Zinc deficiency may be secondary to malabsorption or to parenteral nutrition without zinc [6]. Typical features of deficiency include:

Pellagra caused by niacin deficiency has been reported in Crohn disease. Pellagra is characterized by a symmetrical dermatitis on light-exposed skin (the only sign in one third of patients), diarrhea and dementia. A shiny edematous erythema develops on the exposed skin of nose and cheekbones (malar erythema), anterior neck (Casal necklace), and dorsa of the hands. The rash may blister and the skin becomes scalier with time. Heat, friction or pressure triggers the rash. The acute erythema and superficial scaling fade to leave reddish-brown pigmentation. Typically the lips are dry and cracked, the tongue swollen, and the buccal mucosa dry and smooth.

Cutaneous, orofacial, and metastatic Crohn disease are rare. They usually present after the onset of intestinal Crohn disease, but may precede the onset of intestinal disease by months to years. Mean age at presentation is 34 years and cutaneous disease is more common in woman [7, 8].

The pathogenesis of Crohn disease is discussed in the epidemiology and immunobiology chapters of this book.

The morphology of cutaneous Crohn disease is variable. Patients may have a single lesion or widespread disease, but perianal disease is often an early feature. Signs such as perianal erythema, polypoid tags, moist vegetating plaques, perianal fissures, and sinus tracts occur in around one-third of patients. Aphthous ulcers may involve the anal canal and anal sphincter. Severe disease is associated with abscesses and fistulae that may result in scarring with deformity. Crohn disease may also involve surgical sites including laparotomy scars.

Metastatic Crohn disease affects the genitalia, lower extremities, and flexures. Patients present with dusky erythematous papules, plaques, nodules, or ulcers exuding pus. Genitalia may be erythematous, swollen, and indurated, particularly in children.

Orofacial involvement causes persistent lip or cheek swelling with angular cheilitis, indurated fissuring of the lower lip and gingival erythematous papules. The edematous infiltrated buccal mucosa develops a “cobblestone”—like appearance. Aphthous ulcers are common [7, 8].

The differential diagnosis in cutaneous or metastatic Crohn disease is broad and includes granulomatous infections (mycobacterial, spirochetal, deep fungal), foreign body reactions and cutaneous sarcoidosis. Genital or inguinal disease may simulate hidradenitis suppurativa (Fig. 54.1), but the grouped open comedones (blackheads) that are a feature of hidradenitis are not present in Crohn disease. Genital swelling may be caused by obstructive lymphedema. Ulcers in Crohn disease may resemble pyoderma gangrenosum.

Orofacial Crohn disease simulates granulomatous cheilitis (orofacial granulomatosis), a poorly understood condition that causes persistent non-tender swelling of the lips. Rarely these patients develop facial nerve palsy and a fissured tongue (Melkersson–Rosenthal syndrome). In some of these patients lip swelling is triggered by an allergic reaction to foods, food additives, or flavorings such as cinnamates, but this is not common.

Skin biopsy reveals superficial and deep non-caseating granulomas that may be difficult to differentiate from cutaneous sarcoidosis, but the presence of a lymphocyte-rich infiltrate, ulceration and edema favor Crohn disease [7]. Tissue should be cultured to exclude infection.

Chest radiology should be performed to exclude sarcoidosis and patch testing considered in patients with lip swelling .

Treatment is difficult and the course tends to be chronic. Medical options include oral metronidazole (250 mg ×3/day), corticosteroids (very potent topical, intralesional or systemic), sulfasalazine, dapsone, azathioprine and TNF-alpha inhibitors (infliximab, adaluminab) [8].

Low dose antibiotics (e.g., penicillin V 250 mg ×2/day for 6 months) may have a role in patients with persistent lip swelling and fissuring to prevent streptococcal infection and lymphatic damage.

Erythema nodosum is a septal panniculitis most commonly affecting the shins.

Erythema nodosum is the commonest form of panniculitis. It presents most often in Northern European women. Most cases appear between the second and fourth decades, with a peak incidence between the ages of 20 and 30 years. In the Northern hemisphere the incidence peaks in late winter and early spring suggesting an environmental trigger, perhaps streptococcal infection [10].

Erythema nodosum is common in IBD; studies suggest it is present in up to 15 % of patients with Crohn disease and 10 % of patients with ulcerative colitis. The presence of erythema nodosum may correlate with underlying disease activity. Sarcoidosis is one of the commonest causes in the Western world [11]. Erythema nodosum usually occurs in the acute phase in association with bilateral hilar lymphadenopathy [10]. A strong relationship exists to upper respiratory infections with Group A hemolytic streptococcus—the nodules develop 2–3 weeks after the infection. Tuberculosis (now an uncommon cause in Europe), atypical mycobacterial infections, HIV and hepatitis are among other infectious triggers [11, 12]. Numerous medications have been implicated including the oral contraceptive pill, bromides, sulfonamides, penicillin, granulocyte colony stimulating factor, codeine [11] and BRAF inhibitors [13]. Other associations include celiac disease, rheumatoid arthritis, Behçet’s disease and Still’s disease. Erythema nodosum has also been reported in association with malignancies, both hematological and solid organ [13].

No underlying cause is found in 40–60 % of patients [11].

Despite the numerous well-defined provocations, the pathogenesis of erythema nodosum is unclear. The disease may be a hypersensitivity response involving deposition of immune complexes around venues in subcutaneous fat or a type IV delayed hypersensitivity reaction [11].

