosis lemak istilah pankreas menggambarkan asosiasi nodul kulit dengan penyakit pankreas.
The dermatologic lesions can be painless or painful and tend to appear first on the legs followed
by the buttocks and trunk. [37] Initial presentation may include pruritus of lower extremities with
associated splotchy erythema. Lesi dermatologi dapat menimbulkan rasa sakit atau nyeri dan
cenderung muncul pertama pada kaki diikuti oleh pantat dan batang. [37] presentasi awal dapat
meliputi pruritus dari bawah kaki dengan eritema kotor terkait. Progression to a nodular
component is associated with tenderness. Pengembangan menjadi komponen nodular dikaitkan
dengan kelembutan. Nodules, usually no more than 30, have been described to spontaneously
drain white creamy exudate, after which the lesion heals with hyperpigmentation and local scar
formation. Nodul, biasanya tidak lebih dari 30, telah dijelaskan secara spontan menguras eksudat
krem putih, setelah menyembuhkan luka dengan formasi parut hiperpigmentasi dan lokal. The
pathologic correlate includes the presence of subcutaneous fat necrosis together with ghostlike
calcified fat cells containing thick shadowy walls and no nucleus. Ini berkorelasi patologis
termasuk adanya nekrosis lemak subkutan bersama-sama dengan hantu sel-sel lemak yang
mengandung kalsifikasi dinding bayangan tebal dan tidak ada inti.

The presence of these fluctuant lesions on the skin surface has been used to identify underlying
pancreatic disease. [38, 39] Often, it is the skin eruption that leads the patient to medical care in the
first place. Keberadaan lesi ini berfluktuasi pada permukaan kulit telah digunakan untuk
mengidentifikasi penyakit pankreas yang mendasari. [38, 39] Sering kali, itu adalah erupsi kulit
yang menyebabkan pasien untuk perawatan medis di tempat pertama. Pancreatic fat necrosis
occurs in up to 65% of patients with pancreatic cancer and in up to 22% of patients with
pancreatitis. Pankreas nekrosis lemak terjadi di hingga 65% pasien dengan kanker pankreas dan
pada sampai dengan 22% dari pasien dengan pankreatitis. More than half the patients with
pancreatic cancer–associated subcutaneous fat necrosis have the acinar form. [40] The presence of
subcutaneous fat necrosis along with pancreatic disease is a poor prognostic indicator; one series
of 27 patients demonstrated that all 8 patients with associated pancreatic carcinoma and 8 of the
19 patients with pancreatitis died as a result of their disease. Lebih dari separuh pasien dengan
pankreas terkait nekrosis lemak subkutan kanker memiliki bentuk asinar. [40] Kehadiran nekrosis
lemak subkutan bersama dengan penyakit pankreas adalah indikator prognosis yang buruk; satu
rangkaian dari 27 pasien menunjukkan bahwa semua 8 pasien dengan terkait pankreas karsinoma
dan 8 dari 19 pasien dengan pankreatitis meninggal sebagai akibat dari penyakit mereka.

The development of subcutaneous nodules in cases of pancreatic disease may derive from the
release of pancreatic lipolytic enzymes, a hypothesis confirmed by the biochemical discovery of
persistently elevated serum lipase and trypsin levels 100-fold in one case report. Perkembangan
nodul subkutan dalam kasus penyakit pankreas mungkin berasal dari pelepasan enzim lipolitik
pankreas, hipotesis dikonfirmasi oleh penemuan biokimia lipase serum terus-menerus tinggi dan
tingkat tripsin 100 kali lipat dalam satu laporan kasus. The relief of pancreatic insult by
endoscopic retrograde cholangiopancreatography (ERCP) in another recent case report not only
halted serum amylase release but also resolved the symptoms of panniculitis. [41] Relief
penghinaan pankreas oleh Kolangiopankreatografi retrograd endoskopik (ERCP) dalam laporan
lain kasus baru-baru tidak hanya terhenti rilis amilase serum tetapi juga memutuskan gejala
panniculitis. [41]

