Background The clinical mucocutaneous manifestations of glucagonoma syndrome are recognized easily when they occur in the classic pattern of acral or periorificial lesions evolving in recurrent crops, with an annular and migratory distribution, in a patient with diabetes mellitus who has had recent weight loss and anemia. Not infrequently, noncharacteristic clinical and histopathologic features are observed and, in these cases, the diagnosis of pancreatic neoplasm may be delayed. Aim To review the clinical and histopathologic features of cutaneous manifestations of glucagonoma syndrome. Methods The clinicopathologic features of 13 patients (eight women) with widespread or localized cutaneous eruption as a manifestation of islet cell pancreatic carcinoma with marked glucagon secretion (glucagonoma) were reviewed. Results The definitive diagnosis of the cutaneous eruption was established at the time of diagnosis of the pancreatic neoplasm (three patients) or afterwards (10 patients). In nine patients, the mucocutaneous manifestations preceded the diagnosis of the pancreatic neoplasm by 1 month to 3 years (mean, 12 months). In only eight biopsy specimens were the histopathologic features considered to be suggestive or characteristic of necrolytic migratory erythema. Diffuse parakeratosis, that occasionally arose abruptly from normal epidermis, was observed in 12 biopsy specimens. By the time necrolytic migratory erythema was diagnosed, the pancreatic carcinoma had metastasized to the liver, regional lymph nodes, or bone in 12 patients. Conclusion Increased awareness of the polymorphic mucocutaneous and nonspecific histopathologic features of glucagonoma syndrome is needed to avoid unnecessary delay in the diagnosis of this syndrome.

OBJECTIVETo describe the clinical and laboratory findings in patients with pseudoporphyria.PATIENTS AND METHODSThis retrospective review identified 261 patients with either porphyrin metabolism abnormalities or pseudoporphyria who were seen at the Mayo Clinic in Rochester, Minn, between 1992 and 1996. All patients with documented porphyria cutanea tarda (PCT), noncutaneous porphyrias, or variegate porphyria were excluded.RESULTSTwenty patients had active cutaneous lesions resembling PCT with no diagnostic laboratory abnormalities. The major presenting clinical features were blistering in 19 patients (95%), scarring in 14 (70%), photosensitivity in 13 (65%), skin fragility in 13 (65%), and milia in 8 (40%). Histologically, of 17 patients tested, 12 (71%) had classic findings of subepidermal separation with festooning of dermal papillae. None of the 11 patients tested had hepatitis B or C. In all 20 patients, porphyrin profiles were nondiagnostic. Of 16 patients for whom follow-up was available, 11 reported persistent symptoms for a mean of 2.5 years after evaluation. Five patients were free of symptoms 1 week to 6 months after discontinuation of the presumed offending agent.CONCLUSIONPseudoporphyria mimics the cutaneous symptoms of PCT in the setting of normal or near-normal porphyrin levels in the serum, urine, or stool. Despite efforts to discontinue an offending medication, symptoms may persist indefinitely.

Scleromyxedema is a disorder characterized by a typical rash due to the accumulation of mucin in the dermis. It is always associated with a monoclonal protein in the serum and can have a wide variety of systemic manifestations. We describe a 40-year-old woman who had scleromyxedema associated with a monoclonal G lambda protein. Severe systemic symptoms included fatigue, esophageal dysmotility, and myopathy. Symptoms resolved completely with oral prednisone therapy, and she remained in clinical remission 24 months after use of prednisone was discontinued. Scleromyxedema is commonly treated with alkylating agents, which have been associated with pronounced morbidity and mortality. We suggest that oral corticosteroid therapy may be a reasonable initial choice for treating this disease and that alkylating agents be reserved for corticosteroid-refractory disease.

To provide an overview of the clinicopathologic correlation of the various types of malignant melanoma, we describe and illustrate the four major types of these tumors and discuss the concept of microstaging for the prognostic evaluation of melanoma. The four major types of malignant melanoma are lentigo maligna melanoma, acral lentiginous melanoma, superficial spreading melanoma, and nodular melanoma. Lentigo maligna melanoma has irregular margins and usually occurs on sunlight-exposed skin in elderly patients. Acral lentiginous melanoma occurs on the hands and feet; it often demonstrates massive invasion when the vertical growth phase occurs. Among Caucasians, superficial spreading melanoma, which affects the trunk and extremities, is the most common malignant melanoma. These lesions are often variegated in color. Nodular melanomas are deeply pigmented and enlarge rapidly. For microstaging of malignant melanoma, determining Clark's level of tumor invasion or Breslow's thickness (from the top of the granular cell layer of the epidermis to the deepest extension of the tumor) is useful for assessment of prognosis. Establishing a definite diagnosis of malignant melanoma is feasible through clinicopathologic correlation. Microscopic measurement of the deepest levels of melanoma involvement in the skin provides a useful indication of the associated prognosis.

