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Recalcitrant necrobiotic xanthogranuloma responding to infliximab
P570
P572
RECALCITRANT NECROBIOTIC XANTHOGRANULOMA RESPONDING TO INFLIXIMAB John Kraft, BSc, Carolyn Lynde, BSc, Charles Lynde, BSc, MD, University of Toronto, Toronto, ON, Canada; Ron Mahler, MD, Thunder Bay private practice, Thunder Bay, ON, Canada
SARCOIDOSIS ASSOCIATED WITH HYPERTROPHIC LICHEN PLANUS Claudia DeGiovanni, MBBS, Arjida Woollons, MD, Dermatology Department, Worthing and Southlands NHS Trust, Shoreham-by-Sea, England Sarcoidosis and lichen planus are well-described conditions; the underlying aetiologies for both, however, are still poorly understood. There are many documented associations. Sarcoid has been described in patients with autoimmune, connective tissue, and neoplastic disorders, and it has been associated with various medications. Lichen planus has been associated with autoimmune disorders, hepatitis C infection, morphoea, and ulcerative colitis. We present a case report of sarcoidosis and lichen planus occurring together. A 53-year-old gentleman attended the Dermatology Clinic with a 4-month history of violaceous pruritic nodules on his shins. He was diagnosed with pulmonary sarcoidosis on transbronchial biopsies in 1999.
Introduction: Necrobiotic xanthogranuloma (NXG) is a distinct clinical and pathologic entity first described by Kossard and Winkelmann in 1980. This rare disorder is characterized by multiple yellowish red nodules or plaques, often ulcerated, which progress through inflammatory episodes toward atrophy. The cutaneous lesions are often associated with paraproteinemia, a lymphoproliferative disorder, or both. Case report and methods: We describe a 54-year-old man who has widespread, yellowish red nodules and plaques involving the face, torso, and limbs that have been present since 1997. In particular, he has had significant periorbital involvement. Skin biopsies revealed typical findings of necrobiotic xanthogranuloma. A discrete gammopathy/paraproteinemia was found on subsequent investigation. This patient’s rare disease posed a therapeutic challenge. A search of the literature was conducted on Ovid MEDLINE, including all articles in the database from 1966 to June 2004 using ‘‘necrobiotic xanthogranuloma’’ as a keyword. Results: Seventy-nine papers (55 individually reported cases), primarily case reports, were ascertained and reviewed. To date, the clinical reviews have mainly focused on the clinical and pathological features of this rare disease and do not give clear guidance for treatment. Conclusions: Our patient has had several of the suggested therapeutic regimens, including oral steroids, acitretin, methotrexate, PUVA, pentoxifylline, potassium iodide, and intralesional steroids. Despite these therapeutic interventions, our patient’s disease has not improved but progressed. No clear-cut therapeutic regimen was ascertained from the literature. We have attempted to rank the relative success of each of the suggested regimens and propose a new therapeutic option, infliximab, for this disease. Given the extensive role of macrophages in the pathogenesis of NXG and in view of the reported favorable results of infliximab in treating necrobiosis lipoidica diabeticorum (NLD), we investigated the efficacy of this anti-tumor necrosis factor-a biological drug in treating our patient. After 3 courses and 2 weeks, a period longer than the typical psoriatic or NLD response to infliximab, it appeared as though our patient was not responding. However, 1 month later, our patient with NXG was responding and continues to improve with additional courses of infliximab. To our knowledge, this is the first patient with NXG to be given infliximab.
Examination revealed dermal nodules, which were consistent with cutaneous sarcoid. A skin biopsy showed epidermal acanthosis with overlying hyperkeratosis, a mild chronic inflammatory cell infiltrate of the upper dermis, and focal liquefaction degeneration of the basal layers. The appearances were consistent with a diagnosis of hypertrophic lichen planus. A repeat biopsy confirmed hypertrophic lichen planus with no evidence of sarcoid granulomas. The patient responded well to oral prednisolone. Both sarcoidosis and lichen planus are disorders of unknown aetiology. Glass and Apisarnthanarx described a case of verrucous sarcoidosis simulating hypertrophic lichen planus though a biopsy demonstrated non-caseating granulomas. Goldberg et al presented 3 cases of giant cell lichenoid dermatitis, one of which also had granulomatous uveitis and was treated for sarcoid. Though both sarcoid and lichen planus have been associated with many other disorders, to our knowledge there is only one report from 1961 of the two conditions occurring together. Further studies aimed at evaluating this association may give us further insight into the underlying pathogenesis of these poorly understood conditions. Nothing to disclose.
