Cutis

Dermatitis herpetiformis (DH) is a chronic pruritic cutaneous eruption associated with gluten-sensitive enteropathy (celiac disease [CD]) and immunoglobulin A (IgA) deposition in the skin. While the disease is not uncommon among adolescents, DH is rarely seen in prepubertal patients. Children with DH present similarly to adults; however, uncommon skin findings have been reported. Because of an increased risk for autoimmune diseases and lymphoma, accurate diagnosis and treatment are imperative. We present a case of DH in a 6-year-old Latino boy previously diagnosed with atopic dermatitis and recurrent urticaria. Our aim is to highlight the various cutaneous presentations of DH and encourage clinicians to consider this diagnosis in young patients with recalcitrant atypical skin disease.
Case Report
A 6-year-old Latino boy presented with a history of pruritic skin lesions (beginning at the age of 9 months) previously diagnosed as atopic dermatitis and recurrent urticaria. His pediatrician prescribed topical steroids and oral diphenhydramine hydrochloride, without improvement. On examination, the patient had few excoriated edematous papules on his buttocks (Figure 1) and urticarial plaques on his upper extremity. His skin was xerotic but lacked any lichenified plaques or papules in the antecubital and popliteal fossae. The patient denied any associated nausea or diarrhea. Family history was negative for atopy and autoimmune disease. The mother reported that the patient was, at one time, "small for his age" but is now closer in size to his peers.

A punch biopsy was obtained from an urticarial plaque on his arm and treatment was initiated with desonide cream 0.05% twice daily to the affected areas. The biopsy revealed collections of neutrophils in the papillary dermis as well as clefting at the dermoepidermal junction (Figure 2). A second biopsy for direct immunofluorescence (DIF) was performed from perilesional gluteal skin. This specimen exhibited granular immunoglobulin A (IgA) deposits in the papillary dermis, thus confirming the diagnosis of dermatitis herpetiformis (DH).

Evaluation by a gastroenterologist who performed serologic testing and endoscopic biopsy of the small intestine further substantiated the diagnosis. In the serum, the presence of immunoglobulin G antigliadin (42.3 U/mL; reference, 100 U/mL; reference, <10), IgA anti–tissue transglutaminase (anti-tTGase)(>100 U/mL; reference, <4), and IgA antiendomysial (positive; reference, negative) antibodies were detected. The intestinal biopsy revealed villous atrophy accompanied by duodenitis consistent with celiac disease (CD). HLA typing was not performed. A complete blood count with differential blood count, comprehensive metabolic panel, thyroxine, thyroid stimulating hormone, and thyroglobulin antibodies were all within reference range. The patient was initiated on a gluten-free diet and subsequently developed fewer lesions and reduced pruritus.

Comment

DH is a cutaneous manifestation of CD, which is an immune-mediated enteropathy caused by gluten sensitivity. The symptoms of childhood CD include persistent diarrhea, failure to thrive, abdominal pain, and vomiting. Iron deficiency anemia also may be present as well as other sequelae of malabsorption. Although patients with DH usually do not have gastrointestinal symptoms, virtually all patients with DH show evidence of the same gluten-sensitive enteropathy of the small bowel.
Gluten is a grain protein found in wheat, barley, and rye, but not in oats. Gliadin, the alcohol-soluble fraction of gluten, is believed to be the inciting stimulus.1 In addition to antigliadin antibodies, patients with DH have circulating antiendomysial and antitransglutaminase antibodies with uncertain roles in pathogenesis. The prevailing theory suggests that gluten sensitivity leads to the formation of IgA antibodies to gluten-transglutaminase complexes. These antibodies cross-react with other transglutaminases, specifically epidermal transglutaminase, which is highly homologous. Deposition of IgA–transglutaminase 3 complexes within the papillary dermis cause skin lesions of DH.2,3
Childhood DH is rare, with an uncertain incidence and prevalence. Cases have been reported in children as young as 8 months,4 but most children receive the diagnosis between the ages of 2 and 7 years.5 DH is most prevalent in individuals of Northern European descent. In adults, men with DH outnumber women by a ratio of nearly 2:16; however, among childhood cases, there is a female predominance.5,7 A genetic predisposition for gluten sensitivity is supported by the high prevalence of DH and CD among first-degree relatives of known patients with DH and CD as well as a documented HLA association. The DQ2 and DQ8 alleles are most closely linked with DH and CD.8
The clinical presentation of DH is characterized by symmetrically distributed papulovesicular lesions and urticarial plaques, often favoring the back, buttocks, and extensor surfaces of the extremities. Because the lesions are intensely pruritic, intact vesicles are rarely observed by the clinician. Children, by most accounts, present similarly to adults; however, uncommon skin findings may be present and include isolated involvement of the palms,9 hemorrhagic lesions of the palms and soles,10 deep dermal papules and nodules,11 and facial lesions.5,11 Powell et al12 described a case with a predominance of urticarial lesions. Thus, childhood DH often is misdiagnosed as atopic dermatitis, papular urticaria, scabies, linear IgA dermatosis, or chronic urticaria. Recalcitrant cases of these diseases or patients who present with atypical findings of common diseases like atopic dermatitis should prompt the clinician to consider DH in the differential diagnosis.
The gold standard for diagnosing DH is DIF of a biopsy from perilesional skin, which shows granular IgA deposits most often localized to the papillary dermis. For routine histology, a biopsy of an intact vesicle is preferred where neutrophils in the papillary dermis and clefting at the dermoepidermal junction are seen. Although granular IgA deposits seen on DIF are highly specific for DH, up to 10% of cases may have a negative DIF.13,14 To confirm the diagnosis, serologic testing for anti-tTGase antibodies is useful. Using an enzyme-linked immunosorbent assay, tTGase antibodies can be detected in serum with specificity and sensitivity above 90% for patients on normal diets.15,16 Desai et al17 documented the cost-effectiveness of enzyme-linked immunosorbent assay tTGase testing and proposed that serologic testing be used primarily in the diagnosis of DH. Once patients remove gluten from their diet, the skin lesions and enteropathy resolve. Furthermore, tTGase antibodies decrease to levels within reference range in the absence of gluten; thus, serologic testing can be used to monitor dietary compliance.
Patients with DH are at higher risk for autoimmune diseases, particularly Hashimoto thyroiditis, pernicious anemia, and type 1 diabetes mellitus, among others.18-20 The association between DH and lymphoma, mostly T-cell lymphoma, is well-documented, with 78% of lymphomas arising from the small bowel, thus warranting vigilant surveillance and regular follow-up with a gastroenterologist.21 Lewis et al,22 in a retrospective study of 487 patients with DH, found that lymphoma only occurred in patients not on gluten-free diets or in patients who had followed the gluten-free diet for less than 5 years. Moreover, patients in this study who did adhere to the gluten-free diet had no increased risk for developing lymphoma over the general population.22
The primary treatment of DH is a gluten-free diet that is protective against the development of lymphoma. Dietary compliance is challenging, especially for children; therefore, referral to a dietician familiar with this area is helpful. Because months of dietary restriction are needed before a response is noted, many patients require pharmacologic treatment with dapsone. The recommended starting dose for children is 2 mg/kg daily with titration based on clinical response.23 Most patients will have a rapid response to dapsone within 48 to 72 hours. However, the enteropathy is unaffected by dapsone therapy and patients should be encouraged to maintain dietary compliance.