We report two cases of microcystic adnexal carcinoma showing extensive sebaceous differentiation. Multiple cellular nests and strands within a moderately sclerotic stroma involving the full thickness of the dermis were observed. Clusters of basaloid cells with extensive sebaceous differentiation were present. Foci of sebaceous ductal differentiation were observed in the more superficial areas. Neither strikingly atypical cells nor mitotic figures were present. Perineural invasion was present in the deep areas of both tumors. Clinically, the lesions were solitary whitish-pink papules with a central dell on the faces of 2 men (aged 78 and 73 years old). We propose a relationship between these tumors and other cytologically bland but locally aggressive adnexal carcinomas. Sebaceous differentiation itself in a poorly circumscribed neoplasm does not indicate conventional extraocular sebaceous carcinoma. We propose a simple classification of locally aggressive adnexal carcinomas that takes into account the full range of adnexal differentiation that can occur in such lesions.

Background: Allergic granulomatosis of Churg-Strauss (Churg-Strauss syndrome) is a distinct clinical disease of multisystem vasculitis.Objective: We characterize the clinical and histologic features of cutaneous findings in Churg-Strauss syndrome.Methods: All patients with Churg-Strauss syndrome seen between 1976 and 1995 were retrospectively reviewed.Results: Ninety patients with the diagnosis of Churg-Strauss syndrome were identified; 36 (40%) had cutaneous findings. Five patients (6%) had skin lesions as the initial manifestation. The most frequent cutaneous findings were purpura and petechiae on the lower extremities and cutaneous nodules and papules on the elbows. in 37 biopsy specimens from 29 patients, the most common findings were extravascular necrotizing granuloma (15 specimens) and leukocytoclastic vasculitis (16 specimens).Conclusion: Cutaneous lesions in Churg-Strauss syndrome are common. Their characteristic clinical and histologic pattern may help establish the diagnosis.

OBJECTIVETo determine the incidence, prevalence, survival rates, clinical manifestations, and longterm outcome of patients with morphea (localized scleroderma) and its subtypes over a 33 year period in Olmsted County, Minnesota.METHODSWe used the unique data resources of the Rochester Epidemiology Project to review all Olmsted County medical records with any potential diagnosis consistent with morphea (including plaque, generalized, bullous, linear, and deep entities) from 1960 through 1993.RESULTSWe screened 1030 medical records and identified 82 (59 female; 23 male) cases of morphea first diagnosed between 1960 and 1993. All cases were followed until death or migration from Olmsted County, a total of 754 person-years of observation. The annual age and sex adjusted incidence rate per 100,000 population was 2.7 (95% confidence interval 2.1, 3.3). The incidence rate increased significantly over the 33 years (p = 0.0037) on an average of 3.6% per year. The prevalence (estimated using cumulative incidence) at 80 years of age was about 2/1000. 50% of the patients had a cutaneous softening or evidence of disease resolution by 3.8 years' duration. The shortest active disease duration was found in the plaque group (50% resolution or skin softening by 2.7 years) compared to 5.5 years in the deep group. Arthralgias, synovitis, uveitis, and joint contractures were more frequent in the linear and deep categories. Although 9 patients (11%) developed some disease related disability over the followup period, this was common (44%) in the deep group. No case of morphea developed severe internal organ involvement and none progressed to systemic sclerosis. The survival rate was not significantly different from the general population (p = 0.409).CONCLUSIONMorphea, and its subtypes, are more common than previously recognized, and can lead to important disability.

We appreciate the interest of Dr. Miller and colleagues. Our review article has 151 references. Obviously, we could review only the main points in each reference and not critique each one of them. We agree with Dr. Miller and associates that radiotherapy is most beneficial for painful or cosmetically troublesome Kaposi's sarcoma and that complications with use of radiation therapy for oral Kaposi's sarcoma are severe. Extreme caution should be exercised when irradiation is used for visceral organs in patients with the human immunodeficiency virus (HIV). The brief report by Drs. Narasimhan and Hitti was interesting. As we demonstrated in our review article, multiple atypical or exaggerated symptoms can occur in patients with HIV infection. Because emergency tracheostomy provides immediate relief for these patients, we appreciate the authors sharing their experience.

