- Email: [email protected]
Diverticulitis: An inciting factor in erythema nodosum
J AM ACAD DERMATOL
e60 Letters
JULY 2012
2. Kayal JD, Hampton RW, Sheehan DJ, Washington CV. Malignant glomus tumor: a case report and review of the literature. Dermatol Surg 2001;27:837-40. 3. Drape J, Idy-Peretti I, Goettmann S, Guerin-Surville H, Bittoun J. Standard and high resolution magnetic resonance imaging of glomus tumors of toes and fingertips. J Am Acad Dermatol 1996;35:550-5. 4. Takemura N, Fujii N, Tanaka T. Subungual glomus tumor diagnosis based on imaging. J Dermatol 2006;35:389-93. 5. Lin YC, Hsiao PF, Wu YH, Sun FJ, Scher RK. Recurrent digital glomus tumor: analysis of 75 cases. Dermatol Surg 2010;36:1396-400. 6. Chen SH, Chen YL, Cheng MH, Yeow KM, Chen HC, Wei FC. The use of ultrasonography in preoperative localization of digital glomus tumors. Plast Reconstr Surg 2003;112:115-9.
Fig 1. Erythematous subcutaneous nodule of left shin.
doi:10.1016/j.jaad.2011.01.011
Diverticulitis: An inciting factor in erythema nodosum To the Editor: A 55-year-old woman with diverticulosis had acute onset of red nodules on her lower extremities associated with fever and arthralgias (Fig 1). Within weeks, she developed nausea, diarrhea, and hematochezia. A colonoscopy to investigate her symptoms showed chronic inflammation. Skin biopsy specimen of a nodule showed mixed lobular and septal suppurative panniculitis with negative Fite, acid-fast bacilli, and Gomori methenamine silver stains. Bacterial, fungal, and atypical mycobacterial tissue cultures were negative. Her history of recently swimming in a lake raised the possibility of an atypical mycobacterial infection.
Because of suspicion for an infectious panniculitis, empiric treatment was initiated for atypical mycobacterial infection. Antibiotics initially suppressed the inflammatory nodules, but they recurred. Repeated skin biopsy specimen of a lower extremity nodule showed findings diagnostic of erythema nodosum (EN) (Fig 2). These included a mainly septal panniculitis, with fibrosis and widening of subcutaneous septa, and an infiltrate of lymphocytes, eosinophils, and a small periseptal granuloma. Treatment of her EN included potassium iodide and indomethacin. Over the next 2 years, she continued to have episodes of tender shin nodules accompanied by fever, arthralgias, and episcleritis. A complete autoimmune workup revealed negative findings. Given continued gastrointestinal symptoms,
Fig 2. Erythema nodosum on biopsy specimen. A, Punch biopsy specimen demonstrates largely septal panniculitis, with widening and fibrosis of septa, with limited dermal infiltrate. B, Subcutaneous infiltrate contains lymphocytes, eosinophils, and histiocytes, concentrated near septae, with small periseptal granuloma. (A and B, Hematoxylin-eosin stain; original magnifications: A, 3 20; B, 3 200.)
J AM ACAD DERMATOL
Letters e61
VOLUME 67, NUMBER 1
Table I. Gastrointestinal etiologic factors of erythema nodosum1 Infectious
Bacterial Brucellosis Campylobacter Escherichia coli Salmonella Shigella Yersinia Protozoal Giardiasis Hookworm Amebiasis Ascariasis
Malignancy
Stomach cancer Colon adenocarcinoma Pancreatic carcinoma
Hepatic
Hepatitis B, C Hydatidosis Primary biliary cirrhosis Carcinoid tumor Hepatocellular carcinoma
Other
Celiac disease Colon diverticulosis/diverticulitis IBD (Crohn’s, ulcerative colitis) Bowel bypass
IBD, Inflammatory bowel disease.