Conclusion

Childhood DH is rare and can present with atypical lesions involving the palms and soles, urticarial lesions, deep dermal papules and nodules, and facial lesions. If aware of these unusual presentations, clinicians may consider the diagnosis of DH and act to further evaluate cases of suspected common diseases not responding to treatment.

Dermatitis herpetiformis (DH) is a chronic pruritic cutaneous eruption associated with gluten-sensitive enteropathy (celiac disease [CD]) and immunoglobulin A (IgA) deposition in the skin. While the disease is not uncommon among adolescents, DH is rarely seen in prepubertal patients. Children with DH present similarly to adults; however, uncommon skin findings have been reported. Because of an increased risk for autoimmune diseases and lymphoma, accurate diagnosis and treatment are imperative. We present a case of DH in a 6-year-old Latino boy previously diagnosed with atopic dermatitis and recurrent urticaria. Our aim is to highlight the various cutaneous presentations of DH and encourage clinicians to consider this diagnosis in young patients with recalcitrant atypical skin disease.
Case Report
A 6-year-old Latino boy presented with a history of pruritic skin lesions (beginning at the age of 9 months) previously diagnosed as atopic dermatitis and recurrent urticaria. His pediatrician prescribed topical steroids and oral diphenhydramine hydrochloride, without improvement. On examination, the patient had few excoriated edematous papules on his buttocks (Figure 1) and urticarial plaques on his upper extremity. His skin was xerotic but lacked any lichenified plaques or papules in the antecubital and popliteal fossae. The patient denied any associated nausea or diarrhea. Family history was negative for atopy and autoimmune disease. The mother reported that the patient was, at one time, "small for his age" but is now closer in size to his peers.

A punch biopsy was obtained from an urticarial plaque on his arm and treatment was initiated with desonide cream 0.05% twice daily to the affected areas. The biopsy revealed collections of neutrophils in the papillary dermis as well as clefting at the dermoepidermal junction (Figure 2). A second biopsy for direct immunofluorescence (DIF) was performed from perilesional gluteal skin. This specimen exhibited granular immunoglobulin A (IgA) deposits in the papillary dermis, thus confirming the diagnosis of dermatitis herpetiformis (DH).

Evaluation by a gastroenterologist who performed serologic testing and endoscopic biopsy of the small intestine further substantiated the diagnosis. In the serum, the presence of immunoglobulin G antigliadin (42.3 U/mL; reference, 100 U/mL; reference, <10), IgA anti–tissue transglutaminase (anti-tTGase)(>100 U/mL; reference, <4), and IgA antiendomysial (positive; reference, negative) antibodies were detected. The intestinal biopsy revealed villous atrophy accompanied by duodenitis consistent with celiac disease (CD). HLA typing was not performed. A complete blood count with differential blood count, comprehensive metabolic panel, thyroxine, thyroid stimulating hormone, and thyroglobulin antibodies were all within reference range. The patient was initiated on a gluten-free diet and subsequently developed fewer lesions and reduced pruritus.