A 35-year-old female day-care worker sought medical assistance because of a history of small tender nodules developing on the left lateral buttock area. These nodules had appeared 4 days earlier, after the patient had been working in her garden; therefore, they were ascribed to a possible insect bite. The skin lesions began as red, warm, tender, and indurated areas (Fig. 1) associated, 4 to 5 days later, with spontaneous drainage of serosanguineous fluid. For the next few months, multiple ulcerated lesions (up to 3 by 2 em) developed on the buttocks and thighs (Fig. 2). The lesions then stopped draining and healed, but subcutaneous atrophy and hyperpigmentation remained. A skin biopsy specimen obtained by her local physician revealed nonspecific chronic dermatitis. Topically applied corticosteroids seemed to exacerbate the lesions. During this time, she remained afebrile and had no chills, sweats, cough, arthralgia, fatigue, or dyspnea. During the 3 months before the patient was examined at our institution, several regimens of antibiotics and oral corticosteroid therapy yielded no appreciable improvement or cessation of recurrent ulcerations. 1.Which one of the following is the most likely dermatologic diagnosis at this point? a.Erythema nodosumb.Pyoderma gangrenosumc.Panniculitisd.Bacterial cellulitise.Cutaneous polyarteritis nodosaFig. 2Ulceration on thigh, with exudation of serosanguineous fluid.View Large Image Figure ViewerDownload (PPT) Eruption due to erythema nodosum can be associated with various disease processes, although it is not characterized by ulcerating lesions. Recurrence, as noted in this patient, is uncommon in erythema nodosum. Pyoderma gangrenosum, considered noninfectious in origin, clinically exhibits a painful nodule or pustule that ulcerates and drains a purulent exudate and has a necrotic base. In our patient, the lesions did not demonstrate the rapid expansion and ulceration that are characteristic of pyoderma gangrenosum. The appearance of single or multiple areas of tender or nontender nodules that ranged in size from 0.5 to 10 cm, with deep induration and eventual ulceration in addition to serosanguineous drainage, makes panniculitis most likely. Although the initial nodular phase of panniculitis can be mistaken for cellulitis, bacterial cellulitis is much less likely to ulcerate and does not have a serosanguineous exudate. This patient had received several courses of antibiotic therapy and should have responded favorably if the skin lesions were indeed caused by a bacterial infection. Cutaneous polyarteritis nodosa is a benign cutaneous variant of polyarteritis nodosa that manifests with tender erythematous papules or nodules associated with livedo reticularis. This patient did not have the pattern of livedo reticularis that is often seen in cutaneous polyarteritis nodosa.1Su WPD Diseases of the subcutaneous tissue.in: Moschella SL Hurley HJ 3rd ed. Dermatology. Vol 2. Saunders, Philadelphia1992: 1312-1332Google Scholar The patient was referred to our institution for further evaluation of the refractory skin lesions. On questioning, she had no history of systemic illness, no known irritant chemical exposure, and no history of trauma. She was a nonsmoker and had no history of alcohol or drug abuse. The family history was unremarkable. Physical examination showed multiple indurated, subcutaneous plaques (up to 3 by 2 cm) on the left buttock. A large ulcer (approximately 8 by 4 cm) noted on the anterior aspect of the right thigh had an irregular and slightly erythematous border and an irregular exudative base (Fig. 2). Another ulcer on the left anterior aspect of the thigh had a hemorrhagic central eschar. Several healed ulcers were also noted on the thighs (Fig. 1). We were informed by the patient that the earlier, now healed, ulcers were identical to the new ulcers (depicted in the illustrations). Laboratory evaluation revealed normal complete blood cell count, electrolytes, and liver enzymes and normal findings on urinalysis, chest roentgenography, and electrocardiography. The erythrocyte sedimentation rate was mildly increased at 35 mm in 1 hour (normal, 0 to 29). The anti-double-stranded DNA antibody was borderline at 111 U (negative, less than 70; borderline, 70 to 200; and positive, more than 200). On the basis of information available thus far, our clinical impression was that the skin lesions represented a type of panniculitis, the cause of which was unclear. 2.On the basis of the information provided, which one of the following factors is most likely to have caused the skin lesions? a.Connective tissue diseaseb.Systemic infectionc.Pancreatitisd.Traumae.Deficiency of α1-antitrypsin Panniculitis associated with systemic disease may involve connective tissue diseases. Lupus erythematosus is probably the most common, and 2 to 3% of patients manifest nodular fat necrosis. Panniculitis is more commonly associated with discoid lupus erythematosus than systemic lupus erythematosus. Although our patient had borderline anti-double-stranded DNA antibody, she did not have other clinical signs of lupus erythematosus. Infectious causes of panniculitis, including Cryptococcus, Candida, Histoplasma, staphyiococci, streptococci, and Pseudomonas, are usually associated with an immunocompromised state. Our patient's clinical and laboratory findings do not suggest an immunocompromised condition. Furthermore, she had no clinical features suggestive of an underlying systemic infection. Both acute and chronic cases of pancreatitis are known to be associated with subcutaneous fat necrosis, but these conditions are unlikely in our patient, who had no gastrointestinal complaints, no history of alcohol abuse, and normal results of a complete blood cell count and liver function tests. Because our patient did not have a history of physical injury to the areas of ulceration, traumatic panniculitis is unlikely. Panniculitis can be a manifestation of deficiency of α1-antitrypsin. Biopsy specimens of skin lesions and immunologic assay to estimate the level of α1-antitrypsin are needed for confirmation.2Bondi EE Lazarus GS Disorders of subcutaneous tissue.in: Fitzpatrick TB Eisen AZ Wolff K Freedberg IM Austen KF 4th ed. Dermatology in General Medicine. Vol 1. McGraw-Hill, New York1993: 1329-1344Google Scholar, 3Su WPD Smith KC Pittelkow MR Winkelmann RK α1-Antitrypsin deficiency panniculitis: a histopathologic and immunopathologic study of four cases.Am J Dermatopathol. 