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The polymorphic nature of paraneoplastic pemphigus: A case report
INFECTION (BACTERIAL)
P1620 Biopsy proven cicatricial pemphigoid from uninvolved oral mucosae Laura Ganger, MD, Henry Ford Hospital Department of Dermatology, Detroit, MI, United States; Iltefat Hamzavi, MD, Henry Ford Hospital Department of Dermatology, Detroit, MI, United States Background and objective: Cicatricial pemphigoid is a chronic and often disabling disease. This condition tends to affect mostly the mucous membranes including the oral and conjunctival mucosae. Erosive desquamative gingivitis is a common oral presentation. Conjunctival involvement may result in blindness. Ocular involvement starts as a non-specific, chronic conjunctivitis, with burning, soreness, foreignbody sensation, or mucous production. Symblepharon formation is a common manifestation. Materials and methods: This is a case report of a patient with a 7-month history of grittiness and symblepharon of the left eye. He denied any involvement of the oral mucosae. The left conjunctivae was biopsied and was most likely consistent with cicatricial pemphigoid; however, the pathology was inconclusive. The patient then underwent a biopsy of the clinically uninvolved buccal mucosae. Results: Pathology of the buccal mucosae showed a positive direct immunofluorescence study. IgG showed a 2 to 3+ linear staining at the basement membrane zone. IgM was negative. IgA was negative. C3 showed a 1+ linear staining at the basement membrane zone. Fibrinogen was negative. Conclusion: Cicatricial pemphigoid is a chronic and often hard to diagnose disease. We report a case of using pathologic diagnosis of uninvolved oral mucosae to diagnose this patient. Commercial support: None identified.
P1700 Post-traumatic fingertip ulcer: A unique presentation of cutaneous diphtheria Shannon Humphrey, MD, Department of Dermatology and Skin Science, University of British Columbia, Vancouver, British Columbia, Canada; Marc Romney, MD, Clinical Assistant Professor, Department of Pathology & Laboratory Medicine, University of British Columbia, Vancouver, British Columbia, Canada; Richard I. Crawford, MD, Clinical Professor, Department of Dermatology and Skin Science, University of British Columbia, Vancouver, British Columbia, Canada; Nicole Hallgren, MD, Division of Plastic Surgery, University of British Columbia, Vancouver, British Columbia, Canada Background: Cutaneous diphtheria is a bacterial infection characterized by chronic ulcers. It is endemic in certain tropical and developing regions and rare in developed countries. In Vancouver, Canada, a non-toxigenic strain of Corynebacterium diphtheriae is known to circulate amongst the city’s downtown urban poor population. Case: A 45-year-old male presented with a right index fingertip ulcer. This developed subsequent to trauma sustained approximately 2 weeks earlier, and was associated with progressive pain, swelling, and erythema. Past medical history was significant for AIDS, with a recent CD4 count of 40 cells/mm3, and hepatitis C. He had been fully immunized as a child. The patient was homeless and had a lengthy forensic history. Clinical examination revealed a 1-cm ragged ulcer of the fingertip with an adherent yellow-green crust. The digit was diffusely swollen and erythematous. The flexor tendon sheath was non-tender and range of motion was intact. Radiographs showed no significant abnormality. The ulcer was debrided under local anesthesia. A grey-green gelatinous material was extracted from the ulcer. The patient was admitted to hospital for intravenous antibiotics and wound care. A tetanus and diphtheria immunization was administered. The patient left the hospital against medical advice within 24 hours. Wound culture isolated non-toxigenic C diphtheriae, Staphylococcus aureus, and b-hemolytic streptococci. Discussion: Primary cutaneous diphtheria is characterized by chronic, non-healing punched out ulcers with a firm border and a leathery grey membrane. The ulcers typically present on the lower extremities. There are no cases reporting cutaneous diphtheria of the fingertip or in the post-traumatic setting. Secondary infection with C diphtheriae can occur in preexisting skin lesions causing eczematous, impetiginous, and vesicular eruptions. Cutaneous diphtheria is rarely associated with signs of toxicity, as most strains are non-toxigenic and skin lesions absorb toxin slowly. Treatment of non-toxigenic cutaneous diphtheria consists of erythromycin 2 g/day orally or penicillin 2 to 4 million units IM/IV daily. Additional antibiotic coverage may be required for polymicrobial infection. Cutaneous diphtheria should be included in the differential diagnosis of non-healing skin ulcers in areas where C diphtheriae is endemic. We report a case of cutaneous diphtheria in a posttraumatic fingertip ulcer, which is a unique presentation of a rare infection. Commercial support: None identified.