Comment

DH is a cutaneous manifestation of CD, which is an immune-mediated enteropathy caused by gluten sensitivity. The symptoms of childhood CD include persistent diarrhea, failure to thrive, abdominal pain, and vomiting. Iron deficiency anemia also may be present as well as other sequelae of malabsorption. Although patients with DH usually do not have gastrointestinal symptoms, virtually all patients with DH show evidence of the same gluten-sensitive enteropathy of the small bowel.
Gluten is a grain protein found in wheat, barley, and rye, but not in oats. Gliadin, the alcohol-soluble fraction of gluten, is believed to be the inciting stimulus.1 In addition to antigliadin antibodies, patients with DH have circulating antiendomysial and antitransglutaminase antibodies with uncertain roles in pathogenesis. The prevailing theory suggests that gluten sensitivity leads to the formation of IgA antibodies to gluten-transglutaminase complexes. These antibodies cross-react with other transglutaminases, specifically epidermal transglutaminase, which is highly homologous. Deposition of IgA–transglutaminase 3 complexes within the papillary dermis cause skin lesions of DH.2,3
Childhood DH is rare, with an uncertain incidence and prevalence. Cases have been reported in children as young as 8 months,4 but most children receive the diagnosis between the ages of 2 and 7 years.5 DH is most prevalent in individuals of Northern European descent. In adults, men with DH outnumber women by a ratio of nearly 2:16; however, among childhood cases, there is a female predominance.5,7 A genetic predisposition for gluten sensitivity is supported by the high prevalence of DH and CD among first-degree relatives of known patients with DH and CD as well as a documented HLA association. The DQ2 and DQ8 alleles are most closely linked with DH and CD.8
The clinical presentation of DH is characterized by symmetrically distributed papulovesicular lesions and urticarial plaques, often favoring the back, buttocks, and extensor surfaces of the extremities. Because the lesions are intensely pruritic, intact vesicles are rarely observed by the clinician. Children, by most accounts, present similarly to adults; however, uncommon skin findings may be present and include isolated involvement of the palms,9 hemorrhagic lesions of the palms and soles,10 deep dermal papules and nodules,11 and facial lesions.5,11 Powell et al12 described a case with a predominance of urticarial lesions. Thus, childhood DH often is misdiagnosed as atopic dermatitis, papular urticaria, scabies, linear IgA dermatosis, or chronic urticaria. Recalcitrant cases of these diseases or patients who present with atypical findings of common diseases like atopic dermatitis should prompt the clinician to consider DH in the differential diagnosis.
The gold standard for diagnosing DH is DIF of a biopsy from perilesional skin, which shows granular IgA deposits most often localized to the papillary dermis. For routine histology, a biopsy of an intact vesicle is preferred where neutrophils in the papillary dermis and clefting at the dermoepidermal junction are seen. Although granular IgA deposits seen on DIF are highly specific for DH, up to 10% of cases may have a negative DIF.13,14 To confirm the diagnosis, serologic testing for anti-tTGase antibodies is useful. Using an enzyme-linked immunosorbent assay, tTGase antibodies can be detected in serum with specificity and sensitivity above 90% for patients on normal diets.15,16 Desai et al17 documented the cost-effectiveness of enzyme-linked immunosorbent assay tTGase testing and proposed that serologic testing be used primarily in the diagnosis of DH. Once patients remove gluten from their diet, the skin lesions and enteropathy resolve. Furthermore, tTGase antibodies decrease to levels within reference range in the absence of gluten; thus, serologic testing can be used to monitor dietary compliance.
Patients with DH are at higher risk for autoimmune diseases, particularly Hashimoto thyroiditis, pernicious anemia, and type 1 diabetes mellitus, among others.18-20 The association between DH and lymphoma, mostly T-cell lymphoma, is well-documented, with 78% of lymphomas arising from the small bowel, thus warranting vigilant surveillance and regular follow-up with a gastroenterologist.21 Lewis et al,22 in a retrospective study of 487 patients with DH, found that lymphoma only occurred in patients not on gluten-free diets or in patients who had followed the gluten-free diet for less than 5 years. Moreover, patients in this study who did adhere to the gluten-free diet had no increased risk for developing lymphoma over the general population.22
The primary treatment of DH is a gluten-free diet that is protective against the development of lymphoma. Dietary compliance is challenging, especially for children; therefore, referral to a dietician familiar with this area is helpful. Because months of dietary restriction are needed before a response is noted, many patients require pharmacologic treatment with dapsone. The recommended starting dose for children is 2 mg/kg daily with titration based on clinical response.23 Most patients will have a rapid response to dapsone within 48 to 72 hours. However, the enteropathy is unaffected by dapsone therapy and patients should be encouraged to maintain dietary compliance.

Conclusion

Childhood DH is rare and can present with atypical lesions involving the palms and soles, urticarial lesions, deep dermal papules and nodules, and facial lesions. If aware of these unusual presentations, clinicians may consider the diagnosis of DH and act to further evaluate cases of suspected common diseases not responding to treatment.

Dermatitis herpetiformis (DH) is a chronic pruritic cutaneous eruption associated with gluten-sensitive enteropathy (celiac disease [CD]) and immunoglobulin A (IgA) deposition in the skin. While the disease is not uncommon among adolescents, DH is rarely seen in prepubertal patients. Children with DH present similarly to adults; however, uncommon skin findings have been reported. Because of an increased risk for autoimmune diseases and lymphoma, accurate diagnosis and treatment are imperative. We present a case of DH in a 6-year-old Latino boy previously diagnosed with atopic dermatitis and recurrent urticaria. Our aim is to highlight the various cutaneous presentations of DH and encourage clinicians to consider this diagnosis in young patients with recalcitrant atypical skin disease.
Case Report
A 6-year-old Latino boy presented with a history of pruritic skin lesions (beginning at the age of 9 months) previously diagnosed as atopic dermatitis and recurrent urticaria. His pediatrician prescribed topical steroids and oral diphenhydramine hydrochloride, without improvement. On examination, the patient had few excoriated edematous papules on his buttocks (Figure 1) and urticarial plaques on his upper extremity. His skin was xerotic but lacked any lichenified plaques or papules in the antecubital and popliteal fossae. The patient denied any associated nausea or diarrhea. Family history was negative for atopy and autoimmune disease. The mother reported that the patient was, at one time, "small for his age" but is now closer in size to his peers.

A punch biopsy was obtained from an urticarial plaque on his arm and treatment was initiated with desonide cream 0.05% twice daily to the affected areas. The biopsy revealed collections of neutrophils in the papillary dermis as well as clefting at the dermoepidermal junction (Figure 2). A second biopsy for direct immunofluorescence (DIF) was performed from perilesional gluteal skin. This specimen exhibited granular immunoglobulin A (IgA) deposits in the papillary dermis, thus confirming the diagnosis of dermatitis herpetiformis (DH).

Evaluation by a gastroenterologist who performed serologic testing and endoscopic biopsy of the small intestine further substantiated the diagnosis. In the serum, the presence of immunoglobulin G antigliadin (42.3 U/mL; reference, 100 U/mL; reference, <10), IgA anti–tissue transglutaminase (anti-tTGase)(>100 U/mL; reference, <4), and IgA antiendomysial (positive; reference, negative) antibodies were detected. The intestinal biopsy revealed villous atrophy accompanied by duodenitis consistent with celiac disease (CD). HLA typing was not performed. A complete blood count with differential blood count, comprehensive metabolic panel, thyroxine, thyroid stimulating hormone, and thyroglobulin antibodies were all within reference range. The patient was initiated on a gluten-free diet and subsequently developed fewer lesions and reduced pruritus.