1987; 9: 483-490Crossref PubMed Scopus (45) Google Scholar These factors suggested the possibility of α1-antitrypsin deficiency. A skin biopsy specimen of the right thigh revealed acute dermal and subcutaneous inflammation in conjunction with a prominent neutrophilic and histiocytic infiltrate as well as necrosis. These features were consistent with a deficiency of α1-antitrypsin. Other histopathologic findings consistent with α1-antitrypsin deficiency, seen in our patient and described in similar patients, include large areas of normal fat tissue adjacent to necrotic panniculitis, a severe degree of necrosis and infiltration with neutrophils splaying the collagen bundles of the reticular dermis, secondary leukocytoclastic and lymphocytic vasculitis, and focal collection of histiocytes and macrophages.4Hendrick SJ Silverman AK Solomon AR Headington JT α1-Antitrypsin deficiency associated with panniculitis.J Am Acad Dermatol. 1988; 18: 684-692Abstract Full Text PDF PubMed Scopus (61) Google Scholar The serum α1-antitrypsin level in our patient was 20 mg/dL (normal, 126 to 226), and her α1-antitrypsin phenotype was PiZZ. Our patient was thus diagnosed to have the dermatologic manifestation of α1-antitrypsin deficiency—namely, panniculitis. 3.Which one of the following disorders is unlikely to occur in patients with the hereditary deficiency of protein documented in our patient? a.Panlobular emphysemab.Macular degenerationc.Hepatic cirrhosisd.Glomerulonephritise.Rheumatoid arthritis PiZZ variety of α1-antitrypsin deficiency is most notably associated with panlobular emphysema. Emphysema does not develop, however, in all persons with PiZZ variety of α1-antitrypsin deficiency. Our patient had no symptoms or signs of emphysema. Macular degeneration is not a known manifestation of this disorder. Evidence for increased susceptibility to anterior uveitis remains unclear.5Cox DW α1-Antitrypsin: a guardian of vascular tissue [editorial].Mayo Clin Proc. 1994; 69: 1123-1124Abstract Full Text Full Text PDF PubMed Scopus (26) Google Scholar Although the mechanism has not yet been determined, α1-antitrypsin deficiency in adults is associated with an increased risk of cirrhosis and sometimes necessitates liver transplantation. The abnormal Z protein has a tendency to self-aggregate and thereby produce molecular complexes or inclusions, which accumulate in the liver.5Cox DW α1-Antitrypsin: a guardian of vascular tissue [editorial].Mayo Clin Proc. 1994; 69: 1123-1124Abstract Full Text Full Text PDF PubMed Scopus (26) Google Scholar Liver biopsy specimens in subjects (even in the absence of liver disease clinically or by laboratory criteria) with deficiency of α1-antitrypsin may reveal hepatocytes filled with periodic acid-Schiff-positive α1-antitrypsin. The role of α1-antitrypsin deficiency in the development of nonspecific glomerular disease is not understood but has been described in case reports.6Stauber RE Horina JH Trauner M Krejs GJ Ratschek M Klimpfinger M Glomerulonephritis as late manifestation of severe α1-antitrypsin deficiency.Clin Investigator. 1994; 72: 404-408PubMed Google Scholar Severe rheumatoid arthritis has been associated with α1-antitrypsin deficiency, particularly among heterozygote female patients with a suspected increased risk for progression to severe destructive joint disease.7Cox DW Huber O Association of severe rheumatoid arthritis with heterozygosity for α1-antitrypsin deficiency.Clin Genet. 1980; 17: 153-160Crossref PubMed Scopus (32) Google Scholar As noted previously, no manifestation of α1-antitrypsin deficiency other than panniculitis was exhibited in our patient. She was a nonsmoker and had normal results of pulmonary function tests. 4.Which one of the following is the best treatment for the dermatologic disease in this patient? a.Dapsoneb.Long-term antibiotic therapyc.A corticosteroidd.Danazole.Cyclophosphamide Dapsone, a sulfone drug, is thought to be effective in stabilizing the lysosomal enzymes of neutrophils in addition to augmenting antioxidant preservation in a setting of already limited α1-antitrypsin. It is the treatment of choice for panniculitis associated with α1-antitrypsin deficiency. Antibiotic therapy is ineffective in treating panniculitis, unless a superimposed infection is present. Corticosteroids are occasionally used for acute fulminant exacerbations but are variable in efficacy and may not prevent progressive deterioration.4Hendrick SJ Silverman AK Solomon AR Headington JT α1-Antitrypsin deficiency associated with panniculitis.J Am Acad Dermatol. 