A 38 year old man with a 15 year history of Crohn's disease developed an 8 x 5 cm plaque on the right
buttock that was not in continuity with diseased anal or rectal mucosa. A biopsy showed a psoriasiform
pattern of epidermal hyperplasia overlying dilated dermal lymphatic spaces containing aggregates of banal
Case 3 - Figure 1 - There is a plaque on the left buttock, some 8x5 cm in diameter. It is not in continuity with the anal canal.
Case 3 - Figure 2 - The biopsy shows psoriasiform hyperplasia overlying markedly dilated dermal lymphatic spaces.
Case 3 - Figure 3 - The dilated lymphatic spaces contain clusters of endovascular histiocytes.
Case 3 - Figure 4 - The dilated lymphatic spaces contain clusters of endovascular histiocytes.
This is a patient of Dr Michael Wilkerson, Tulsa OK, who kindly provided clinical photographs.
Cutaneous Crohn's disease with psoriasiform dermatitis and endovascular histiocytopathy.
Introduction and Clinical Features
Skin lesions occur in 14 to 44% of patients with Crohn's disease (CD)
erythema nodosum (EN) , pyoderma gangrenosum (PG)
, bowel dermatosis-arthritis
syndrome , periorificial pyoderma , pyoderma faciale , sterile
neutrophilic folliculitis with perifollicular vasculitis , and so-called "metastatic"
CD  which comprises non-necrotizing sarcoid-like granulomatous dermatitis. 
The pathogenetic mechanism by which skin lesions develop in CD patients is enigmatic. Animal models
suggest that microbial pathogens may play a role in producing the gut and skin lesions of
Some case reports relate CD directly to infection by Mycobacterium avium subspecies paratuberculosis  for which
antimicrobial therapy can be curative. Other implicated microbes include viruses such as
paramyxovirus and measles virus , and other bacteria such as Listeria monocytogenes, Yersinia sp. Helicobacter sp, Escherichia
coli, and Chlamydia sp..  Elevated levels of anti-Saccharomyces cerevisiae antibodies (ASCA's), described in sera of adult CD
patients , dissappear with resection of the diseased bowel. In contrast to perinuclear
anti-nuclear cytoplasmic antibody (pANCA), which appears to identify a subset of CD patients with a
UC-like presentation, the ASCA antibodies appear not to be autoantibodies but are instead directed
against oligomannosidic epitopes common to various microbial species;
tolerance to gut microbes is postulated. 
We hypothesized that the skin lesions might be due to hematogenous dissemination of colonic
bacteria.  In this regard, the mucosal lesions of CD may reflect direct bacterial infection
as enteric microflora induce persistent antigenic stimulation in the genetically susceptible host or,
alternatively, persistent low-grade bacterial intracellular colonization of macrophages in the lamina
propria could evoke the inflammatory cascade leading to active enteritis. Held to support
this concept is the identification by polymerase chain reaction (PCR) of the 16S rRNA gene, highly
conserved among bacteria, in the inflammatory lesions of CD.
Using an RT in situ PCR
method to enable direct localization of the bacteria in tissue specimens, we demonstrated the presence
of intracellular bacteria in the colonic lamina propria of people with active colitis, a finding that
suggests that intracellular bacteria are directly associated with pathogenesis. Conversely, we failed
to demonstrate consensus bacterial 16S rRNA in the corresponding skin biopsies from these patients, a
finding that effectively excludes a colonic bacterid as the pathogenetic basis of skin lesions in CD and
implies that there is an alternative mechanism in their propagation. The cutaneous
manifestations may reflect an excessive immunologic response to nonviable bacterial protein fragments or
to homologous epitopes in the dermal microvasculature or stroma. This could explain, at least in part,
the temporal association of the cutaneous eruptions with the exacerbation of colitis and their
improvement and/or resolution with treatment.