Lichen planus Lichen planus

Lichen planus is an idiopathic inflammatory disorder of the skin and mucous membranes known
to be associated with a variety of liver diseases. Lichen planus merupakan gangguan inflamasi
idiopatik pada kulit dan selaput lendir diketahui terkait dengan berbagai penyakit hati. The skin
lesions are purple, polygonal, flat-topped papules that are usually pruritic. Lesi kulit berwarna
ungu, polygonal, datar papules yang biasanya pruritic. A characteristic finding on close (through
a lens) examination is the presence of white or gray linear markings known as Wickham striae.
Temuan karakteristik di dekat (melalui lensa) pemeriksaan adalah adanya tanda-tanda linier
putih atau abu-abu dikenal sebagai striae Wickham. They may be found anywhere on the skin,
although certain sites, such as the wrists, ankles, shins, lower back, and genitalia, are most
commonly affected. Mereka mungkin ditemukan di mana saja pada kulit, meskipun situs
tertentu, seperti pergelangan tangan, pergelangan kaki, tulang kering, punggung bawah, dan alat
kelamin, yang paling sering terkena.

The mucous membranes also are affected quite frequently [42] and sometimes are the only site
involved. Selaput lendir juga terkena dampak cukup sering [42] dan kadang-kadang adalah situs
hanya terlibat. The lesions are most frequently white reticulated papules that form a lacelike
pattern. Lesi yang paling sering papula reticulated putih yang membentuk pola lacelike. Both
cutaneous and oral lesions exhibit Köbner phenomenon, occurring at sites of previous trauma,
leading to oral lesions on buccal mucosa and lateral surfaces of the tongue. Baik lesi kulit dan
oral menunjukkan fenomena Köbner, terjadi di situs dari trauma sebelumnya, mengarah ke lesi
oral pada mukosa bukal dan permukaan lateral lidah. Nail dystrophy is common, including the
presence of pterygia and longitudinal ridges. distrofi kuku adalah umum, termasuk keberadaan
pterygia dan longitudinal pegunungan. Treatment for both the skin and mucous membrane
lesions involves the use of local or systemic steroids, specially formulated oral preparations of
topical immunomodulators and systemic immunosuppressives for treatment-resistant cases to
include thalidomide, azathioprine, mycophenolate mofetil, and systemic retinoids. Pengobatan
untuk lesi membran baik pada kulit dan mukosa melibatkan penggunaan steroid lokal atau
sistemik, diformulasikan khusus persiapan oral Immunomodulators topikal dan sistemik
immunosuppressives untuk kasus pengobatan-tahan untuk memasukkan thalidomide,
azathioprine, mycophenolate mofetil, dan retinoid sistemik. Almost two thirds of patients have
spontaneous remission of the skin lesions within 1 year. Hampir dua pertiga dari pasien memiliki
remisi spontan dari lesi kulit dalam waktu 1 tahun.

The pathogenesis of lichen planus is not clear, but several authors have postulated an association
with both primary biliary cirrhosis (PBC) and chronic hepatitis B and C. [43, 44, 45, 46, 47, 48, 49] The
association of PBC is particularly compelling because both diseases involve immunopathologic
mechanisms that are not yet fully understood. Patogenesis lichen planus tidak jelas, tetapi
beberapa penulis telah didalilkan asosiasi dengan baik primary biliary cirrhosis (PBC) dan kronis
hepatitis B dan C. [43, 44, 45, 46, 47, 48, 49] Asosiasi PBC sangat menarik karena kedua penyakit
melibatkan mekanisme immunopathologic yang belum sepenuhnya dipahami. However, not all
authors have agreed that these associations occur at any more than the expected random
frequency. Namun, tidak semua penulis telah sepakat bahwa asosiasi ini terjadi pada lebih dari
frekuensi acak yang diharapkan. Precipitating factors for oral lesions include mechanical trauma
from dental procedures and dental prostheses, heat and irritation from tobacco products, and oral
habits to include lip and cheek chewing. faktor pengendapan untuk lesi oral termasuk trauma
mekanik dari prosedur gigi dan prostesis gigi, panas dan iritasi dari produk tembakau, dan
kebiasaan oral untuk memasukkan bibir dan pipi mengunyah.