a repeated gastrointestinal workup was initiated to search for an underlying cause of her EN, specifically inflammatory bowel disease (IBD). Computed tomography scan of the abdomen and pelvis showed a colonic abscess in the setting of diverticulitis. Interventional radiology-guided abscess drainage revealed methicillin-resistant Staphylococcus aureus. She completed a course of targeted therapy with trimethoprim-sulfamethoxazole and underwent resection of the diverticulum for definitive treatment. Over the next 5 months, the number and frequency of nodules continued to decrease. Seven months later, she remains free of EN with resolution of diverticulitis. This case demonstrates that early lesions can be suppurative with lobular involvement, such that the differential diagnosis remains broad. Once the diagnosis of EN has been made, possible inciting factors are numerous. EN has been linked to various gastrointestinal diseases, including infections, IBD, malignancy, and hepatic disease (Table I).1 The established connection between EN and IBD lends credence to the possible association between other inflammatory gastrointestinal conditions such as diverticulitis.2 Of people older than 60 years, 40% have diverticula. Up to 25% of these patients may undergo inflammatory changes secondary to obstruction, stasis, altered local flora, or ischemia, resulting in diverticulitis. A frequent complication is pericolonic abscess formation.3 A subset of persons with IBD may have a genetic susceptibility to developing extraintestinal manifestations. EN has been associated with CARD15 polymorphisms in patients with Crohn’s. CARD15 is a caspase recruitment domain protein that recognizes muramyl dipeptide found in specific bacteria.4 This suggests that the susceptible host interaction of the immune system with specific antigens on
gastrointestinal flora, as would occur in the inflammatory milieu in diverticulitis, could possibly trigger EN.5 EN is a relatively common skin finding with numerous triggers, including gastrointestinal conditions. Our case demonstrates the association between the two common diseases: EN and diverticulitis. Dermatologists should consider diverticulitis as a cause of EN in the appropriate patient. Tracie Ann Chong, BA,a Nina K. Hansra, MD,b Beth S. Ruben, MD,b,c and Timothy G. Berger, MDb School of Medicine, University of Hawaii John A. Burns School of Medicine, Honolulua; and Departments of Dermatologyb and Pathology,c University of California, San Francisco Funding sources: None. Conflicts of interest: None declared. Correspondence to: Timothy G. Berger, MD, Department of Dermatology, University of California, San Francisco, Box 0316, 1701 Divisadero St, 340, San Francisco, CA 94143-0316. E-mail: [email protected] REFERENCES 1. Cribier B, Caille A, Heid E, Grosshans E. Erythema nodosum and associated diseases: a study of 129 cases. Int J Dermatol 1998;37:667-72. 2. McCallum DI, Kinmont PD. Dermatological manifestations of Crohn’s disease. Br J Dermatol 1968;80:1-8. 3. Touzios JG, Dozois EJ. Diverticulosis and acute diverticulitis. Gastroenterol Clin North Am 2009;38:513-25. 4. Barreiro-de Acosta M, Dominguez-Munoz JE, Nunez-Pardo de Vera MC, Lozano-Le on A, Lorenzo A, Pe~ na S, et al. Relationship between clinical features of Crohn’s disease and the risk of developing extraintestinal manifestations. Eur J Gastroenterol Hepatol 2007;19:73-8.
J AM ACAD DERMATOL
e62 Letters
JULY 2012
5. Farhi D, Cosnes J, Zizi N, Chosidow O, Seksik P, Beaugerie L, et al. Significance of erythema nodosum and pyoderma gangrenosum in inflammatory bowel diseases: a cohort study of 2402 patients. Medicine (Baltimore) 2008;87:281-93.