Comment

DH is a cutaneous manifestation of CD, which is an immune-mediated enteropathy caused by gluten sensitivity. The symptoms of childhood CD include persistent diarrhea, failure to thrive, abdominal pain, and vomiting. Iron deficiency anemia also may be present as well as other sequelae of malabsorption. Although patients with DH usually do not have gastrointestinal symptoms, virtually all patients with DH show evidence of the same gluten-sensitive enteropathy of the small bowel.
Gluten is a grain protein found in wheat, barley, and rye, but not in oats. Gliadin, the alcohol-soluble fraction of gluten, is believed to be the inciting stimulus.1 In addition to antigliadin antibodies, patients with DH have circulating antiendomysial and antitransglutaminase antibodies with uncertain roles in pathogenesis. The prevailing theory suggests that gluten sensitivity leads to the formation of IgA antibodies to gluten-transglutaminase complexes. These antibodies cross-react with other transglutaminases, specifically epidermal transglutaminase, which is highly homologous. Deposition of IgA–transglutaminase 3 complexes within the papillary dermis cause skin lesions of DH.2,3
Childhood DH is rare, with an uncertain incidence and prevalence. Cases have been reported in children as young as 8 months,4 but most children receive the diagnosis between the ages of 2 and 7 years.5 DH is most prevalent in individuals of Northern European descent. In adults, men with DH outnumber women by a ratio of nearly 2:16; however, among childhood cases, there is a female predominance.5,7 A genetic predisposition for gluten sensitivity is supported by the high prevalence of DH and CD among first-degree relatives of known patients with DH and CD as well as a documented HLA association. The DQ2 and DQ8 alleles are most closely linked with DH and CD.8
The clinical presentation of DH is characterized by symmetrically distributed papulovesicular lesions and urticarial plaques, often favoring the back, buttocks, and extensor surfaces of the extremities. Because the lesions are intensely pruritic, intact vesicles are rarely observed by the clinician. Children, by most accounts, present similarly to adults; however, uncommon skin findings may be present and include isolated involvement of the palms,9 hemorrhagic lesions of the palms and soles,10 deep dermal papules and nodules,11 and facial lesions.5,11 Powell et al12 described a case with a predominance of urticarial lesions. Thus, childhood DH often is misdiagnosed as atopic dermatitis, papular urticaria, scabies, linear IgA dermatosis, or chronic urticaria. Recalcitrant cases of these diseases or patients who present with atypical findings of common diseases like atopic dermatitis should prompt the clinician to consider DH in the differential diagnosis.
The gold standard for diagnosing DH is DIF of a biopsy from perilesional skin, which shows granular IgA deposits most often localized to the papillary dermis. For routine histology, a biopsy of an intact vesicle is preferred where neutrophils in the papillary dermis and clefting at the dermoepidermal junction are seen. Although granular IgA deposits seen on DIF are highly specific for DH, up to 10% of cases may have a negative DIF.13,14 To confirm the diagnosis, serologic testing for anti-tTGase antibodies is useful. Using an enzyme-linked immunosorbent assay, tTGase antibodies can be detected in serum with specificity and sensitivity above 90% for patients on normal diets.15,16 Desai et al17 documented the cost-effectiveness of enzyme-linked immunosorbent assay tTGase testing and proposed that serologic testing be used primarily in the diagnosis of DH. Once patients remove gluten from their diet, the skin lesions and enteropathy resolve. Furthermore, tTGase antibodies decrease to levels within reference range in the absence of gluten; thus, serologic testing can be used to monitor dietary compliance.
Patients with DH are at higher risk for autoimmune diseases, particularly Hashimoto thyroiditis, pernicious anemia, and type 1 diabetes mellitus, among others.18-20 The association between DH and lymphoma, mostly T-cell lymphoma, is well-documented, with 78% of lymphomas arising from the small bowel, thus warranting vigilant surveillance and regular follow-up with a gastroenterologist.21 Lewis et al,22 in a retrospective study of 487 patients with DH, found that lymphoma only occurred in patients not on gluten-free diets or in patients who had followed the gluten-free diet for less than 5 years. Moreover, patients in this study who did adhere to the gluten-free diet had no increased risk for developing lymphoma over the general population.22
The primary treatment of DH is a gluten-free diet that is protective against the development of lymphoma. Dietary compliance is challenging, especially for children; therefore, referral to a dietician familiar with this area is helpful. Because months of dietary restriction are needed before a response is noted, many patients require pharmacologic treatment with dapsone. The recommended starting dose for children is 2 mg/kg daily with titration based on clinical response.23 Most patients will have a rapid response to dapsone within 48 to 72 hours. However, the enteropathy is unaffected by dapsone therapy and patients should be encouraged to maintain dietary compliance.

Conclusion

Childhood DH is rare and can present with atypical lesions involving the palms and soles, urticarial lesions, deep dermal papules and nodules, and facial lesions. If aware of these unusual presentations, clinicians may consider the diagnosis of DH and act to further evaluate cases of suspected common diseases not responding to treatment.

A metastatic malignancy of the umbilicus is commonly termed Sister Mary Joseph nodule (SMJN). It is a rare occurrence but may represent the first sign of a visceral malignancy and therefore should prompt a thorough search for the primary tumor. Typically, the most common origin of an umbilical metastasis is an adenocarcinoma from a gastrointestinal or gynecologic primary malignancy. The presence of SMJN carries a poor prognosis with the average survival time at the appearance of an umbilical metastasis being 10 months. We report a case of a 66-year-old man who was referred for evaluation of an enlarging umbilical lesion. Histopathology revealed adenocarcinoma. After a full metastatic workup, the tumor of origin was identified as adenocarcinoma of the sigmoid colon. Benign tumors of the umbilicus are uncommon. This case report serves to emphasize the importance of obtaining a histologic diagnosis when any new lesion presents in the umbilical region.

Case Report
A 66-year-old white man presented for evaluation of an umbilical lesion of 3 weeks' duration. The lesion was asymptomatic and nontender but was bleeding and oozing. The lesion, diagnosed by the patient's primary care physician as an infected pyogenic granuloma, was treated with oral antibiotics, without relief. His past medical history was unremarkable. He took no medications at that time and had an allergy to quinolones. His dermatologic history was positive for numerous actinic keratoses and a basal cell carcinoma on the forehead. Physical examination upon presentation revealed a 3-cm fungating polypoid umbilical mass with copious purulent exudates similar to Figure 1.1 The clinical differential diagnosis at that time included a pyogenic granuloma versus a Sister Mary Joseph nodule (SMJN). A shave biopsy was performed. Histopathology revealed multiple cystic and ductal spaces lined by atypical epithelial cells with numerous mitotic figures in the dermis (Figures 2 and 3). These changes favored a gastrointestinal primary lesion, supporting the clinical diagnosis of SMJN. The patient subsequently underwent a full metastatic workup. A computed tomographic scan of the abdomen and pelvis demonstrated no definite metastases to the lungs or liver but suggested a near-obstructing distal bowel primary tumor. A colonoscopy demonstrated a near-obstructing sigmoid colon carcinoma. The patient subsequently underwent an exploratory laparotomy, sigmoid resection, and primary colonic reanastomosis. Liver biopsies and resection of the omentum and the periumbilical abdominal wall including the eroding metastasis were performed as well as multiple peritoneal biopsies. Pathologic evaluation confirmed the presence of extensive carcinomatosis. The primary tumor was a 5.0X3.0-cm moderately differentiated adenocarcinoma of the sigmoid colon with extension through the bowel wall. Biopsies of the liver, lymph nodes, periumbilical soft tissue, omentum, and peritoneum were all positive for metastatic carcinoma. Postoperatively, the patient was started on the FOLFOX regimen incorporating folinic acid, 5-fluorouracil, and oxaliplatin. Currently, the patient remains clinically stable and without evidence of progressive sigmoid colon carcinoma.