Dermatology and the Small Intestine Dermatologi dan Usus

Kecil
Peutz-Jeghers syndrome Peutz-Jeghers sindrom

An autosomal dominant disorder affecting approximately 1 in 10,000 live births, Peutz-Jeghers

syndrome (PJS) is characterized by the presence of mucocutaneous hyperpigmentation together
with GI polyposis. Gangguan dominan autosomal mempengaruhi sekitar 1 dari 10.000 kelahiran
hidup, Peutz sindrom-Jeghers (Pjs) ditandai dengan adanya hiperpigmentasi mukokutan
bersama-sama dengan poliposis GI. Clinical diagnosis requires histologic identification of
intestinal hamartomatous polyps in conjunction with 2 of 3 additional clinical criteria that
include small bowel polyposis, mucocutaneous melanotic pigmentation, and a family history of
PJS. diagnosis klinis memerlukan identifikasi histologis hamartomatous polip usus bersama
dengan 2 dari 3 kriteria klinis tambahan yang mencakup poliposis usus kecil, pigmentasi
melanotic mukokutan, dan sejarah keluarga Pjs. The skin findings first appear in infancy or early
childhood and involve blue-brown macular lesions of 1-10 mm. Temuan kulit pertama kali
muncul pada masa bayi atau anak usia dini dan melibatkan lesi makula biru-coklat 1-10 mm. The
lesions most commonly are found on the lips (95% of patients) [50] and buccal mucosa (83%).
Lesi yang paling sering ditemukan pada bibir (95% dari pasien) [50] mukosa bukal dan (83%).
Other frequently affected sites include the palms of the hands, fingers, nose, gingiva, eyelids, and
hard palate. Situs sering terkena lainnya meliputi telapak, jari-jari tangan, hidung, gingiva,
kelopak mata langit-langit, dan keras. Over time, the mucosal lesions tend to persist, while the
cutaneous lesions fade away. Seiring waktu, lesi mukosa cenderung bertahan, sedangkan lesi
kulit memudar. Ruby and argon lasers have been used successfully to eradicate the mouth
pigmentation. Ruby dan laser argon telah berhasil digunakan untuk membasmi pigmentasi mulut.

GI manifestations of PJS involve the presence of multiple hamartomatous polyps occurring most
commonly in the jejunum (see the image below). GI manifestasi dari Pjs melibatkan kehadiran
polip beberapa hamartomatous terjadi paling sering di jejunum (lihat gambar di bawah). Other
sites include the stomach, duodenum, ileum, and colon. Situs lain termasuk perut, duodenum,
ileum, dan usus besar. Symptoms may include abdominal pain, bleeding, rectal prolapse, or
obstruction due to intussusception. Gejala termasuk sakit perut, perdarahan, prolaps rektum, atau
obstruksi karena intussusception. In addition, 2-3% of patients develop GI carcinoma during
their lifetimes, a frequency that has led to the recommendation of upper and lower endoscopy
every 2 years in patients with PJS, with removal of all large polyps. [51, 52] Selain itu, 2-3% pasien
berkembang karsinoma GI selama hidup mereka, frekuensi yang telah menyebabkan
rekomendasi dari atas dan bawah endoskopi setiap 2 tahun pada pasien dengan Pjs, dengan
penghapusan semua polip besar. [51, 52]

Multiple large intestinal polyps in a patient with Gardner

syndrome. Beberapa polip usus besar pada pasien dengan sindrom Gardner. Courtesy of
Christina Surawicz, MD, Harborview Medical Center, Seattle, Wash. Courtesy of Surawicz
Christina, MD, Medical Center Harborview, Seattle, Washington

Care of these patients also involves regular surveillance for cancers involving the breast, ovary,
testicle (Sertoli cell testicular tumors, leading to associated gynecomastia), cervix, thyroid, and
other tissues. [53] These recommendations are supported by a recent long-term cohort study of 34
patients with PJS that demonstrated both a disproportionate number of noncutaneous cancers (26
cases, 16 non-GI tract, relative risk 9.9) and an unusually young age of diagnosis of these
carcinomas (average age 39.4 y). Perawatan pasien ini juga melibatkan pengawasan rutin untuk
kanker yang melibatkan payudara, ovarium, testis (testis tumor sel Sertoli, menyebabkan
ginekomastia berhubungan), leher rahim, tiroid, dan jaringan lain. [53] Rekomendasi ini didukung
oleh baru-baru ini jangka panjang kohort studi dari 34 pasien dengan Pjs yang menunjukkan baik
jumlah yang tidak proporsional dari kanker noncutaneous (26 kasus, 16 non-GI saluran, risiko
relatif 9,9) dan usia muda yang luar biasa diagnosis karsinoma ini (umur rata-rata 39,4 y).
Patients with a clinical diagnosis of PJS should have ongoing surveillance of all these organ
systems. Pasien dengan diagnosis klinis Pjs harus memiliki pengawasan yang berkelanjutan dari
semua sistem organ.
Henoch-Schönlein purpura Purpura Henoch-Schönlein