1988; 18: 684-692Abstract Full Text PDF PubMed Scopus (61) Google Scholar Our patient had no improvement in her condition despite several courses of corticosteroid therapy; indeed, she believed that topical application of a corticosteroid exacerbated the lesions. Danazol, a synthetic androgen derivative, apparently improves the hepatic export of α1-antitrypsin in PiZZ phenotypes, but its use has not been correlated with decreased lesions of panniculitis.8Wewers MD Gadek JE Keogh BA Fells GA Crystal RG Evaluation of danazol therapy for patients with PiZZ α1-antitrypsin deficiency.Am Rev Respir Dis. 1986; 134: 476-480PubMed Google Scholar Cyclophosphamide is ineffective in treating α1-antitrypsin-associated panniculitis.1Su WPD Diseases of the subcutaneous tissue.in: Moschella SL Hurley HJ 3rd ed. Dermatology. Vol 2. Saunders, Philadelphia1992: 1312-1332Google Scholar 5.Which one of the following statements, as it relates to patients with the inherited disorder and the associated dermatologic complication described in our patient, is not correct? a.Cigarette smoking may lead to panlobutar emphysemab.Blood-relatives should be tested for deficiency of the protein noted in this patientc.Pregnancy is contraindicatedd.Trauma to the skin and intramuscular injections should be avoidede.In this condition, skin lesions are a chronic relapsing problem Although panlobular emphysema can develop in the absence of cigarette smoking in patients with α1-antitrypsin deficiency, the risk is substantially increased in smokers with this condition. Patients with this disorder should also be advised to avoid alcohol and other hepatotoxins that may predispose to the associated liver disease. Relatives of the patient should have α1-antitrypsin levels and phenotypes tested. This information will be important for genetic counseling. Pregnancy is not contraindicated in patients with α1-antitrypsin deficiency. Reported cases have suggested watchful consideration during labor in patients with emphysema. The Valsalva maneuver during vaginal delivery may be associated with an increased risk of spontaneous pneumo-thorax in such patients.9Atkinson AR Pregnancy and α1-antitrypsin deficiency.Postgrad Med J. 1987; 63: 817-820Crossref PubMed Scopus (11) Google Scholar Direct trauma often precedes the development of panniculitis as a complication of α1-antitrypsin deficiency. Therefore, these patients should be advised to avoid trauma to the skin and intramuscular injections. Patients with this disorder should be informed that α1-antitrypsin-associated panniculitis is a chronic relapsing condition that can be controlled with appropriate therapy. In our patient, initiation of dapsone therapy, 150 mg orally once a day, yielded good resolution of the existing lesions and no development of new lesions. Initially, as the dosage of dapsone was tapered to 25 mg/day, recurrent skin lesions developed, and the dosage had to be increased to 150 mg daily to curb this activity. The patient is now well maintained on dapsone, 50 mg weekly, without recurrence of panniculitis, and the previous lesions have remained healed. The polypeptide glycoprotein α1-antitrypsin, synthesized in the liver, is the most abundant protease inhibitor in human plasma. The inhibitor property is important in protecting tissue from damage inflicted by various proteases, particularly ncutrophil elastase. The phenotypic expression of the recessively inherited deficiency of α1-antitrypsin may vary. Ninety-five percent of the US population exhibit the normal protease inhibitor PiMM phenotype. Phenotype PiZZ, expressed in approximately 1 in 2,500 Caucasians in the United States, results in an α1-antitrypsin variant that differs from the M protein by a single amino acid substitution (lysine for glutamic acid). This single substitution results in a considerable alteration of the enzyme, inhibition of release of α-antitrypsin from hepatocytes, and decreased serum levels of α1-antitrypsin in patients with the ZZ phenotype. Of the various phenotypes, the homozygote or PiZZ has among the lowest serum levels of α1-antitrypsin and is strongly associated with panniculitis.10Smith KC Pittelkow MR Su WPD Panniculitis associated with severe α1-antitrypsin deficiency: treatment and review of the literature.Arch Dermatol. 1987; 123: 1655-1661Crossref PubMed Scopus (85) Google Scholar Our patient's father, mother, and brother seemed to be heterozygotes with α1-antitrypsin levels of 84, 100, and 201 mg/dL, respectively. The lesions of panniculitis associated with α1-antitrypsin deficiency begin as tender, crythematous, indurated, subcutaneous nodules that may be widely disseminated on the torso or extremities. This panniculitis is a chronic and relapsing condition. New lesions appear as old lesions resolve, as exemplified in our patient. The release of elastase and collagenase from neutrophil granules is uninhibited in the presence of α1-antitrypsin deficiency, and the result is destruction of collagen and elastic fibers. Why panniculitis develops in only a few patients with α1-antitrypsin deficiency is unknown.4Hendrick SJ Silverman AK Solomon AR Headington JT α1-Antitrypsin deficiency associated with panniculitis.J Am Acad Dermatol. 1988; 18: 684-692Abstract Full Text PDF PubMed Scopus (61) Google Scholar, 10Smith KC Pittelkow MR Su WPD Panniculitis associated with severe α1-antitrypsin deficiency: treatment and review of the literature.Arch Dermatol. 