P1621 The polymorphic nature of paraneoplastic pemphigus: A case report Cortney Vest, MD, Mayo Clinic, Rochester, MN, United States; Rochelle Torgerson, MD, PhD, Mayo Clinic, Rochester, MN, Alison Bruce, MBChB, Mayo Clinic, Rochester, MN Introduction: Paraneoplastic pemphigus (PNP) is a rare autoimmune mucocutaneous disease frequently associated with underlying neoplasms. It has a polymorphic nature both clinically and histologically, which can lead to difficulty in making this diagnosis. We describe a young healthy patient, with no known history of malignancy, who developed painful oral ulcerations. Previous outside workup was inconclusive, and a diagnosis was not reached despite biopsies and direct immunofluorescence (DIF) studies. Our work-up eventually led to a diagnosis of PNP, acknowledging that this was not initially included in the differential diagnosis. Case report: A healthy 36-year-old female presented with a 5-month history of painful and extensive oral ulcerations without cutaneous lesions. Prior to presentation, the patient was evaluated by several physicians and outside biopsies for H&E and DIF were unremarkable. A formal diagnosis was not established. Histopathology of an oral ulcer revealed suprabasilar intraepithelial acantholysis, and DIF of this specimen was negative. Esophageal endoscopy was performed. During the biopsy procedure large portions of the esophageal mucosa sloughed from the underlying submucosa. Further testing using ELISA-based techniques revealed elevated levels of desmoglein 3. Indirect immunofluorescence (IIF) revealed bound antibodies to rat bladder, establishing a diagnosis of PNP. Discussion: The diagnosis of PNP can be straightforward when a patient has a known neoplasm and the clinical picture is characteristic. However, PNP should be considered in the differential diagnosis when a patient presents with extensive oral ulceration and the clinical picture, histopathology, and DIF are not pathognomonic for a specific diagnosis. This case demonstrates this point and reinforces the importance of repeated biopsies, ELISA-based desmoglein antibody studies, and IIF when there is clinical suspicion for pemphigus vulgaris or PNP. This should be considered even in light of previously negative biopsies or a negative DIF study, as this patient illustrates. The importance of including PNP in the differential diagnosis becomes particularly evident in cases like this, as up to one-third of patients with PNP may not have a known malignancy at the time of presentation. Despite diagnosis and treatment of an occult malignancy, PNP has a poor prognosis. This is becase of the refractory nature of the severe stomatitis and from the myriad of systemic complications associated with this disease. Commercial support: None identified.
AB120
J AM ACAD DERMATOL
P1701 Screening outcomes for latent tuberculosis in worldwide adalimumab clinical trials John Perez, MD, Abbott Laboratories, Abbott Park, IL, United States; Hartmut Kupper, MD, Abbott Laboratories, Ludwigshafen, Germany; Martin Okun, MD, PhD, Abbott Laboratories, Abbott Park, IL, United States Objective: To assess the incidence of TB cases in adalimumab clinical trials and the effectiveness of isoniazid (INH) and other prophylaxis in preventing reactivation in high-risk patients. Methods: Data from patients in adalimumab trials were reviewed through November 2005. TB rates for rheumatoid arthritis (RA), ankylosing spondylitis (AS), Crohn’s disease, psoriatic arthritis (PsA), and psoriasis (Ps) were calculated for the periods before screening (primarily phase I) and after screening. Screening included clinical interviews, PPD tests (PPD+ defined by local/country-specific guidelines), and chest radiographs (most patients). INH or other prophylaxis was given for PPD+ and LTBreactivation high-risk patients (investigator identified). Results: Through November 31, 2005, 14563 patients (17870 patient-years [PYs] of exposure) were treated with adalimumab in clinical trials (8397 PYs [NA] and 9161 PYs [Europe]). Before screening, there were 8 TB cases in 534 PYs (0.015/PY). None of these patients received prophylaxis. After screening there were 46 TB cases in 17336 PYs (0.0027/PY). Six were in NA (0.00047/PY), and 29 were in Europe (0.0032/PY). No patients who received adalimumab for Ps, PsA, or AS developed TB at this cutoff. Median time to TB development (in days) was 232 (range: 29-1636). There were 30/54 (56%) culture-confirmed cases, and 33/54 (61%) extrapulmonary disease cases. The ratio of TB prior to screening to after screening represents an 82% reduction in TB development rate. In a subanalysis of 6610 European patients screened uniformly, 12% and 16% were classified as PPD+ by $ 10-mm and 5-mm induration cutoffs. A total of 835 high-risk patients were identified (most were PPD+) and received INH prior to the study drug. Five patients (1%) developed TB despite INH prophylaxis. Conclusions: TB screening resulted in substantial reduction in a LTB reactivation rate. TB rates were approximately 7-fold lower in NA than in Europe. Patients identified as high-risk for TB, and given prophylaxis prior to adalimumab treatment, rarely had LTB reactivation. Before the initiation of any TNF antagonist, all patients should be screened for LTB. 100% supported by Abbott.