In our hands, the following cutaneous lesions are most common in CD patients:
1: Palisading granulomatous dermatitis with features of granuloma annulare and
necrobiosis lipoidica - comprising superficial and deep dermal interstitial and palisading
histiocytic infiltrates with variable necrobiosis, venulitis of granulomatous and/or neutrophilic
subtypes, and extravascular neutrophilia
2: Sterile neutrophilic folliculitis with perifollicular vasculopathy,
- manifesting either a purely granulomatous or purely neutrophilic folliculitis, with variable
follicular necrosis and perifollicular vasculitis of either leukocytoclastic and/or granulomatous
subtypes in the setting of special stains negative for bacteria and fungi.
3: Dominantly neutrophilic infiltrates (ie neutrophilic dermatoses including
pyoderma gangrenosum (PG)) - comprising papillary dermal edema with neutrophilic and mononuclear
cell infiltrates localized to vessels showing erythrocyte extravasation absent fibrin deposition, ie
"Sweet's syndrome-like vasculopathy". Other cases are typical of PG by virtue of neutrophilic
infiltration of the dermis with disintegration of the connective tissue fiber network (neutrophilic
dermolysis) with a Sweet's-like vascular reaction. An important clue is the presence of scattered
multinucleated giant cells in the zones of neutrophilic infiltration, a feature previously reported as
being characteristic of PG lesions in patient with CD.  One occasionally sees
pseudoepitheliomatous hyperplasia and intraepithelial pustulation. The term pyostomatitis vegetans has been applied to such lesions in continuity with
diseased rectal or oral mucosa.
4: Panniculitis - comprising infiltration of the interstices of the fat
lobules by neutrophils and mononuclear cells with minimal leukocytoclasia; some cases have concomittant
pandermal vasculitis of granulomatous and leukocytoclastic types with lymphocytic eccrine hidradenitis.
We have also seen a septal fibrosing and neutrophilic panniculitis compatible with EN but with prominent
5: Non-folliculocentric vasculitis - usually a granulomatous vasculitis
whereby the superficial vascular plexus contains thrombi unaccompanied by inflammation or a pan-dermal
6: Lichenoid and granulomatous dermatitis - namely a lymphocytic interface
dermatitis with a superficially disposed band-like interstitial and perivenular histiocytic infiltrate
obscuring the dermoepidermal junction. The mechanism of granulomatous inflammation in patients with CD
may relate to a dominant T-helper type 1 (Th1)-dominant cytokine milieu.
Th-1 products include interferon (IFN)-g, a potent histiocyte chemotaxin and activator. 
7: Psoriasis-like lesions - in vulva and groin comprising a psoriasiform
diathesis with psoriasiform hyperplasia, spongiform pustulation, granular cell layer diminution and
neutrophil-imbued parakeratosis without attenuation of the suprapapillary plates. There is an
association of psoriasis with CD, both of which appear to be Th1 mediated autoimmune diseases and respond
to recombinant human interleukin-11 therapy.  Common genetic loci implicated in psoriasis and
CD may be important. 
8: Classical metastatic Crohn's disease - characterized by cohesive
epithelioid granulomata involving the entire sampled thickness of the dermis.
9: Other morphological clues to diagnosis - include lymphoplasmacellular or
neutrophilic eccrine hidradenitis and dilated histiocyte-filled lymphatics throughout the dermis. In our
experience, this is seen in some10% of cases of CD but is also seen in skin lesions of rheumatoid
arthritis  and is not pathognomic. The location of such lesions, namely penis, perineum and
perianal skin, implies that perturbed lymphatic drainage reflects peri-rectal disease.
The spectrum of cutaneous lesions in CD is wide. Vasculitis, extravascular neutrophilia and
granulomatous inflammation, typically in concert, are common. Although a similar inflammatory milieu is
seen in the enteric biopsies of these patients, different mechanisms are likely operative in lesional
propagation at skin and intestinal sites.
- Greenstein AJ, Janowitz HD, Sachar DB. The extra-intestinal complications of Crohn's disease and ulcerative colitis: a study of 700 patients. Medicine (Baltimore). 1976;55(5):401-412.