1987; 123: 1655-1661Crossref PubMed Scopus (85) Google Scholar Panlobular emphysema is perhaps the most commonly known complication in patients with α1-antitrypsin deficiency. The neutrophil elastase is an important factor in the host defense mechanism of the lung. It also is the only inflammatory cell product shown to produce emphysema in animals. In the case of severe deficiency of the principal protease inhibitor, α1-antitrypsin, the destructive potential is unabated. This process is further exacerbated by cigarette smoking, which not only suppresses the α1-antitrypsin activity but also stimulates the production of neutrophil chemotactic factors in the lung. This process is suspected to cause the migration of more potentially destructive neutrophils into the lung. Emphysema associated with a:-antitrypsin manifests clinically between 30 and 40 years of age in smokers and between 40 and 50 years of age in nonsmokers. Even in the absence of cigarette smoking, homozygotes with less than 10% of normal antitrypsin levels have an estimated 70 to 80% chance of developing emphysema. Other distinguishing factors include the predominance of emphysematous changes in the lower lung zones on a chest roentgenogram and the panlobular form of emphysema histologically. The lower-zone predominance of lung involvement is attributable to greater blood flow to that region of the lung.11Buist AS α1-Antitrypsin deficiency-diagnosis, treatment, and control: identification of patients.Lung. 1990; 168: 543-551Crossref PubMed Scopus (14) Google Scholar The imbalance in protease and antiprotease activity, as seen in α1-antitrypsin deficiency, is also thought to contribute to arterial wall disease and result in aneurysm formation, dissection, and fibromuscular dysplasia. A retrospective study of autopsy material at the Mayo Clinic found the incidence of fibromuscular dysplasia to be 33% in patients with α1-antitrypsin deficiency versus 0.3% in patients not known to have α1-antitrypsin deficiency.12Schievink WI Bjõrnsson J Parisi JE Prakash UBS Arterial fibromuscular dysplasia associated with severe α1-antitrypsin deficiency.Mayo Clin Proc. 1994; 69: 1040-1043Abstract Full Text Full Text PDF PubMed Scopus (54) Google Scholar In addition to patients with abdominal aortic aneurysms being found to have decreased circulating amounts of α1-antitrypsin, patients with α1-antitrypsin deficiency represent a substantial proportion of those with abdominal aortic aneurysm.5Cox DW α1-Antitrypsin: a guardian of vascular tissue [editorial].Mayo Clin Proc. 1994; 69: 1123-1124Abstract Full Text Full Text PDF PubMed Scopus (26) Google Scholar Because cigarette smoking is the major environmental risk factor for abdominal aortic aneurysm and is shown to decrease the biologic effect of α1-antitrypsin, the combination of cigarette smoking and α1-antitrypsin deficiency may be an important contributor to arteriopathy. Although the treatment options are limited in patients with emphysema caused by the deficiency of α1-antitrypsin, the most important intervention is to avoid cigarette smoking. Replacement of the deficient protein is a logical consideration for therapy in this condition. Weekly intravenous infusions of random donor-derived human α1-antitrypsin have been shown to be effective in controlling panniculitis.10Smith KC Pittelkow MR Su WPD Panniculitis associated with severe α1-antitrypsin deficiency: treatment and review of the literature.Arch Dermatol. 1987; 123: 1655-1661Crossref PubMed Scopus (85) Google Scholar This therapeutic option was not available to our patient at the time of her evaluations at our institution. Whether this route or the aerosolized administration will be effective in treating emphysema and other complications of this condition remains uncertain.10Smith KC Pittelkow MR Su WPD Panniculitis associated with severe α1-antitrypsin deficiency: treatment and review of the literature.Arch Dermatol. 1987; 123: 1655-1661Crossref PubMed Scopus (85) Google Scholar

International Journal of DermatologyVolume 35, Issue 4 p. 240-248 CRYOGLOBULINEMIA: RECENT FINDINGS IN CUTANEOUS AND EXTRACUTANEOUS MANIFESTATIONS MARK D.P. DAVIS M.B., M.R.C.P.I., MARK D.P. DAVIS M.B., M.R.C.P.I. Department of Dermatology, Mayo Clinic and Mayo Foundation, Rochester, Minnesota.Search for more papers by this authorW.P. DANIEL SU M.D., Corresponding Author W.P. DANIEL SU M.D. Department of Dermatology, Mayo Clinic and Mayo Foundation, Rochester, Minnesota.W.P. Daniel Su, M.D., c/o Section of Publications, Mayo Clinic, 200 First Street SW, Rochester, MN 55905.Search for more papers by this author MARK D.P. DAVIS M.B., M.R.C.P.I., MARK D.P. DAVIS M.B., M.R.C.P.I. Department of Dermatology, Mayo Clinic and Mayo Foundation, Rochester, Minnesota.Search for more papers by this authorW.P. DANIEL SU M.D., Corresponding Author W.P. DANIEL SU M.D. Department of Dermatology, Mayo Clinic and Mayo Foundation, Rochester, Minnesota.W.P. Daniel Su, M.D., c/o Section of Publications, Mayo Clinic, 200 First Street SW, Rochester, MN 55905.Search for more papers by this author First published: April 1996 https://doi.org/10.1111/j.1365-4362.1996.tb02995.xCitations: 17AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat Citing Literature Volume35, Issue4April 1996Pages 240-248 RelatedInformation

Two cases of solitary tumors showing well-demarcated hypocellular, dermal fibrocollagenous proliferations are reported. The lesions were composed of hyalinized eosinophilic collagen bundles arranged in the characteristic interwoven pattern with prominent clefts, as described in sclerotic fibroma of the skin. This pattern, although predominant, was not uniform. Some areas showed a more cellular pattern with histopathologic features suggestive of dermatofibroma. In those areas, multiple spindle-shaped cells and occasional multinucleated cells were observed. The collagen bundles did not adopt a whorled pattern, and the overlying epidermis showed mild acanthosis and elongation of the rete ridges. The sclerotic changes were present mainly at the periphery and in the deep areas of the tumor. Our observations confirm the possibility that solitary sclerotic fibroma of the skin may represent, at least in some instances, the later and sclerotic stage of other more cellular neoplasms (specifically dermatofibromas) rather than an individualized neoplasm, as has been recently proposed.