Comment
SMJN is the term applied to an uncommon metastatic malignancy of the umbilicus. This eponym, coined by Sir Hamilton Bailey in his book Physical Signs in Clinical Surgery,2 honors Sister Mary Joseph Dempsey, a nun in the Franciscan order who was the first surgical assistant to Dr. William J. Mayo at St. Mary's Hospital in Rochester, Minnesota.3,4 Sister Mary Joseph made the astute observation that patients with gastrointestinal and gynecologic tumors may have involvement of the umbilicus; if there is involvement of the umbilicus, the prognosis is poor.5 Although Dr. Mayo gives credit to Sister Mary Joseph, contrary to what some believe, he is not responsible for the eponym. Dr. Mayo used the term pants button umbilicus in his article; Sir Bailey definitively coined the term SMJN. Some authors argue that the correct name is Sister Joseph's nodule; however, SMJN remains the more commonly used term.6 Frequency—Cutaneous metastasis, in and of itself, is a rare feature of visceral malignancy, occurring in about 1% to 2% of cases, with umbilical metastasis occurring even less frequently. There are approximately 265 cases of SMJN reported in the literature up to 1990, emphasizing its infrequency. The most common origin of an umbilical metastasis is an adenocarcinoma from a gastrointestinal or gynecologic primary malignancy. In a review of the world literature on metastatic umbilical tumors, Barrow7 found that the most common primary tumor identified was carcinoma of the stomach. The second most common was ovarian tumor,7 with colon, rectal, and pancreatic cancers following in descending order of frequency.8 In very rare cases, the primary tumor involved the breast, cervix, endometrium, small bowel, liver, gallbladder, lung, prostate, kidney, fallopian tube, appendix, and penis.9 In approximately 20% to 30% of cases, the primary tumor could not be identified.9 Umbilical Anatomy—A neoplasm may metastasize to the umbilicus by one of many mechanisms, most commonly direct extension from the anterior peritoneal surface from adjacent organs. Other mechanisms of metastasis include vascular spread via arterial and venous channels, lymphatic spread, and umbilical ligamentous spread. The rich vascular supply to the anterior abdominal wall facilitates metastasis of a neoplasm. The main arteries supplying the umbilical region are the inferior epigastric, deep circumflex iliac, and superior epigastric arteries. Venous drainage of the umbilical region stems from a network of veins radiating from the umbilicus, including the axillary vein above and the femoral vein below the umbilicus. There also are small paraumbilical veins that connect with the portal system along the ligamentum teres hepatis, the superior portion of the falciform ligament.10 The superficial lymphatic drainage of the periumbilical region leads to axillary lymph nodes above and inguinal lymph nodes below the periumbilical region. The deep lymphatic drainage runs along the falciform ligament of the liver and then enters the anterior mediastinum by traversing the diaphragm. Inferiorly, the deep lymphatics communicate by coursing to the lymph nodes of the iliac arteries. Because the lymphatic channels of the periumbilical region communicate with the deep inguinal, axillary, deep femoral, and periaortic lymph nodes, once a neoplasm is established at the umbilicus, it can metastasize to any part of the body,8 supporting the notion that the presence of SMJN portends a poor prognosis. In the fetus, the umbilicus serves as the opening for the umbilical vessels. In the adult, there are several ligaments that contain remnants of obliterated fetal structures and connect to the umbilicus. For example, the median umbilical ligament, also known as the urachus, represents the obliterated umbilical arteries that formerly connected the umbilicus to the bladder. The falciform ligament in the adult contains the obliterated umbilical vein and runs along the hepatic surface. Therefore, a firm command of the anatomy and embryology of the periumbilical region is essential for an accurate clinical workup once the diagnosis of SMJN has been established. Physical Examination—Clinically, SMJN usually presents as a firm indurated plaque or nodule that is 0.5 to 2 cm in size, though lesions up to 10 cm have been reported. The lesion is occasionally painful and may have a fibrous consistency with irregular edges that are attached to the anterior abdominal wall. It tends to have a vascular appearance and can be fissured, ulcerated, or necrotic. Purulent discharge may be present if it is secondarily infected. Typically, there are no gross features to distinguish between a primary and secondary umbilical tumor. Differential Diagnosis—The differential diagnosis of SMJN includes a primary carcinoma of the umbilicus, a benign umbilical lesion, and a metastatic lesion of the umbilicus. Primary umbilical carcinomas are rare and include malignant melanoma, basal cell carcinoma, and omphalomesenteric duct carcinoma. Endometriosis is the most common benign lesion of the umbilicus. Other benign umbilical lesions include papillomas, epidermal/inclusion cysts, seborrheic keratoses, dermal nevi, polyps, congenital malformations, foreign bodies, talc granulomas, angiomas, pyogenic and pilonidal granulomas, keloids, incarcerated hernias, angiokeratomas, and lymphangiomas.11 Histopathology—In general, the histology of a cutaneous metastatic lesion is of finite value in determining the site of the primary malignancy. In contrast, when speaking of an umbilical metastasis, histologic sampling more often aids in determining the derivation.11 The histopathology is dependent on the primary tumor and is most often adenocarcinoma, which was the case with our patient. Prognosis—Although the presence of umbilical disease indicates metastasis, it does not suggest unresectability and, in fact, may be the first sign of a recurrence.11 However, in general, SMJN portends a poor prognosis and is considered an ominous sign. The presence of SMJN should prompt a thorough metastatic workup and appropriate clinical staging. Survival time in untreated patients ranges from 2 to 11 months, with 10 months as the average survival time from the appearance of an umbilical metastasis.6,9 This rapid deterioration may be, in part, caused by the rich lymphatic network in the abdominal wall providing communication with the deep inguinal, axillary, deep femoral, and periaortic lymph nodes. Therefore, from the umbilicus, a tumor may spread to many parts of the body.