Dr. Charles Lynde conducts clinical studies for Centocor.
P573
P571 RECURRENT PANCREATIC PANNICULITIS Jennifer Jones, MBBS, Raymond Yu, MBBS, MD, J. Shankar, MBBS, MD, University College of London, London, England A 56-year-old man with acute pancreatitis due to gallstones was referred to the dermatology service with a 4-week history of red tender nodules on his shins. He was not taking any medication and had no other history of note. Investigations revealed an increased amylase level at 948 IU/L. All other blood tests, including glucose, calcium, and a1-antitrypsin levels, were normal. A biopsy of one of the lesions was carried out and revealed a mixed septal and lobular panniculitis with a predominantly lobular picture, giant cells, and fat necrosis consistent with pancreatic panniculitis. The patient underwent cholecystectomy, which resulted in resolution of his symptoms. CT scan of his abdomen revealed a pseudocyst in the tail of the pancreas. One year later he was re-referred to dermatology with a recurrence of red tender nodules on the lower legs. He otherwise felt completely well. Oral steroids were considered as treatment for the panniculitis. Repeat blood tests were carried out before treatment and found to be normal apart from a grossly raised serum amylase level at 3865 IU/L, which, given that he was free of symptoms, would suggest silent acute pancreatitis. Subcutaneous nodular fat necrosis is a rare dermatological manifestation of pancreatitis, pancreatic pseudocyst, or carcinoma and may predate clinical symptoms. It is thought, at least partially, to be due to circulating pancreatic enzymes such as lipase, amylase, and trypsin. It is clinically identical to erythema nodosum; therefore a biopsy is necessary to make the diagnosis. In about 2% of cases, acute pancreatitis may be clinically silent so that panniculitis may be an unusual presenting complaint of this relatively common disease. It may also be indicative, as in our patient, of a relapsing pancreatitis or pseudocyst and should prompt investigation of a possible underlying adenocarcinoma of the pancreas. Nothing to disclose.
MARCH 2005
SLEEP MAINTENANCE DIFFICULTIES ARE ASSOCITED WITH A HIGHER FREQUENCY OF PRURITUS: A STUDY OF NONCLINICAL SUBJECTS Madhulika Gupta, MD, Department of Psychiatry, University of Western Ontario, London, ON, Canada; Aditya Gupta, MD, PhD, Division of Dermatology, Department of Medicine, University of Toronto, Toronto, ON, Canada Background: Pruritus is one of the most common dermatologic symptoms associated with significant morbidity. Sleep disturbance can modulate and/or amplify pruritus perception in a wide range of pruritic skin disorders. A better understanding of the modulating effect of sleep on pruritus may therefore be of help in the management of pruritus. Purpose: We examined the relation between difficulties with maintenance of sleep and pruritus-related symptoms in a nonclinical sample. Methods: Three hundred sixty-two consenting nonclinical subjects [271 women and 91 men; mean (SD) age 38.4 (14.5) years; race: 92% white] from the community at large in London, Ontario, Canada completed a battery of questionnaires including items on sleep and pruritus ratings. Exclusion criteria were the presence of any dermatologic or medical disorder. The sleep-related ratings were as follows: subjects rated how many times they usually awaken during the night by checking one of 4 boxes labelled as ‘‘None,’’ ‘‘1 to 2 times,’’ ‘‘3 to 4 times,’’ and ‘‘5 or more times.’’ Secondly, they rated how often they experienced pruritus during their sleep. Pruritus experienced over the previous 1 month was rated on a 10-point rating scale (a rating of ‘‘0’’ denoted ‘‘not at all’’ and a rating of ‘‘9’’ denoted ‘‘very markedly’’). Results: There was a direct correlation between the degree of disruption of sleep and pruritus severity (Pearson r = 0.26, P \.001). When the potential confounding effect of pruritus on sleep maintenance was partialled out statistically, the correlation between sleep disruption and pruritus remained significant (partial r = 0.18, P = .001). Comment: Our preliminary findings among a nonclincal sample which explicitly excluded dermatologic patients indicates a direct correlation between the severity of sleep maintenance difficulties and the severity of pruritus, which was present even after the possible confounding effect of pruritus on sleep was controlled for statistically. Sleep disruption may decrease the threshold for pruritus. Nothing to disclose.