A full-term infant with junctional epidermolysis bullosa (JEB) is described. The distribution and morphologic characteristics of generalized blistering in areas of pressure in conjunction with perioral and perinasal granulation tissue suggested the diagnosis of generalized gravis (Herlitz) JEB. The family history was consistent with autosomal recessive inheritance. Electron microscopy demonstrated a subepidermal cleft arising in the lamina lucida with hemidesmosomal hypoplasia, findings consistent with gravis JEB. Immunofluorescent antigenic mapping localized laminin and type IV collagen exclusively to the blister base and weak reactivity of bullous pemphigold antigen to both the roof and the base. Type VII collagen (LH 7:2 epitope) was detected solely at the base of the cleavage plane, and abnormal staining of laminin 5 (kalinin, GB3, nicein) and 19-DEJ-1 antigen was observed. The patient died of sepsis at age 3 months. DNA extracted from cultured keratinocytes for molecular genetic analysis demonstrated a mutation with the LAMB3 gene encoding the beta 3 chain of laminin 5. We present the clinical and laboratory findings and briefly review recent advances in the diagnosis and management of JEB.

Clinicopathologic correlation of cutaneous biopsy specimens demonstrating typical lipomembranous fat necrosis was performed. Material from 732 biopsies of various subcutaneous inflammatory disorders seen at our institution in the past 5 years was screened for typical lipomembranous (membranocystic) changes in the panniculus, and 39 specimens from 38 patients with these changes were identified. The most common clinical context in which this condition was observed was in chronic sclerotic plaques of the lower legs associated with venous insufficiency (37% of the total cases). All patients were women, and the majority were obese. Typical lipomembranous fat necrosis was also observed in eight cases (21%) of erythema nodosum, three (8%) of morphea or subcutaneous morphea (or both), two (5%) of lupus panniculitis, two (5%) of necrobiosis lipoidica, and in single cases of polyarteritis nodosa, necrotizing vasculitis, and erysipelas. Six cases (16%) had no definite underlying disease. The mean age of all patients was 57 years (range 32-86 years), and 34 patients (89%) were women. Of the five major categories identified, lipomembranes lining macrocysts and microcysts were most prominent in the venous insufficiency- and morphea-related cases and were much less prominent in erythema nodosum, lupus panniculitis, and necrobiosis lipoidica, which generally showed histopathologic findings typical of these disorders. In addition to lining the macrocystic and microcystic cavities formed in the fat lobules, lipomembranes were prominent in areas of septal fibrosis in all cases associated with morphea and necrobiosis lipoidica and in 35% and 25% of venous insufficiency- and erythema nodosum-related cases, respectively. In lupus panniculitis, lipomembranes were most prominent in areas of hyaline necrosis. We conclude that lipomembranous fat necrosis is most likely a nonspecific form of ischemic fat degeneration that may be induced by various clinical entities. This change is most often seen in venous insufficiency-associated chronic sclerotic plaques typically observed in middle-aged obese women, and we propose the term stasis-associated lipomembranous panniculitis (SALP) to describe this most common form of lipomembranous fat necrosis.

International Journal of DermatologyVolume 35, Issue 1 p. 1-8 SUBCUTANEOUS PANNICULITIC T-CELL LYMPHOMA CHIN-YAO ERIC WANG, CHIN-YAO ERIC WANG M.D. From the Department of Dermatology and the Divisions of Anatomic Pathology and Hematopathology, Mayo Clinic and Mayo Foundation, Rochester, Minnesota. Visiting clinician at Department of Dermatology, Mayo Clinic; present address: National Defense Medical Center &C Tri-Service General Hospital, Taiwan, R.O.C.Search for more papers by this authorW.P. DANIEL SU, Corresponding Author W.P. DANIEL SU M.D. From the Department of Dermatology and the Divisions of Anatomic Pathology and Hematopathology, Mayo Clinic and Mayo Foundation, Rochester, Minnesota.W.P. Daniel Su, M.D., Department of Dermatology, Mayo Clinic, 200 First Street SW, Rochester, MN 55905.Search for more papers by this authorPAUL J. KURTIN, PAUL J. KURTIN M.D. From the Department of Dermatology and the Divisions of Anatomic Pathology and Hematopathology, Mayo Clinic and Mayo Foundation, Rochester, Minnesota.Search for more papers by this author CHIN-YAO ERIC WANG, CHIN-YAO ERIC WANG M.D. From the Department of Dermatology and the Divisions of Anatomic Pathology and Hematopathology, Mayo Clinic and Mayo Foundation, Rochester, Minnesota. Visiting clinician at Department of Dermatology, Mayo Clinic; present address: National Defense Medical Center &C Tri-Service