doi:10.1016/j.jaad.2011.08.013
Multifocal lymphangioendotheliomatosis with thrombocytopenia: Phenotypic variant and course with propranolol, corticosteroids, and aminocaproic acid To the Editor: A 6-week-old girl had numerous firm, noncompressible blue or violet plaques and nodules (Fig 1, A and B), present since birth. Her prenatal course and family history were unremarkable. She was anemic (Hg ¼ 6.8 g/dL; normal range, 9-14 g/dL) with thrombocytopenia ( platelet nadir, 174 3 109/L; normal range, 300e750 3 109/L), low serum fibrinogen (107 mg/dL; normal range, 230-450 mg/dL), and
elevated D-dimer level ([20 g/mL; normal \0.5 g/mL), indicating a consumptive coagulopathy. A primary hematopoietic or infectious process was excluded. Analysis of nasogastric contents, serial stool guaiac tests, and abdominal imaging did not reveal gastrointestinal bleeding. She developed facial hemiparesis and brain magnetic resonance (MR) arteriography/venography showed foci of intraparenchymal hemorrhage without evidence of an arteriovenous or venous malformation (Fig 1, C ). She received multiple transfusions of erythrocytes (4), fresh-frozen plasma (1), and cryoprecipitate (4) during the first 2 weeks of hospitalization. Histopathologic examination of a lesional skin biopsy specimen from the right side of her chest showed expansion of the dermis and subcutis by large ectatic, thin-walled vascular spaces, focally containing erythrocytes and organizing thrombi (Fig 2). The vascular spaces were lined by enlarged epithelioid and hobnailed endothelial cells forming
Fig 1. Multifocal lymphangioendotheliomatosis with thrombocytopenia. Cutaneous vascular lesions (A and B); and coronal T2 brain magnetic resonance (MR) imaging (C) at 6 weeks of age showing intraparenchymal hemorrhagic foci in the right midbrain and left frontoparietal lobes with surrounding edema and mass effect without evidence of arteriovenous or venous malformations on simultaneous arteriography (MRA) and venography (MRV). Follow-up clinical and T2 brain MR images (D-F) at 8 months of age with regression of skin lesions and nearly complete resolution of brain hemorrhages during treatment with propranolol, prednisolone, and aminocaproic acid. A residual vascular lesion in the right midbrain is evidenced by the completely hypointense hemosiderin ring without mass effect.
e60 Letters
JULY 2012
2. Kayal JD, Hampton RW, Sheehan DJ, Washington CV. Malignant glomus tumor: a case report and review of the literature. Dermatol Surg 2001;27:837-40. 3. Drape J, Idy-Peretti I, Goettmann S, Guerin-Surville H, Bittoun J. Standard and high resolution magnetic resonance imaging of glomus tumors of toes and fingertips. J Am Acad Dermatol 1996;35:550-5. 4. Takemura N, Fujii N, Tanaka T. Subungual glomus tumor diagnosis based on imaging. J Dermatol 2006;35:389-93. 5. Lin YC, Hsiao PF, Wu YH, Sun FJ, Scher RK. Recurrent digital glomus tumor: analysis of 75 cases. Dermatol Surg 2010;36:1396-400. 6. Chen SH, Chen YL, Cheng MH, Yeow KM, Chen HC, Wei FC. The use of ultrasonography in preoperative localization of digital glomus tumors. Plast Reconstr Surg 2003;112:115-9.
Fig 1. Erythematous subcutaneous nodule of left shin.
doi:10.1016/j.jaad.2011.01.011
Diverticulitis: An inciting factor in erythema nodosum To the Editor: A 55-year-old woman with diverticulosis had acute onset of red nodules on her lower extremities associated with fever and arthralgias (Fig 1). Within weeks, she developed nausea, diarrhea, and hematochezia. A colonoscopy to investigate her symptoms showed chronic inflammation. Skin biopsy specimen of a nodule showed mixed lobular and septal suppurative panniculitis with negative Fite, acid-fast bacilli, and Gomori methenamine silver stains. Bacterial, fungal, and atypical mycobacterial tissue cultures were negative. Her history of recently swimming in a lake raised the possibility of an atypical mycobacterial infection.