This small vessel vasculitis manifests clinically by the syndrome of palpable purpura, arthralgias,
abdominal symptoms, and glomerulonephritis. [54, 55] Males are affected twice as frequently as
females, with an overall incidence of 14 cases per 100,000 population. Vaskulitis kapal kecil ini
memanifestasikan klinis oleh sindrom purpura teraba, arthralgias, gejala-gejala perut, dan
glomerulonefritis. [54, 55] Pria yang terkena dua kali lebih sering sebagai perempuan, dengan
kejadian keseluruhan 14 kasus per 100.000 penduduk. The diagnosis usually is made in early
childhood, but it also can present in infancy or adulthood. [56] The disease is believed to be due to
the deposition of immunoglobulin A (IgA)–mediated immune complexes throughout the body.
Diagnosis biasanya dilakukan pada anak usia dini, tetapi juga dapat hadir pada masa bayi atau
dewasa. [56] Penyakit ini diyakini karena pengendapan imunoglobulin A (IgA) kekebalan
kompleks dimediasi-seluruh tubuh. A variety of triggers for this process have been proposed,
including insect bites, seasonal allergens, upper respiratory tract infections, various medications,
and foods. Berbagai pemicu proses ini telah diusulkan, termasuk gigitan serangga, alergi
musiman, infeksi saluran pernapasan bagian atas, berbagai obat-obatan, dan makanan.

The skin abnormalities are present in all patients at some point in their disease process and
involve the presence of palpable purpuric lesions found most commonly on the buttocks and
legs. The lesions may appear in groups and may be vesicular or ulcerating in some cases.
Definitive diagnosis can be obtained through direct immunofluorescence of early lesions (aged <
24 h), revealing a perivascular deposition of IgA. Renal findings in patients with this disease
include glomerulonephritis with the presence of proteinuria, microscopic hematuria, and often
red cell casts. Musculoskeletal pain can be diffuse and severe in some cases, although less than
20% of patients initially present with this symptom. Adults, in comparison to children, seem to
more commonly present with symmetric arthralgias and arthritis of knees and ankles.

Gastroenterologic symptoms, which are found in more than 50% of patients with Henoch-
Schönlein purpura, include colicky abdominal pain, diarrhea/constipation, occult or occasionally
overt bleeding, and rarely intussusception or perforation. [57] These symptoms may appear
simultaneously with the skin lesions, or they may appear several days to weeks earlier.
Endoscopic evaluation may demonstrate marked generalized redness, raised lesions, multiple
ulcerations, or diffuse erosive lesions. [58]

A recent retrospective study aimed at determining the distribution of GI involvement in 7

patients with Henoch-Schönlein purpura found the duodenum and small intestine to be the most
frequently involved sites. The natural course of the disease is complete resolution over weeks to
months. However, the presentation of Henoch-Schönlein purpura differs significantly with age;
older patients exhibit much more severe renal and extrarenal manifestations than younger
patients. The use of corticosteroids has been reported to be helpful in reducing the GI symptoms,
although no placebo-controlled trials have been performed to demonstrate a clear benefit. A
reasonable management strategy involves a short (1 wk) course of steroids in patients with
severe discomfort. [59]

Dermatitis herpetiformis Dermatitis herpetiformis

This uncommon blistering disorder is characterized by the development of small vesicular
lesions found in a symmetric distribution of both upper and lower extensor surfaces and the
scalp. First described in 1884 by Louis Duhring, MD, the usual age of onset of dermatitis
herpetiformis is in the third decade of life. Most patients experience severe pruritus as a result of
the skin lesions, although some are almost completely asymptomatic. Pruritus can lead to
significant excoriation and secondary changes, leading to misdiagnosis of atopic dermatitis. The
characteristic direct immunofluorescence finding is granular deposition of IgA within the dermal
papillae on direct immunofluorescence. Patients may have elevated serum IgA antibodies against
transglutaminase 2 and 3. [60]

In patients with dermatitis herpetiformis, 20% have a clinically overt celiac disorder while
almost 100 percent of patients with dermatitis herpetiformis have demonstratable pathologic
changes of celiac disease on small intestinal biopsy. [61, 62] Indeed, both dermatitis herpetiformis
and celiac disease have been found to share class II HLA allele sites in recent immunogenetic
studies, a finding confirmed clinically by case reports of monozygotic twins afflicted by both
diseases.