Conclusion
Cutaneous metastasis is a rare occurrence, making SMJN exceptionally infrequent. The finding of SMJN should prompt a thorough search for the primary malignancy. As demonstrated by our patient, SMJN may be the first sign of a visceral malignancy, making proper and timely diagnosis lifesaving.

A metastatic malignancy of the umbilicus is commonly termed Sister Mary Joseph nodule (SMJN). It is a rare occurrence but may represent the first sign of a visceral malignancy and therefore should prompt a thorough search for the primary tumor. Typically, the most common origin of an umbilical metastasis is an adenocarcinoma from a gastrointestinal or gynecologic primary malignancy. The presence of SMJN carries a poor prognosis with the average survival time at the appearance of an umbilical metastasis being 10 months. We report a case of a 66-year-old man who was referred for evaluation of an enlarging umbilical lesion. Histopathology revealed adenocarcinoma. After a full metastatic workup, the tumor of origin was identified as adenocarcinoma of the sigmoid colon. Benign tumors of the umbilicus are uncommon. This case report serves to emphasize the importance of obtaining a histologic diagnosis when any new lesion presents in the umbilical region.

Case Report
A 66-year-old white man presented for evaluation of an umbilical lesion of 3 weeks' duration. The lesion was asymptomatic and nontender but was bleeding and oozing. The lesion, diagnosed by the patient's primary care physician as an infected pyogenic granuloma, was treated with oral antibiotics, without relief. His past medical history was unremarkable. He took no medications at that time and had an allergy to quinolones. His dermatologic history was positive for numerous actinic keratoses and a basal cell carcinoma on the forehead. Physical examination upon presentation revealed a 3-cm fungating polypoid umbilical mass with copious purulent exudates similar to Figure 1.1 The clinical differential diagnosis at that time included a pyogenic granuloma versus a Sister Mary Joseph nodule (SMJN). A shave biopsy was performed. Histopathology revealed multiple cystic and ductal spaces lined by atypical epithelial cells with numerous mitotic figures in the dermis (Figures 2 and 3). These changes favored a gastrointestinal primary lesion, supporting the clinical diagnosis of SMJN. The patient subsequently underwent a full metastatic workup. A computed tomographic scan of the abdomen and pelvis demonstrated no definite metastases to the lungs or liver but suggested a near-obstructing distal bowel primary tumor. A colonoscopy demonstrated a near-obstructing sigmoid colon carcinoma. The patient subsequently underwent an exploratory laparotomy, sigmoid resection, and primary colonic reanastomosis. Liver biopsies and resection of the omentum and the periumbilical abdominal wall including the eroding metastasis were performed as well as multiple peritoneal biopsies. Pathologic evaluation confirmed the presence of extensive carcinomatosis. The primary tumor was a 5.0X3.0-cm moderately differentiated adenocarcinoma of the sigmoid colon with extension through the bowel wall. Biopsies of the liver, lymph nodes, periumbilical soft tissue, omentum, and peritoneum were all positive for metastatic carcinoma. Postoperatively, the patient was started on the FOLFOX regimen incorporating folinic acid, 5-fluorouracil, and oxaliplatin. Currently, the patient remains clinically stable and without evidence of progressive sigmoid colon carcinoma.