Because of suspicion for an infectious panniculitis, empiric treatment was initiated for atypical mycobacterial infection. Antibiotics initially suppressed the inflammatory nodules, but they recurred. Repeated skin biopsy specimen of a lower extremity nodule showed findings diagnostic of erythema nodosum (EN) (Fig 2). These included a mainly septal panniculitis, with fibrosis and widening of subcutaneous septa, and an infiltrate of lymphocytes, eosinophils, and a small periseptal granuloma. Treatment of her EN included potassium iodide and indomethacin. Over the next 2 years, she continued to have episodes of tender shin nodules accompanied by fever, arthralgias, and episcleritis. A complete autoimmune workup revealed negative findings. Given continued gastrointestinal symptoms,
Fig 2. Erythema nodosum on biopsy specimen. A, Punch biopsy specimen demonstrates largely septal panniculitis, with widening and fibrosis of septa, with limited dermal infiltrate. B, Subcutaneous infiltrate contains lymphocytes, eosinophils, and histiocytes, concentrated near septae, with small periseptal granuloma. (A and B, Hematoxylin-eosin stain; original magnifications: A, 3 20; B, 3 200.)
J AM ACAD DERMATOL
Letters e61
VOLUME 67, NUMBER 1
Table I. Gastrointestinal etiologic factors of erythema nodosum1 Infectious
Bacterial Brucellosis Campylobacter Escherichia coli Salmonella Shigella Yersinia Protozoal Giardiasis Hookworm Amebiasis Ascariasis
Malignancy
Stomach cancer Colon adenocarcinoma Pancreatic carcinoma
Hepatic
Hepatitis B, C Hydatidosis Primary biliary cirrhosis Carcinoid tumor Hepatocellular carcinoma
Other
Celiac disease Colon diverticulosis/diverticulitis IBD (Crohn’s, ulcerative colitis) Bowel bypass
IBD, Inflammatory bowel disease.
a repeated gastrointestinal workup was initiated to search for an underlying cause of her EN, specifically inflammatory bowel disease (IBD). Computed tomography scan of the abdomen and pelvis showed a colonic abscess in the setting of diverticulitis. Interventional radiology-guided abscess drainage revealed methicillin-resistant Staphylococcus aureus. She completed a course of targeted therapy with trimethoprim-sulfamethoxazole and underwent resection of the diverticulum for definitive treatment. Over the next 5 months, the number and frequency of nodules continued to decrease. Seven months later, she remains free of EN with resolution of diverticulitis. This case demonstrates that early lesions can be suppurative with lobular involvement, such that the differential diagnosis remains broad. Once the diagnosis of EN has been made, possible inciting factors are numerous. EN has been linked to various gastrointestinal diseases, including infections, IBD, malignancy, and hepatic disease (Table I).1 The established connection between EN and IBD lends credence to the possible association between other inflammatory gastrointestinal conditions such as diverticulitis.2 Of people older than 60 years, 40% have diverticula. Up to 25% of these patients may undergo inflammatory changes secondary to obstruction, stasis, altered local flora, or ischemia, resulting in diverticulitis. A frequent complication is pericolonic abscess formation.3 A subset of persons with IBD may have a genetic susceptibility to developing extraintestinal manifestations. EN has been associated with CARD15 polymorphisms in patients with Crohn’s. CARD15 is a caspase recruitment domain protein that recognizes muramyl dipeptide found in specific bacteria.4 This suggests that the susceptible host interaction of the immune system with specific antigens on