The clinical manifestations of the celiac disease (also known as gluten-sensitive enteropathy and
celiac sprue) are caused by the inability to absorb gluten from the diet. Patients experience
weight loss, diarrhea, bloating, and steatorrhea. Chronic problems with malabsorption eventually
may lead to iron or folate-deficient anemia states. Therapy involves the adoption of a gluten-free
diet, with avoidance of foods such as wheat, barley, and rye. The initiation of therapy with
dapsone or sulfapyridine results in a dramatic improvement in both GI and dermatologic
symptoms; a prompt improvement following therapy can confirm the diagnosis.

Blue rubber bleb nevus syndrome Blue karet lepuh sindrom nevus

This rare disorder is characterized by the combination of cutaneous vascular malformations and
GI bleeding due to the presence of vascular malformations. [63, 64] A clinical syndrome first
described by Bean in 1958, transmission may be sporadic or autosomal dominant. The clinical
manifestations most often present in birth or early childhood, although some cases may not be
identified until adulthood. The skin lesions can number from 1 to more than 100 and may come
in 3 forms:

 Nontender soft nodules that when compressed leave behind a blue empty sac that refills
rapidly with blood (blue rubber nipple)
 Blue-black punctate tender macular lesions widely distributed on the extremities and
trunk
 Large hemangiomas (up to 10 cm in diameter) that may interfere with important limb or
organ function

The GI manifestations of the blue rubber bleb nevus syndrome involve the presence of vascular
malformations found most frequently in the small intestine and colon (although lesions have
been identified in the mesentery, lung, liver, eye, and CNS.) The malformations project into the
gut lumen and resemble the nodular skin lesions in appearance. Clinically, these malformations
usually cause occult bleeding, although frank melena, hematochezia, or even intussusception
may occur. The treatment is largely dependent upon the extent of the disease course; for mild
blood losses over time, therapeutic intervention can involve monitoring, iron replacement, and
blood transfusions when needed. In severe cases, treatment may require endoscopic therapy with
bipolar electrocautery or YAG laser, or even surgical resection of affected areas.

Dermatology and the Large Intestine

Familial adenomatous polyposis (Gardner syndrome)

Gardner syndrome describes an autosomal dominant disorder involving the triad of epidermal
cysts, osteomas, and adenomatous GI polyposis. [65] Originally described by Gardner in 1953, the
disease is now known to involve a single gene defect on chromosome 5. [66] The epidermal cysts
are found in more than 50% of patients and tend to appear in decreasing likelihood of occurrence
on the lower extremities, face, scalp, and upper extremities. The age of onset is the early teenage
years, and they are almost always multiple. Cutaneous cysts frequently predate intestinal polyps.
Osteomas, located most frequently in the mandible or maxilla, occur in at least 75% of patients
with Gardner syndrome. Other associated findings include desmoid tumors (visceral and
nonvisceral types), pilomatricomal cysts, dental abnormalities, and pigmented ocular fundal
lesions termed congenital hypertrophy of the retinal epithelium.

The GI manifestation of Gardner syndrome involves the presence of adenomatous polyps, which
are believed to occur in 100% of patients at some point in their lifetime. The polyps are first
noted at an average age of 22 years and tend to occur in large numbers (>100) in any part of the
colon. These lesions, which also can be found in the duodenum around the ampulla of Vater,
eventually progress to carcinoma in almost all patients if left untreated. Therapy involves regular
colonoscopy and excision of polyps.