J AM ACAD DERMATOL
P59
P572
RECALCITRANT NECROBIOTIC XANTHOGRANULOMA RESPONDING TO INFLIXIMAB John Kraft, BSc, Carolyn Lynde, BSc, Charles Lynde, BSc, MD, University of Toronto, Toronto, ON, Canada; Ron Mahler, MD, Thunder Bay private practice, Thunder Bay, ON, Canada
SARCOIDOSIS ASSOCIATED WITH HYPERTROPHIC LICHEN PLANUS Claudia DeGiovanni, MBBS, Arjida Woollons, MD, Dermatology Department, Worthing and Southlands NHS Trust, Shoreham-by-Sea, England Sarcoidosis and lichen planus are well-described conditions; the underlying aetiologies for both, however, are still poorly understood. There are many documented associations. Sarcoid has been described in patients with autoimmune, connective tissue, and neoplastic disorders, and it has been associated with various medications. Lichen planus has been associated with autoimmune disorders, hepatitis C infection, morphoea, and ulcerative colitis. We present a case report of sarcoidosis and lichen planus occurring together. A 53-year-old gentleman attended the Dermatology Clinic with a 4-month history of violaceous pruritic nodules on his shins. He was diagnosed with pulmonary sarcoidosis on transbronchial biopsies in 1999.
Introduction: Necrobiotic xanthogranuloma (NXG) is a distinct clinical and pathologic entity first described by Kossard and Winkelmann in 1980. This rare disorder is characterized by multiple yellowish red nodules or plaques, often ulcerated, which progress through inflammatory episodes toward atrophy. The cutaneous lesions are often associated with paraproteinemia, a lymphoproliferative disorder, or both. Case report and methods: We describe a 54-year-old man who has widespread, yellowish red nodules and plaques involving the face, torso, and limbs that have been present since 1997. In particular, he has had significant periorbital involvement. Skin biopsies revealed typical findings of necrobiotic xanthogranuloma. A discrete gammopathy/paraproteinemia was found on subsequent investigation. This patient’s rare disease posed a therapeutic challenge. A search of the literature was conducted on Ovid MEDLINE, including all articles in the database from 1966 to June 2004 using ‘‘necrobiotic xanthogranuloma’’ as a keyword. Results: Seventy-nine papers (55 individually reported cases), primarily case reports, were ascertained and reviewed. To date, the clinical reviews have mainly focused on the clinical and pathological features of this rare disease and do not give clear guidance for treatment. Conclusions: Our patient has had several of the suggested therapeutic regimens, including oral steroids, acitretin, methotrexate, PUVA, pentoxifylline, potassium iodide, and intralesional steroids. Despite these therapeutic interventions, our patient’s disease has not improved but progressed. No clear-cut therapeutic regimen was ascertained from the literature. We have attempted to rank the relative success of each of the suggested regimens and propose a new therapeutic option, infliximab, for this disease. Given the extensive role of macrophages in the pathogenesis of NXG and in view of the reported favorable results of infliximab in treating necrobiosis lipoidica diabeticorum (NLD), we investigated the efficacy of this anti-tumor necrosis factor-a biological drug in treating our patient. After 3 courses and 2 weeks, a period longer than the typical psoriatic or NLD response to infliximab, it appeared as though our patient was not responding. However, 1 month later, our patient with NXG was responding and continues to improve with additional courses of infliximab. To our knowledge, this is the first patient with NXG to be given infliximab.
Examination revealed dermal nodules, which were consistent with cutaneous sarcoid. A skin biopsy showed epidermal acanthosis with overlying hyperkeratosis, a mild chronic inflammatory cell infiltrate of the upper dermis, and focal liquefaction degeneration of the basal layers. The appearances were consistent with a diagnosis of hypertrophic lichen planus. A repeat biopsy confirmed hypertrophic lichen planus with no evidence of sarcoid granulomas. The patient responded well to oral prednisolone. Both sarcoidosis and lichen planus are disorders of unknown aetiology. Glass and Apisarnthanarx described a case of verrucous sarcoidosis simulating hypertrophic lichen planus though a biopsy demonstrated non-caseating granulomas. Goldberg et al presented 3 cases of giant cell lichenoid dermatitis, one of which also had granulomatous uveitis and was treated for sarcoid. Though both sarcoid and lichen planus have been associated with many other disorders, to our knowledge there is only one report from 1961 of the two conditions occurring together. Further studies aimed at evaluating this association may give us further insight into the underlying pathogenesis of these poorly understood conditions. Nothing to disclose.