Comment
SMJN is the term applied to an uncommon metastatic malignancy of the umbilicus. This eponym, coined by Sir Hamilton Bailey in his book Physical Signs in Clinical Surgery,2 honors Sister Mary Joseph Dempsey, a nun in the Franciscan order who was the first surgical assistant to Dr. William J. Mayo at St. Mary's Hospital in Rochester, Minnesota.3,4 Sister Mary Joseph made the astute observation that patients with gastrointestinal and gynecologic tumors may have involvement of the umbilicus; if there is involvement of the umbilicus, the prognosis is poor.5 Although Dr. Mayo gives credit to Sister Mary Joseph, contrary to what some believe, he is not responsible for the eponym. Dr. Mayo used the term pants button umbilicus in his article; Sir Bailey definitively coined the term SMJN. Some authors argue that the correct name is Sister Joseph's nodule; however, SMJN remains the more commonly used term.6 Frequency—Cutaneous metastasis, in and of itself, is a rare feature of visceral malignancy, occurring in about 1% to 2% of cases, with umbilical metastasis occurring even less frequently. There are approximately 265 cases of SMJN reported in the literature up to 1990, emphasizing its infrequency. The most common origin of an umbilical metastasis is an adenocarcinoma from a gastrointestinal or gynecologic primary malignancy. In a review of the world literature on metastatic umbilical tumors, Barrow7 found that the most common primary tumor identified was carcinoma of the stomach. The second most common was ovarian tumor,7 with colon, rectal, and pancreatic cancers following in descending order of frequency.8 In very rare cases, the primary tumor involved the breast, cervix, endometrium, small bowel, liver, gallbladder, lung, prostate, kidney, fallopian tube, appendix, and penis.9 In approximately 20% to 30% of cases, the primary tumor could not be identified.9 Umbilical Anatomy—A neoplasm may metastasize to the umbilicus by one of many mechanisms, most commonly direct extension from the anterior peritoneal surface from adjacent organs. Other mechanisms of metastasis include vascular spread via arterial and venous channels, lymphatic spread, and umbilical ligamentous spread. The rich vascular supply to the anterior abdominal wall facilitates metastasis of a neoplasm. The main arteries supplying the umbilical region are the inferior epigastric, deep circumflex iliac, and superior epigastric arteries. Venous drainage of the umbilical region stems from a network of veins radiating from the umbilicus, including the axillary vein above and the femoral vein below the umbilicus. There also are small paraumbilical veins that connect with the portal system along the ligamentum teres hepatis, the superior portion of the falciform ligament.10 The superficial lymphatic drainage of the periumbilical region leads to axillary lymph nodes above and inguinal lymph nodes below the periumbilical region. The deep lymphatic drainage runs along the falciform ligament of the liver and then enters the anterior mediastinum by traversing the diaphragm. Inferiorly, the deep lymphatics communicate by coursing to the lymph nodes of the iliac arteries. Because the lymphatic channels of the periumbilical region communicate with the deep inguinal, axillary, deep femoral, and periaortic lymph nodes, once a neoplasm is established at the umbilicus, it can metastasize to any part of the body,8 supporting the notion that the presence of SMJN portends a poor prognosis. In the fetus, the umbilicus serves as the opening for the umbilical vessels. In the adult, there are several ligaments that contain remnants of obliterated fetal structures and connect to the umbilicus. For example, the median umbilical ligament, also known as the urachus, represents the obliterated umbilical arteries that formerly connected the umbilicus to the bladder. The falciform ligament in the adult contains the obliterated umbilical vein and runs along the hepatic surface. Therefore, a firm command of the anatomy and embryology of the periumbilical region is essential for an accurate clinical workup once the diagnosis of SMJN has been established. Physical Examination—Clinically, SMJN usually presents as a firm indurated plaque or nodule that is 0.5 to 2 cm in size, though lesions up to 10 cm have been reported. The lesion is occasionally painful and may have a fibrous consistency with irregular edges that are attached to the anterior abdominal wall. It tends to have a vascular appearance and can be fissured, ulcerated, or necrotic. Purulent discharge may be present if it is secondarily infected. Typically, there are no gross features to distinguish between a primary and secondary umbilical tumor. Differential Diagnosis—The differential diagnosis of SMJN includes a primary carcinoma of the umbilicus, a benign umbilical lesion, and a metastatic lesion of the umbilicus. Primary umbilical carcinomas are rare and include malignant melanoma, basal cell carcinoma, and omphalomesenteric duct carcinoma. Endometriosis is the most common benign lesion of the umbilicus. Other benign umbilical lesions include papillomas, epidermal/inclusion cysts, seborrheic keratoses, dermal nevi, polyps, congenital malformations, foreign bodies, talc granulomas, angiomas, pyogenic and pilonidal granulomas, keloids, incarcerated hernias, angiokeratomas, and lymphangiomas.11 Histopathology—In general, the histology of a cutaneous metastatic lesion is of finite value in determining the site of the primary malignancy. In contrast, when speaking of an umbilical metastasis, histologic sampling more often aids in determining the derivation.11 The histopathology is dependent on the primary tumor and is most often adenocarcinoma, which was the case with our patient. Prognosis—Although the presence of umbilical disease indicates metastasis, it does not suggest unresectability and, in fact, may be the first sign of a recurrence.11 However, in general, SMJN portends a poor prognosis and is considered an ominous sign. The presence of SMJN should prompt a thorough metastatic workup and appropriate clinical staging. Survival time in untreated patients ranges from 2 to 11 months, with 10 months as the average survival time from the appearance of an umbilical metastasis.6,9 This rapid deterioration may be, in part, caused by the rich lymphatic network in the abdominal wall providing communication with the deep inguinal, axillary, deep femoral, and periaortic lymph nodes. Therefore, from the umbilicus, a tumor may spread to many parts of the body.

Conclusion
Cutaneous metastasis is a rare occurrence, making SMJN exceptionally infrequent. The finding of SMJN should prompt a thorough search for the primary malignancy. As demonstrated by our patient, SMJN may be the first sign of a visceral malignancy, making proper and timely diagnosis lifesaving.

A metastatic malignancy of the umbilicus is commonly termed Sister Mary Joseph nodule (SMJN). It is a rare occurrence but may represent the first sign of a visceral malignancy and therefore should prompt a thorough search for the primary tumor. Typically, the most common origin of an umbilical metastasis is an adenocarcinoma from a gastrointestinal or gynecologic primary malignancy. The presence of SMJN carries a poor prognosis with the average survival time at the appearance of an umbilical metastasis being 10 months. We report a case of a 66-year-old man who was referred for evaluation of an enlarging umbilical lesion. Histopathology revealed adenocarcinoma. After a full metastatic workup, the tumor of origin was identified as adenocarcinoma of the sigmoid colon. Benign tumors of the umbilicus are uncommon. This case report serves to emphasize the importance of obtaining a histologic diagnosis when any new lesion presents in the umbilical region.

Case Report
A 66-year-old white man presented for evaluation of an umbilical lesion of 3 weeks' duration. The lesion was asymptomatic and nontender but was bleeding and oozing. The lesion, diagnosed by the patient's primary care physician as an infected pyogenic granuloma, was treated with oral antibiotics, without relief. His past medical history was unremarkable. He took no medications at that time and had an allergy to quinolones. His dermatologic history was positive for numerous actinic keratoses and a basal cell carcinoma on the forehead. Physical examination upon presentation revealed a 3-cm fungating polypoid umbilical mass with copious purulent exudates similar to Figure 1.1 The clinical differential diagnosis at that time included a pyogenic granuloma versus a Sister Mary Joseph nodule (SMJN). A shave biopsy was performed. Histopathology revealed multiple cystic and ductal spaces lined by atypical epithelial cells with numerous mitotic figures in the dermis (Figures 2 and 3). These changes favored a gastrointestinal primary lesion, supporting the clinical diagnosis of SMJN. The patient subsequently underwent a full metastatic workup. A computed tomographic scan of the abdomen and pelvis demonstrated no definite metastases to the lungs or liver but suggested a near-obstructing distal bowel primary tumor. A colonoscopy demonstrated a near-obstructing sigmoid colon carcinoma. The patient subsequently underwent an exploratory laparotomy, sigmoid resection, and primary colonic reanastomosis. Liver biopsies and resection of the omentum and the periumbilical abdominal wall including the eroding metastasis were performed as well as multiple peritoneal biopsies. Pathologic evaluation confirmed the presence of extensive carcinomatosis. The primary tumor was a 5.0X3.0-cm moderately differentiated adenocarcinoma of the sigmoid colon with extension through the bowel wall. Biopsies of the liver, lymph nodes, periumbilical soft tissue, omentum, and peritoneum were all positive for metastatic carcinoma. Postoperatively, the patient was started on the FOLFOX regimen incorporating folinic acid, 5-fluorouracil, and oxaliplatin. Currently, the patient remains clinically stable and without evidence of progressive sigmoid colon carcinoma.