Muir-Torre syndrome

As another autosomal dominant disorder with variable expressivity, the Muir-Torre syndrome
(MTS) also links abnormal skin findings with colonic malignant potential. [67] Described
separately by Muir and Torre in 1967, the syndrome associates sebaceous neoplasms with an
increased propensity for colorectal carcinoma. The defect has been attributed to a DNA
mismatch repair gene mutation, a discovery that now allows physicians to screen relatives of
affected patients. The skin findings in Muir-Torre syndrome are a diverse lot, including
sebaceous neoplasms such as adenoma, epithelioma, carcinoma, basal cell carcinoma with
sebaceous cell differentiation, and keratoacanthomas. [68]

Unlike the universal presence of polyps in Gardner syndrome, patients with Muir-Torre have
colonic polyposis in only approximately half the cases. However, visceral malignancies develop
in a large proportion of patients, most frequently in the colon (51% of all primary tumors). Other
sites of carcinoma include the larynx, duodenum, ileum, stomach, uterus, ovary, ureter, kidney,
and bladder. The malignancies associated with MTS tend to be less aggressive than those
unassociated with the syndrome, leading to a better prognosis than one might otherwise suppose
given the malignancy. Treatment of patients with MTS involves regular screening for GI and
genitourinary cancers.
Cowden disease (multiple hamartoma syndrome)

Cowden disease is a rare disease of autosomal dominant inheritance that is characterized by

hamartomas of various tissues. Dermatologic findings include trichilemmomas (ie, skin colored
papules around facial orifices), acral keratoses, and oral papillomas. The disease is associated
with a variety of malignancies, including breast, thyroid, endometrial, cervical, and colon cancer.

GI polyposis occurs in at least 35% of patients with Cowden disease, a figure that may be an
underestimate because of incomplete endoscopic examination in many patients. The most
common sites of polyposis are the colon and rectum, although polyps have been documented in
the esophagus, stomach, gallbladder, and small bowel.

A review of the 67 patients with Cowden disease who have undergone endoscopic evaluation
over the past 30 years [69] demonstrates that most polyps discovered are nonadenomatous,
although approximately 24% were adenomatous. Of particular concern are the 12 patients (18%)
who had adenomatous colonic and rectal polyps, an established risk factor for colorectal cancer.
Although the precise risk of colon cancer in patients with Cowden disease has not been firmly
established, all patients should receive a thorough initial GI workup with follow-up care as
appropriate.

Cronkhite-Canada syndrome Cronkhite-Kanada sindrom

This tetrad of diffuse macular hyperpigmentation, alopecia, nail atrophy, and GI polyposis
initially was described in 2 patients by Cronkhite and Canada in 1952. [70] This extremely rarely
identified syndrome has been further defined with the collection of more than 50 cases from the
literature. The average age of onset is 59, with a range of ages of 31-86 years. The
hyperpigmented macules and plaques (85% of patients) most often occur on the upper
extremities but may be diffusely distributed. Nail dystrophy (affecting 90% of patients) is seen in
all fingers and toes and is characterized by onycholysis and a unique pattern of normal nail in the
shape of an inverted triangle that borders up against dystrophic nail. The alopecia (>95% of
patients) described with this disease is of rapid onset, with progression from patchy hair loss to
eventual complete loss of hair. [71]

GI symptoms include diarrhea, significant weight loss, and abdominal pain. The presence of
hamartomatous polyps is quite common, with transformation to malignancy occurring in some
cases.

Cronkhite-Canada syndrome is fatal in about one half of patients, usually as a result of

malnutrition or persistent diarrhea. Therapy involves nutritional support and careful observation
for metabolic derangements over the course of the illness. [72] One case report noted a temporal
association with the initiation of ranitidine therapy and resolution of clinical symptoms in one
patient, although the mechanism of response to therapy in this patient is unclear.

Bannayan-Riley-Ruvalcaba syndrome Bannayan-Riley-Ruvalcaba sindrom

This is a rare autosomal dominant genodermatosis with classic triad of macrocephaly, genital
lentiginosis, and intestinal polyposis. Given overlap with Cowden syndrome with phenotypic
expression and similar allelic syndromes (both with identical PTEN mutations), both diseases are
collectively referred to as PTEN hamartoma-tumor syndrome. Mucocutaneous findings include
vascular malformations, lipomatosis, speckled lentigines of the penis and vulva, facial acanthosis
nigricanslike lesions, and multiple acrochordons.

Similarly to Cowden disease, patients can have prominent diffuse hamartomatous polyposis and
vascular lipomatous hamartomas manifesting as tender or painful, rapidly enlarging, aggressive
subcutaneous and/or visceral lesions. Prominent hamartomatous polyposis occurs in 35-45% of
cases of Bannayan-Riley-Ruvalcaba syndrome but is not associated with an increased risk of
malignancy. Polyps can be located anywhere along the GI tract, with a preference for colonic or
rectal localization. Presentation of polyposis may not manifest until middle age, requiring routine
follow-up visits with a yearly hemoglobin test and fecal occult blood test. During childhood,
symptoms include massive watery diarrhea, abdominal pain, painless rectal bleeding, and
chronic anemia. The size of the polyps can be quite large, leading to intussusception and
intestinal obstruction.