Dr. Charles Lynde conducts clinical studies for Centocor.
P573
P571 RECURRENT PANCREATIC PANNICULITIS Jennifer Jones, MBBS, Raymond Yu, MBBS, MD, J. Shankar, MBBS, MD, University College of London, London, England A 56-year-old man with acute pancreatitis due to gallstones was referred to the dermatology service with a 4-week history of red tender nodules on his shins. He was not taking any medication and had no other history of note. Investigations revealed an increased amylase level at 948 IU/L. All other blood tests, including glucose, calcium, and a1-antitrypsin levels, were normal. A biopsy of one of the lesions was carried out and revealed a mixed septal and lobular panniculitis with a predominantly lobular picture, giant cells, and fat necrosis consistent with pancreatic panniculitis. The patient underwent cholecystectomy, which resulted in resolution of his symptoms. CT scan of his abdomen revealed a pseudocyst in the tail of the pancreas. One year later he was re-referred to dermatology with a recurrence of red tender nodules on the lower legs. He otherwise felt completely well. Oral steroids were considered as treatment for the panniculitis. Repeat blood tests were carried out before treatment and found to be normal apart from a grossly raised serum amylase level at 3865 IU/L, which, given that he was free of symptoms, would suggest silent acute pancreatitis. Subcutaneous nodular fat necrosis is a rare dermatological manifestation of pancreatitis, pancreatic pseudocyst, or carcinoma and may predate clinical symptoms. It is thought, at least partially, to be due to circulating pancreatic enzymes such as lipase, amylase, and trypsin. It is clinically identical to erythema nodosum; therefore a biopsy is necessary to make the diagnosis. In about 2% of cases, acute pancreatitis may be clinically silent so that panniculitis may be an unusual presenting complaint of this relatively common disease. It may also be indicative, as in our patient, of a relapsing pancreatitis or pseudocyst and should prompt investigation of a possible underlying adenocarcinoma of the pancreas. Nothing to disclose.
MARCH 2005
SLEEP MAINTENANCE DIFFICULTIES ARE ASSOCITED WITH A HIGHER FREQUENCY OF PRURITUS: A STUDY OF NONCLINICAL SUBJECTS Madhulika Gupta, MD, Department of Psychiatry, University of Western Ontario, London, ON, Canada; Aditya Gupta, MD, PhD, Division of Dermatology, Department of Medicine, University of Toronto, Toronto, ON, Canada Background: Pruritus is one of the most common dermatologic symptoms associated with significant morbidity. Sleep disturbance can modulate and/or amplify pruritus perception in a wide range of pruritic skin disorders. A better understanding of the modulating effect of sleep on pruritus may therefore be of help in the management of pruritus. Purpose: We examined the relation between difficulties with maintenance of sleep and pruritus-related symptoms in a nonclinical sample. Methods: Three hundred sixty-two consenting nonclinical subjects [271 women and 91 men; mean (SD) age 38.4 (14.5) years; race: 92% white] from the community at large in London, Ontario, Canada completed a battery of questionnaires including items on sleep and pruritus ratings. Exclusion criteria were the presence of any dermatologic or medical disorder. The sleep-related ratings were as follows: subjects rated how many times they usually awaken during the night by checking one of 4 boxes labelled as ‘‘None,’’ ‘‘1 to 2 times,’’ ‘‘3 to 4 times,’’ and ‘‘5 or more times.’’ Secondly, they rated how often they experienced pruritus during their sleep. Pruritus experienced over the previous 1 month was rated on a 10-point rating scale (a rating of ‘‘0’’ denoted ‘‘not at all’’ and a rating of ‘‘9’’ denoted ‘‘very markedly’’). Results: There was a direct correlation between the degree of disruption of sleep and pruritus severity (Pearson r = 0.26, P \.001). When the potential confounding effect of pruritus on sleep maintenance was partialled out statistically, the correlation between sleep disruption and pruritus remained significant (partial r = 0.18, P = .001). Comment: Our preliminary findings among a nonclincal sample which explicitly excluded dermatologic patients indicates a direct correlation between the severity of sleep maintenance difficulties and the severity of pruritus, which was present even after the possible confounding effect of pruritus on sleep was controlled for statistically. Sleep disruption may decrease the threshold for pruritus. Nothing to disclose.
J AM ACAD DERMATOL
P59