FEBRUARY 2007
P1620 Biopsy proven cicatricial pemphigoid from uninvolved oral mucosae Laura Ganger, MD, Henry Ford Hospital Department of Dermatology, Detroit, MI, United States; Iltefat Hamzavi, MD, Henry Ford Hospital Department of Dermatology, Detroit, MI, United States Background and objective: Cicatricial pemphigoid is a chronic and often disabling disease. This condition tends to affect mostly the mucous membranes including the oral and conjunctival mucosae. Erosive desquamative gingivitis is a common oral presentation. Conjunctival involvement may result in blindness. Ocular involvement starts as a non-specific, chronic conjunctivitis, with burning, soreness, foreignbody sensation, or mucous production. Symblepharon formation is a common manifestation. Materials and methods: This is a case report of a patient with a 7-month history of grittiness and symblepharon of the left eye. He denied any involvement of the oral mucosae. The left conjunctivae was biopsied and was most likely consistent with cicatricial pemphigoid; however, the pathology was inconclusive. The patient then underwent a biopsy of the clinically uninvolved buccal mucosae. Results: Pathology of the buccal mucosae showed a positive direct immunofluorescence study. IgG showed a 2 to 3+ linear staining at the basement membrane zone. IgM was negative. IgA was negative. C3 showed a 1+ linear staining at the basement membrane zone. Fibrinogen was negative. Conclusion: Cicatricial pemphigoid is a chronic and often hard to diagnose disease. We report a case of using pathologic diagnosis of uninvolved oral mucosae to diagnose this patient. Commercial support: None identified.
P1700 Post-traumatic fingertip ulcer: A unique presentation of cutaneous diphtheria Shannon Humphrey, MD, Department of Dermatology and Skin Science, University of British Columbia, Vancouver, British Columbia, Canada; Marc Romney, MD, Clinical Assistant Professor, Department of Pathology & Laboratory Medicine, University of British Columbia, Vancouver, British Columbia, Canada; Richard I. Crawford, MD, Clinical Professor, Department of Dermatology and Skin Science, University of British Columbia, Vancouver, British Columbia, Canada; Nicole Hallgren, MD, Division of Plastic Surgery, University of British Columbia, Vancouver, British Columbia, Canada Background: Cutaneous diphtheria is a bacterial infection characterized by chronic ulcers. It is endemic in certain tropical and developing regions and rare in developed countries. In Vancouver, Canada, a non-toxigenic strain of Corynebacterium diphtheriae is known to circulate amongst the city’s downtown urban poor population. Case: A 45-year-old male presented with a right index fingertip ulcer. This developed subsequent to trauma sustained approximately 2 weeks earlier, and was associated with progressive pain, swelling, and erythema. Past medical history was significant for AIDS, with a recent CD4 count of 40 cells/mm3, and hepatitis C. He had been fully immunized as a child. The patient was homeless and had a lengthy forensic history. Clinical examination revealed a 1-cm ragged ulcer of the fingertip with an adherent yellow-green crust. The digit was diffusely swollen and erythematous. The flexor tendon sheath was non-tender and range of motion was intact. Radiographs showed no significant abnormality. The ulcer was debrided under local anesthesia. A grey-green gelatinous material was extracted from the ulcer. The patient was admitted to hospital for intravenous antibiotics and wound care. A tetanus and diphtheria immunization was administered. The patient left the hospital against medical advice within 24 hours. Wound culture isolated non-toxigenic C diphtheriae, Staphylococcus aureus, and b-hemolytic streptococci. Discussion: Primary cutaneous diphtheria is characterized by chronic, non-healing punched out ulcers with a firm border and a leathery grey membrane. The ulcers typically present on the lower extremities. There are no cases reporting cutaneous diphtheria of the fingertip or in the post-traumatic setting. Secondary infection with C diphtheriae can occur in preexisting skin lesions causing eczematous, impetiginous, and vesicular eruptions. Cutaneous diphtheria is rarely associated with signs of toxicity, as most strains are non-toxigenic and skin lesions absorb toxin slowly. Treatment of non-toxigenic cutaneous diphtheria consists of erythromycin 2 g/day orally or penicillin 2 to 4 million units IM/IV daily. Additional antibiotic coverage may be required for polymicrobial infection. Cutaneous diphtheria should be included in the differential diagnosis of non-healing skin ulcers in areas where C diphtheriae is endemic. We report a case of cutaneous diphtheria in a posttraumatic fingertip ulcer, which is a unique presentation of a rare infection. Commercial support: None identified.