- Magro CM, Crowson AN, Mihm MC. Cutaneous manifestations of gastrointestinal disease : In : Elder DE, Johnson BE, Elenitsas R, Johnson BE, Murphy GF Eds. Lever's Histopathology of the Skin. 9th Ed'n. Philadelphia :JB Lippincott Co. 2004 (in press).
- Crowson AN, Magro CM, Nuovo GJ, Mihm MC Jr. The cutaneous manifestations of Crohn's disease: a study of 32 cases with investigation of the role of the common bacterial sequence 16srDNA in lesional propagation. Hum Pathol (in press).
- Crowson AN, Magro CM, Mihm MC Jr. Pyoderma gangrenosum : A review. J Cutan Pathol 2003;30:97-107.
- Delaney TA, Clay CD, Randell PL. The bowel-associated dermatosis-arthritis syndrome. Australas J Dermatol 1989;30:23-27.
- Smoller BR, Weishar M, Gray MH. An unusual cutaneous manifestation of Crohn's disease. Arch Pathol Lab Med 1990;114:609-610.
- McHenry PM, Hudson M, Smart LM, Rennie JA, Mowat NA, White MI. Pyoderma faciale in a patient with Crohn's disease. Clin Exp Dermatol 1992;17:460-462.
- Magro CM, Crowson AN. Sterile neutrophilic folliculitis with perifollicular vasculopathy: a distinctive cutaneous reaction pattern reflecting systemic disease. J Cutan Pathol. 1998 Apr;25(4):215-21.
- Mitchell IC, Turk JL. An experimental animal model of granulomatous bowel disease. Gut 1989;30:1371-1378.
- Hermon-Taylor J, Bull TJ Sheridan JM, Cheng J, Stellakis ML, Sumar N. Causation of Crohn's disease by Mycobacterium avium subspecies paratuberculosis. Can J Gastroenterol 2000;14:521-539.
- Bernstein CN, Blanchard JF. Viruses and inflammatory bowel disease: is there evidence for a causal association? Inflamm Bowel Dis 2000;6:34-39.
- Kawashima H, Mori T, Kashiwagi Y, Takekuma K, Hoshika A, Wakefield A. Detection and sequencing of measles virus from peripheral mononuclear cells from patients with inflammatory bowel disease and autism. Dig Dis Sci 2000;45:723-729.
- Tiveljung et al, J Med Micro 1999, 48: 263-8Presence of eubacteria in biopsies from Crohn's disease inflammatory lesions as determined by 16S rRNA gene-based PCR. J Med Microbiol. 1999 Mar;48(3):263-8.
- Main J, McKenzie H, Yeaman GR et al. Antibody to Saccharomyces cerevisiae (Baker's yeast) in Crohn's disease. BMJ 1988;297:1105-1106.
- Sanders S, Tahan SR, Kwan T, Magro CM. Giant cells in pyoderma gangrenosum. J Cutan Pathol 2001;28:97-100.
- Magro CM, Crowson AN. Lichenoid and granulomatous dermatitis: a novel cutaneous reaction pattern. Int J Dermatol 2000;39:126-133.
- Romagnani P, Annunziato F, Baccari MC, Parronchi P. T cells and cytokines in Crohn's disease. Curr Opin Immunol 1997;9:793-799.
- Kakazu T, Hara J, Matsumoto T et al. Type 1 T-helper cell predominance in granulomas of Crohn's disease. Am J Gastroenterol 1999;94:2149-2155.
- Sands BE, Bank S, Sninsky CA et al. Preliminary evaluation of safety and activity of recombinant human interleukin 11 in patients with Crohn's disease. Gatroenterol 1999;117:58-61.
- Hussein A. [HLA-27 associated spondyloarthritis in childhood]. Monatsschr Kinderheilkd 1987;135:185-194.
- Magro CM, Crowson AN. The spectrum of cutaneous lesions in rheumatoid arthritis: a clinical and pathological study of 43 patients. J Cutan Pathol 2003;30:1-10.