Patients develop tender, erythematous, warm nodules, measuring 1–5 cm or more in diameter in a symmetrical distribution on the shins, ankles, and knees (Fig. 54.3). Less frequently, nodules appear on the arms or trunk. Fever, malaise, and headache are common. Some patients complain of abdominal pain, vomiting, or diarrhea.

Nodules do not ulcerate, but fade over 2–6 weeks without loss of fat or scarring, leaving a bruise-like discoloration that resolves more slowly. Resolution is usually more rapid in children .

A chronic migratory variant (subacute nodular migratory panniculitis, erythema nodosum migrans) is much less common; the indurated erythematous plaques are tender and may be asymmetrical.

Investigations should ensure there is no other underlying cause in patients with IBD. FBC, ESR, urinalysis and chest radiography should always be performed, but further investigations should be guided by the clinical history and examination. Local prevalence of etiological factors such as bacterial, viral, fungal or protozoal infections should be considered and investigation directed accordingly.

A deep elliptical biopsy including fat is required to demonstrate the typical changes, but is rarely necessary. Histopathology reveals a septal panniculitis, generally with a superficial and deep perivascular lymphocytic infiltrate in the overlying dermis, but no vasculitis [11].

Differential diagnosis includes trauma, cellulitis, insect bites and superficial thrombophlebitis. Nodular vasculitis is another panniculitis, sometimes associated with tuberculosis, that causes symmetrical nodules on the legs; however these nodules tend to be present on the calves rather than the shins and the nodules ulcerate and heal with a depressed scar caused by loss of fat. Histopathology reveals a lobular panniculitis with vasculitis and fat necrosis in contrast to erythema nodosum [12].

Most cases resolve spontaneously within 6 weeks. Relapses are more common in patients with idiopathic disease or in those with preceding upper respiratory tract infection than in patients with an underlying problem such as IBD [11].

Pain should be managed with regular non-steroidal anti-inflammatory drugs. Elevation of the legs and support stockings may help to control swelling and speed resolution. Generally oral corticosteroids are not required. Potassium iodide 200–600 mg/day has been recommended in persistent disease, however this is contraindicated in pregnancy, and has been associated with hypothyroidism [11]. Oral tetracylines have been reported to be of benefit in recalcitrant disease [14, 15].

Pyoderma gangrenosum is an uncommon neutrophilic dermatosis characterized by rapidly enlarging ulcers that are usually extremely painful. The condition was described in 1916 by Broq, and further characterized by Brunstung, Goeckerman, and O’Leary in 1930, who coined the term pyoderma gangrenosum.

The annual incidence of pyoderma gangrenosum is estimated at 3–10 patients per million. Pyoderma gangrenosum is most common in middle-aged adults and has an equal sex distribution; however, it has been described in children and in the elderly. Fifty percent of patients with pyoderma gangrenosum have an associated systemic condition and in approximately one-third this is IBD, more often ulcerative colitis than Crohn disease. Other associations include rheumatoid arthritis, seronegative arthritis, and hematological malignancy (particularly myeloid leukemia). Twenty percent of patients have a monoclonal gammopathy of uncertain significance, most commonly an IgA gammopathy [16, 17].

The etiology and pathogenesis of pyoderma gangrenosum are not well understood, but may be linked to abnormalities in neutrophil function. IgA gammopathies that impair neutrophil function in vitro are associated with pyoderma gangrenosum. Interleukin-8 (IL-8), a leukocyte chemotactant, is overexpressed in pyoderma gangrenosum and ulceration can be induced in xenografts transfected with recombinant human IL-8 [17]. Another clue to the role of neutrophil dysfunction is provided by the dominantly inherited autoinflammatory disorder, PAPA (pyogenic sterile arthritis, pyoderma gangrenosum, and acne). PAPA is caused by mutations in a gene that encodes proline serine threonine phosphatase-interacting protein 1 (PSTPIP-1). PSTPIP-1 co-localizes with pyrin in neutrophils. Normally pyrin downregulates inflammation, but in PAPA, the altered PSTPIP-1 binds more avidly than normal to pyrin, inhibiting its action and leading to activation of IL-1beta and the accumulation of neutrophils [18].

Pathergy (minor trauma triggers ulceration) may play a role in pathogenesis.

A number of variants have been described—see Table 54.4. The classical and pustular forms of pyoderma gangrenosum are those most often associated with IBD [17].

Classical pyoderma gangrenosum is characterized by a painful ulcer with an irregular, undermined violaceous (bluish-red) border and a necrotic base producing a purulent or hemorrhagic exudate (Fig. 54.4). Patients may have a fever and considerable pain. Typically the ulcers enlarge rapidly. The border may become serpiginous if ulceration extends at different rates in different directions. Healing occurs from the edge resulting in a characteristic pattern of scarring with perforations known as “cribriform” (sieve-like) scarring. Pyoderma gangrenosum triggers neither lymphadenopathy nor lymphangitis, despite the inflammatory appearance. Approximately 20 % of patients demonstrate pathergy (new lesions are initiated by minimal trauma). Pyoderma gangrenosum is most common on the lower limbs, the trunk is affected in 10 % of patients and lesions on the head, groin, genitalia or upper extremities are less common. A sterile neutrophilic infiltrate may be found in other organs, e.g., lungs, heart, liver, spleen, gastrointestinal tract, and lymph nodes.

Rarely pyoderma gangrenosum develops around the stoma of patients with IBD (Fig. 54.5). Peri-stomal pyoderma gangrenosum may present from a few months to many years after the formation of the stoma. Pathergy may play a role in pathogenesis of peri-stomal PG skin may be irritated by leakage of stomal contents or by adhesives used to attach the stoma bag.