P1621 The polymorphic nature of paraneoplastic pemphigus: A case report Cortney Vest, MD, Mayo Clinic, Rochester, MN, United States; Rochelle Torgerson, MD, PhD, Mayo Clinic, Rochester, MN, Alison Bruce, MBChB, Mayo Clinic, Rochester, MN Introduction: Paraneoplastic pemphigus (PNP) is a rare autoimmune mucocutaneous disease frequently associated with underlying neoplasms. It has a polymorphic nature both clinically and histologically, which can lead to difficulty in making this diagnosis. We describe a young healthy patient, with no known history of malignancy, who developed painful oral ulcerations. Previous outside workup was inconclusive, and a diagnosis was not reached despite biopsies and direct immunofluorescence (DIF) studies. Our work-up eventually led to a diagnosis of PNP, acknowledging that this was not initially included in the differential diagnosis. Case report: A healthy 36-year-old female presented with a 5-month history of painful and extensive oral ulcerations without cutaneous lesions. Prior to presentation, the patient was evaluated by several physicians and outside biopsies for H&E and DIF were unremarkable. A formal diagnosis was not established. Histopathology of an oral ulcer revealed suprabasilar intraepithelial acantholysis, and DIF of this specimen was negative. Esophageal endoscopy was performed. During the biopsy procedure large portions of the esophageal mucosa sloughed from the underlying submucosa. Further testing using ELISA-based techniques revealed elevated levels of desmoglein 3. Indirect immunofluorescence (IIF) revealed bound antibodies to rat bladder, establishing a diagnosis of PNP. Discussion: The diagnosis of PNP can be straightforward when a patient has a known neoplasm and the clinical picture is characteristic. However, PNP should be considered in the differential diagnosis when a patient presents with extensive oral ulceration and the clinical picture, histopathology, and DIF are not pathognomonic for a specific diagnosis. This case demonstrates this point and reinforces the importance of repeated biopsies, ELISA-based desmoglein antibody studies, and IIF when there is clinical suspicion for pemphigus vulgaris or PNP. This should be considered even in light of previously negative biopsies or a negative DIF study, as this patient illustrates. The importance of including PNP in the differential diagnosis becomes particularly evident in cases like this, as up to one-third of patients with PNP may not have a known malignancy at the time of presentation. Despite diagnosis and treatment of an occult malignancy, PNP has a poor prognosis. This is becase of the refractory nature of the severe stomatitis and from the myriad of systemic complications associated with this disease. Commercial support: None identified.
AB120
J AM ACAD DERMATOL
P1701 Screening outcomes for latent tuberculosis in worldwide adalimumab clinical trials John Perez, MD, Abbott Laboratories, Abbott Park, IL, United States; Hartmut Kupper, MD, Abbott Laboratories, Ludwigshafen, Germany; Martin Okun, MD, PhD, Abbott Laboratories, Abbott Park, IL, United States Objective: To assess the incidence of TB cases in adalimumab clinical trials and the effectiveness of isoniazid (INH) and other prophylaxis in preventing reactivation in high-risk patients. Methods: Data from patients in adalimumab trials were reviewed through November 2005. TB rates for rheumatoid arthritis (RA), ankylosing spondylitis (AS), Crohn’s disease, psoriatic arthritis (PsA), and psoriasis (Ps) were calculated for the periods before screening (primarily phase I) and after screening. Screening included clinical interviews, PPD tests (PPD+ defined by local/country-specific guidelines), and chest radiographs (most patients). INH or other prophylaxis was given for PPD+ and LTBreactivation high-risk patients (investigator identified). Results: Through November 31, 2005, 14563 patients (17870 patient-years [PYs] of exposure) were treated with adalimumab in clinical trials (8397 PYs [NA] and 9161 PYs [Europe]). Before screening, there were 8 TB cases in 534 PYs (0.015/PY). None of these patients received prophylaxis. After screening there were 46 TB cases in 17336 PYs (0.0027/PY). Six were in NA (0.00047/PY), and 29 were in Europe (0.0032/PY). No patients who received adalimumab for Ps, PsA, or AS developed TB at this cutoff. Median time to TB development (in days) was 232 (range: 29-1636). There were 30/54 (56%) culture-confirmed cases, and 33/54 (61%) extrapulmonary disease cases. The ratio of TB prior to screening to after screening represents an 82% reduction in TB development rate. In a subanalysis of 6610 European patients screened uniformly, 12% and 16% were classified as PPD+ by $ 10-mm and 5-mm induration cutoffs. A total of 835 high-risk patients were identified (most were PPD+) and received INH prior to the study drug. Five patients (1%) developed TB despite INH prophylaxis. Conclusions: TB screening resulted in substantial reduction in a LTB reactivation rate. TB rates were approximately 7-fold lower in NA than in Europe. Patients identified as high-risk for TB, and given prophylaxis prior to adalimumab treatment, rarely had LTB reactivation. Before the initiation of any TNF antagonist, all patients should be screened for LTB. 100% supported by Abbott.
FEBRUARY 2007