Inflammatory bowel disease Radang usus

Both Crohn disease (CD) and ulcerative colitis (UC) bring with them a considerable host of
dermatologic findings. Since there is a large amount of overlap in these findings, the diseases
will be considered together in this discussion. CD is characterized clinically by symptoms of
fever, abdominal pain, fatigability, and diarrhea that may or may not be bloody. The disease
most often is diagnosed in patients aged 15-35 years, although it has been described in people of
all ages.

Histologically, the inflammatory lesions of CD extend through all layers of the gut lining and
may extend into the mesentery or local lymphatics. The disease may appear in all areas of the GI
tract from the mouth [73] to the anus and often is characterized by skip lesions, areas of the bowel
that are completely free of inflammation. Although UC affects patients in similar age groups, this
disease is more likely to result in bloody diarrhea and abdominal distension. The pathologic
appearance of this disease demonstrates continuous colonic involvement from the rectum to the
junction with the terminal ileum, with the inflammation confined to the mucosal layer. Diagnosis
of both diseases generally is made easily with a combination of sigmoidoscopy and barium-
assisted radiologic studies.

Cutaneous manifestations of inflammatory bowel disease are quite common, with various studies
suggesting skin involvement in 9-19% of patients with UC and 9-40% in patients with CD. The
most common skin findings are described below.

 Fissures: Although infrequent phenomena in patients with UC, fissures of the skin in
patients with CD are often quite uncomfortable. The most common area is the perineum,
with particular involvement of the perianal area. The National Cooperative Crohn's
Disease study demonstrated that patients with colonic involvement are significantly more
likely to have perianal fissures than those with CD affecting other areas of bowel (40%
 compared to 25%). As with other patients with perianal fissures, treatment with topical
nitroglycerin or injected botulinum toxin can be quite effective.
 Oral lesions: Mouth findings of patients with CD include findings such as angular
cheilitis, aphthous ulceration, or mucosal cobblestoning. Metastatic CD lesions on skin or
mucosa can show sarcoid-type granulomas on histology and can correlate with disease
activity. One study found an incidence of oral findings in patients with CD of
approximately 0.5%, and the long-term follow-up care of these patients indicated that the
clinical course of the oral lesions can be quite lengthy. Treatment with topical
corticosteroids did result in some symptomatic improvement in these patients.
 Pyoderma gangrenosum: Found in approximately 5% of patients with UC and about 1%
of those with CD, pyoderma gangrenosum describes a painful, ulcerative lesion with a
well-defined, elevated, dusky border (see the image below). The lesions start as small
pustules, which subsequently burst and expand to form the larger noninfectious ulcer.
Although some patients with pyoderma gangrenosum are not found to have an underlying
disease, the disease has been associated with myeloma, rheumatoid arthritis, and

leukemias in addition to inflammatory bowel diseases.

Pyoderma gangrenosum. Note the rolled-up, edematous, and undermined border with the
surrounding halo of bright-red erythema. The base of the ulcer contains a fibrinopurulent
exudate. This ulcer evolved from a "pimple" over a period of just a few weeks.
 Approximately 50% of patients with pyoderma gangrenosum eventually are found to
have UC, although the disease may be subclinical at the time of appearance of the skin
lesion. For this reason, an evaluation of the colon should be undertaken in all patients
with the skin findings. Treatment of the inflammatory bowel disease or other underlying
causative illness may lead to an improvement in the skin lesions. Some patients require
systemic treatment with oral corticosteroids or cyclosporine. Chronic ulcers may respond
to topical sodium cromoglycate.
 Erythema nodosum: This relatively common dermatologic finding presents as tender,
nonulcerative, red nodules found most frequently on the lower legs. Histologically, the
lesions are characterized by septal panniculitis. Erythema nodosum is associated with a
variety of conditions, including medications, malignancy, and infections. In one large
series of patients, 7% of patients with UC had erythema nodosum, with a less frequent
association in CD.