General Hospital, Taiwan, R.O.C.Search for more papers by this authorW.P. DANIEL SU, Corresponding Author W.P. DANIEL SU M.D. From the Department of Dermatology and the Divisions of Anatomic Pathology and Hematopathology, Mayo Clinic and Mayo Foundation, Rochester, Minnesota.W.P. Daniel Su, M.D., Department of Dermatology, Mayo Clinic, 200 First Street SW, Rochester, MN 55905.Search for more papers by this authorPAUL J. KURTIN, PAUL J. KURTIN M.D. From the Department of Dermatology and the Divisions of Anatomic Pathology and Hematopathology, Mayo Clinic and Mayo Foundation, Rochester, Minnesota.Search for more papers by this author First published: January 1996 https://doi.org/10.1111/j.1365-4362.1996.tb01606.xCitations: 58 AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat Citing Literature Volume35, Issue1January 1996Pages 1-8 RelatedInformation

Dr. Rafool correctly points out the difficulty in determining causality based on clinical observations. The possibility of fluphenazine causing the muscle damage was considered; however, no reports have described this relationship, although eight reports have described other phenothiazines associated with rhabdornyolysis.1Reis J Felten P Rumbach L Collard M Hyperthermia with acute rhabdomyolysis in a psychotic treated with neuroleptics.Rev Neurol (Paris). 1983; 139: 595-596PubMed Google Scholar, 2Denborough MA Collins SP Hopkinson KC Rhabdomyolysis and malignant hyperpyrexia.BMJ. 1984; 288: 1878Crossref PubMed Scopus (41) Google Scholar, 3Chichmanian RM Fuzibet JG Mignot G Dujardin P Acute rhabdomyolysis induced by fenoverine: 2 cases [letter].Ann Med Interne (Paris). 1990; 141: 490-491PubMed Google Scholar, 4Hebuterne X Chichmanian RM Cohen HL Rampal P Acute rhabdomyolysis due to fenoverine [letter].Gastroenterol Clin Biol. 1991; 15: 861-862PubMed Google Scholar, 5Dutertre JP Asselin F Jonville AP Benhamou C Autret E Rhabdomyolysis with acute renal insufficiency caused by fenoverine [letter].Ann Med Interne (Paris). 1991; 142: 553-554PubMed Google Scholar, 6Benamouzig R Chaussade S Roche H Aubert A Fiessinger JN Carlet J et al.Acute rhabdomyolysis and necrotizing enterocolitis after ingestionof fenoverine [letter].Gastroenterol Clin Biol. 1992; 16: 719-720PubMed Google Scholar, 7Sultan S Lesgourgues B el Attar Y Fauvelle F Delas N Acute rhabdomyolysis due to fenoverine (Spasmopriv): a case and review of the literature [letter].Therapie. 1992; 47: 443PubMed Google Scholar, 8Hardin JM Guillebaud JC Lallement PY Matta B Andrejak M Rhabdomyolysis associated to fenoverine therapy and complicated by acute renal failure [letter].Therapie. 1992; 47: 165-166PubMed Google Scholar Two reports1Reis J Felten P Rumbach L Collard M Hyperthermia with acute rhabdomyolysis in a psychotic treated with neuroleptics.Rev Neurol (Paris). 1983; 139: 595-596PubMed Google Scholar, 2Denborough MA Collins SP Hopkinson KC Rhabdomyolysis and malignant hyperpyrexia.BMJ. 1984; 288: 1878Crossref PubMed Scopus (41) Google Scholar noted several signs consistent with the neuroleptic malignant syndrome, a known cause of muscle damage. Unfortunately, not all the authors had an opportunity to observe their patients before the onset of symptoms; thus, the mechanism that caused the rhabdomyolysis is less obvious. In each of the reports, however, the patients had recently begun taking fenoverine, and discontinuation of use of that drug was considered an important part of the treatment. In one patient, use of the drug was reinstituted, and rhabdomyolysis promptly redeveloped. In contrast, my patient had been taking fluphenazine at the same dosage for years and still receives this treatment. He was closely observed in the hospital when his problems began, and he specifically had no leukocytosis, fever, spasms, or seizures consistent with the neuroleptic malignant syndrome. He continues to take the phenothiazine at the same dosage and has had no clinical or laboratory evidence of other recurrences of rhabdomyolysis. Although I cannot be unequivocally sure, the evidence presented in the case report strongly supports the conclusion that correction of the hyponatremia was the proximate cause of the rhabdomyolysis. Causes of RhabdomyolysisMayo Clinic ProceedingsVol. 70Issue 12PreviewTo the Editor: I read with interest the article by Dr. Rizzieri entitled “Rhabdomyolysis After Correction of Hyponatremia Due to Psychogenic Polydipsia,” which was published in the May 1995 issue of the Mayo Clinic Proceedings (pages 473 to 476). In that article, he attributed rhabdomyolysis to rapid correction of the patient's hyponatremia. I wonder why Dr. Rizzieri did not attribute it to the patient's psychotropic medicine, fluphenazine decanoate. It seems that a phenothiazine antipsychotic drug is more likely to cause this problem than is rapid correction of the hyponatremia. Full-Text PDF