Comment
SMJN is the term applied to an uncommon metastatic malignancy of the umbilicus. This eponym, coined by Sir Hamilton Bailey in his book Physical Signs in Clinical Surgery,2 honors Sister Mary Joseph Dempsey, a nun in the Franciscan order who was the first surgical assistant to Dr. William J. Mayo at St. Mary's Hospital in Rochester, Minnesota.3,4 Sister Mary Joseph made the astute observation that patients with gastrointestinal and gynecologic tumors may have involvement of the umbilicus; if there is involvement of the umbilicus, the prognosis is poor.5 Although Dr. Mayo gives credit to Sister Mary Joseph, contrary to what some believe, he is not responsible for the eponym. Dr. Mayo used the term pants button umbilicus in his article; Sir Bailey definitively coined the term SMJN. Some authors argue that the correct name is Sister Joseph's nodule; however, SMJN remains the more commonly used term.6 Frequency—Cutaneous metastasis, in and of itself, is a rare feature of visceral malignancy, occurring in about 1% to 2% of cases, with umbilical metastasis occurring even less frequently. There are approximately 265 cases of SMJN reported in the literature up to 1990, emphasizing its infrequency. The most common origin of an umbilical metastasis is an adenocarcinoma from a gastrointestinal or gynecologic primary malignancy. In a review of the world literature on metastatic umbilical tumors, Barrow7 found that the most common primary tumor identified was carcinoma of the stomach. The second most common was ovarian tumor,7 with colon, rectal, and pancreatic cancers following in descending order of frequency.8 In very rare cases, the primary tumor involved the breast, cervix, endometrium, small bowel, liver, gallbladder, lung, prostate, kidney, fallopian tube, appendix, and penis.9 In approximately 20% to 30% of cases, the primary tumor could not be identified.9 Umbilical Anatomy—A neoplasm may metastasize to the umbilicus by one of many mechanisms, most commonly direct extension from the anterior peritoneal surface from adjacent organs. Other mechanisms of metastasis include vascular spread via arterial and venous channels, lymphatic spread, and umbilical ligamentous spread. The rich vascular supply to the anterior abdominal wall facilitates metastasis of a neoplasm. The main arteries supplying the umbilical region are the inferior epigastric, deep circumflex iliac, and superior epigastric arteries. Venous drainage of the umbilical region stems from a network of veins radiating from the umbilicus, including the axillary vein above and the femoral vein below the umbilicus. There also are small paraumbilical veins that connect with the portal system along the ligamentum teres hepatis, the superior portion of the falciform ligament.10 The superficial lymphatic drainage of the periumbilical region leads to axillary lymph nodes above and inguinal lymph nodes below the periumbilical region. The deep lymphatic drainage runs along the falciform ligament of the liver and then enters the anterior mediastinum by traversing the diaphragm. Inferiorly, the deep lymphatics communicate by coursing to the lymph nodes of the iliac arteries. Because the lymphatic channels of the periumbilical region communicate with the deep inguinal, axillary, deep femoral, and periaortic lymph nodes, once a neoplasm is established at the umbilicus, it can metastasize to any part of the body,8 supporting the notion that the presence of SMJN portends a poor prognosis. In the fetus, the umbilicus serves as the opening for the umbilical vessels. In the adult, there are several ligaments that contain remnants of obliterated fetal structures and connect to the umbilicus. For example, the median umbilical ligament, also known as the urachus, represents the obliterated umbilical arteries that formerly connected the umbilicus to the bladder. The falciform ligament in the adult contains the obliterated umbilical vein and runs along the hepatic surface. Therefore, a firm command of the anatomy and embryology of the periumbilical region is essential for an accurate clinical workup once the diagnosis of SMJN has been established. Physical Examination—Clinically, SMJN usually presents as a firm indurated plaque or nodule that is 0.5 to 2 cm in size, though lesions up to 10 cm have been reported. The lesion is occasionally painful and may have a fibrous consistency with irregular edges that are attached to the anterior abdominal wall. It tends to have a vascular appearance and can be fissured, ulcerated, or necrotic. Purulent discharge may be present if it is secondarily infected. Typically, there are no gross features to distinguish between a primary and secondary umbilical tumor. Differential Diagnosis—The differential diagnosis of SMJN includes a primary carcinoma of the umbilicus, a benign umbilical lesion, and a metastatic lesion of the umbilicus. Primary umbilical carcinomas are rare and include malignant melanoma, basal cell carcinoma, and omphalomesenteric duct carcinoma. Endometriosis is the most common benign lesion of the umbilicus. Other benign umbilical lesions include papillomas, epidermal/inclusion cysts, seborrheic keratoses, dermal nevi, polyps, congenital malformations, foreign bodies, talc granulomas, angiomas, pyogenic and pilonidal granulomas, keloids, incarcerated hernias, angiokeratomas, and lymphangiomas.11 Histopathology—In general, the histology of a cutaneous metastatic lesion is of finite value in determining the site of the primary malignancy. In contrast, when speaking of an umbilical metastasis, histologic sampling more often aids in determining the derivation.11 The histopathology is dependent on the primary tumor and is most often adenocarcinoma, which was the case with our patient. Prognosis—Although the presence of umbilical disease indicates metastasis, it does not suggest unresectability and, in fact, may be the first sign of a recurrence.11 However, in general, SMJN portends a poor prognosis and is considered an ominous sign. The presence of SMJN should prompt a thorough metastatic workup and appropriate clinical staging. Survival time in untreated patients ranges from 2 to 11 months, with 10 months as the average survival time from the appearance of an umbilical metastasis.6,9 This rapid deterioration may be, in part, caused by the rich lymphatic network in the abdominal wall providing communication with the deep inguinal, axillary, deep femoral, and periaortic lymph nodes. Therefore, from the umbilicus, a tumor may spread to many parts of the body.

Conclusion
Cutaneous metastasis is a rare occurrence, making SMJN exceptionally infrequent. The finding of SMJN should prompt a thorough search for the primary malignancy. As demonstrated by our patient, SMJN may be the first sign of a visceral malignancy, making proper and timely diagnosis lifesaving.