gastrointestinal flora, as would occur in the inflammatory milieu in diverticulitis, could possibly trigger EN.5 EN is a relatively common skin finding with numerous triggers, including gastrointestinal conditions. Our case demonstrates the association between the two common diseases: EN and diverticulitis. Dermatologists should consider diverticulitis as a cause of EN in the appropriate patient. Tracie Ann Chong, BA,a Nina K. Hansra, MD,b Beth S. Ruben, MD,b,c and Timothy G. Berger, MDb School of Medicine, University of Hawaii John A. Burns School of Medicine, Honolulua; and Departments of Dermatologyb and Pathology,c University of California, San Francisco Funding sources: None. Conflicts of interest: None declared. Correspondence to: Timothy G. Berger, MD, Department of Dermatology, University of California, San Francisco, Box 0316, 1701 Divisadero St, 340, San Francisco, CA 94143-0316. E-mail: [email protected] REFERENCES 1. Cribier B, Caille A, Heid E, Grosshans E. Erythema nodosum and associated diseases: a study of 129 cases. Int J Dermatol 1998;37:667-72. 2. McCallum DI, Kinmont PD. Dermatological manifestations of Crohn’s disease. Br J Dermatol 1968;80:1-8. 3. Touzios JG, Dozois EJ. Diverticulosis and acute diverticulitis. Gastroenterol Clin North Am 2009;38:513-25. 4. Barreiro-de Acosta M, Dominguez-Munoz JE, Nunez-Pardo de Vera MC, Lozano-Le on A, Lorenzo A, Pe~ na S, et al. Relationship between clinical features of Crohn’s disease and the risk of developing extraintestinal manifestations. Eur J Gastroenterol Hepatol 2007;19:73-8.
J AM ACAD DERMATOL
e62 Letters
JULY 2012
5. Farhi D, Cosnes J, Zizi N, Chosidow O, Seksik P, Beaugerie L, et al. Significance of erythema nodosum and pyoderma gangrenosum in inflammatory bowel diseases: a cohort study of 2402 patients. Medicine (Baltimore) 2008;87:281-93.
doi:10.1016/j.jaad.2011.08.013
Multifocal lymphangioendotheliomatosis with thrombocytopenia: Phenotypic variant and course with propranolol, corticosteroids, and aminocaproic acid To the Editor: A 6-week-old girl had numerous firm, noncompressible blue or violet plaques and nodules (Fig 1, A and B), present since birth. Her prenatal course and family history were unremarkable. She was anemic (Hg ¼ 6.8 g/dL; normal range, 9-14 g/dL) with thrombocytopenia ( platelet nadir, 174 3 109/L; normal range, 300e750 3 109/L), low serum fibrinogen (107 mg/dL; normal range, 230-450 mg/dL), and
elevated D-dimer level ([20 g/mL; normal \0.5 g/mL), indicating a consumptive coagulopathy. A primary hematopoietic or infectious process was excluded. Analysis of nasogastric contents, serial stool guaiac tests, and abdominal imaging did not reveal gastrointestinal bleeding. She developed facial hemiparesis and brain magnetic resonance (MR) arteriography/venography showed foci of intraparenchymal hemorrhage without evidence of an arteriovenous or venous malformation (Fig 1, C ). She received multiple transfusions of erythrocytes (4), fresh-frozen plasma (1), and cryoprecipitate (4) during the first 2 weeks of hospitalization. Histopathologic examination of a lesional skin biopsy specimen from the right side of her chest showed expansion of the dermis and subcutis by large ectatic, thin-walled vascular spaces, focally containing erythrocytes and organizing thrombi (Fig 2). The vascular spaces were lined by enlarged epithelioid and hobnailed endothelial cells forming
Fig 1. Multifocal lymphangioendotheliomatosis with thrombocytopenia. Cutaneous vascular lesions (A and B); and coronal T2 brain magnetic resonance (MR) imaging (C) at 6 weeks of age showing intraparenchymal hemorrhagic foci in the right midbrain and left frontoparietal lobes with surrounding edema and mass effect without evidence of arteriovenous or venous malformations on simultaneous arteriography (MRA) and venography (MRV). Follow-up clinical and T2 brain MR images (D-F) at 8 months of age with regression of skin lesions and nearly complete resolution of brain hemorrhages during treatment with propranolol, prednisolone, and aminocaproic acid. A residual vascular lesion in the right midbrain is evidenced by the completely hypointense hemosiderin ring without mass effect.