Diagnostic utility of serum melatonin levels in systemic lupus erythematosus: a case-control study.

Systemic lupus erythematosus (SLE) is a chronic systemic autoimmune inflammatory disease and early diagnosis is of clinical and therapeutic importance. Melatonin is an endogenous endolamine hormone that plays an important role in the immune system due to its anti-inflammatory action. This study was designed to assess serum melatonin levels in SLE patients and to evaluate the possible correlation between serum melatonin and patients' baseline characteristics. A case-control study was performed on 50 SLE patients (48 females and 2 males), diagnosed according to the revised 1997 ACR Criteria, and 25 healthy controls (24 females and 1 male), matched by age and sex. Daily serum melatonin levels were investigated in all participants using human melatonin enzyme linked immunosorbent assay (ELISA) kit (MYBIOSOURCE (MBS), United States). Serum melatonin concentration was significantly lower in patients with SLE compared to healthy controls (19.17±6.86 pg/mL vs 23.26±6.71 pg/mL, p=0.017). Serum melatonin concentration ≤18.51 pg/mL was the optimum cut off value to differentiate between SLE patients and healthy controls with an accuracy of 69.3%, a sensitivity of 66%, and a specificity of 76%. The positive predictive value (PPV) at pretest 50% was 73.3% and PPV at pretest 90% was 96.1%; the negative predictive value (NPV) at 10% was 95.3%. Patients' characteristics were not significantly correlated with serum melatonin concentrations using multiple logistic regression analysis. Serum melatonin was a valid measure to differentiate between SLE patients and healthy controls with good accuracy, sensitivity and specificity and PPV and NPV. There was no significant correlation between serum melatonin concentrations and patients' baseline characteristics.

Pseudoporphyria: a clinical and biochemical study of 20 patients.

OBJECTIVE: To describe the clinical and laboratory findings in patients with pseudoporphyria. PATIENTS AND METHODS: This 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. RESULTS: Twenty 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. CONCLUSION: Pseudoporphyria 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.

Monoclonal gammopathies and associated skin disorders.

The monoclonal gammopathies are characterized by clonal proliferation of plasma cells and other clonally related cells in the B-cell lineage. These disorders include monoclonal gammopathy of undetermined significance, multiple myeloma, Waldenström macroglobulinemia, heavy chain diseases, plasmacytoma, and primary amyloidosis. Many skin disorders have been described in association with monoclonal gammopathies. This article provides an introduction to the definition, detection, natural course, and spectrum of monoclonal gammopathies and a brief discussion of pathogenesis. The article also reviews the skin disorders associated with monoclonal gammopathies, categorizes the association, and evaluates the strength of the association.

Recognizing cutaneous drug eruptions. Reaction patterns provide clues to causes.

Cutaneous drug eruptions caused by use of various medications are becoming more and more common. Fortunately, most such eruptions resolve when the offending medication is withdrawn. Nonetheless, it is vital that physicians can recognize drug-related eruptions and ascertain the degree of severity, since some reactions are potentially fatal. A carefully taken drug history and a thorough physical examination are crucial in this effort.

Subcorneal pustular dermatosis: a clinical study of ten patients.

Subcorneal pustular dermatosis of Sneddon and Wilkinson (SPD) is a unique clinical and histologic entity. This disorder has been reported in association with monoclonal gammopathy and IgA pemphigus. We report ten additional cases of SPD and determine the frequency of monoclonal gammopathy and IgA pemphigus in patients with SPD and investigate the relationship of this entity with other dermatoses characterized histologically by a subcorneal pustule. The medical records of patients with SPD evaluated at the authors' institution from 1980 through 1995 were reviewed retrospectively. Medical records of twenty patients with pustular psoriasis were reviewed for comparison. Ten patients met the criteria for SPD. Their average age at diagnosis was 66 years. The characteristic flaccid pustules were often generalized and had a tendency to involve the flexural areas. Serum monoclonal gammopathy was present in four patients: three with IgA and one with IgG. On direct immunofluorescence examination, three patients had IgA deposits in the intercellular spaces. None of the patients exhibited both monoclonal gammopathy and IgA deposits. Repeated direct immunofluorescence studies were necessary to detect IgA pemphigus in one patient. SPD is a distinct clinical entity. The findings of IgA deposits intercellularly on immunofluorescence and monoclonal gammopathy may help to further identify this entity.

Clinicopathologic correlation of hypocomplementemic and normocomplementemic urticarial vasculitis.

BACKGROUND: Urticarial vasculitis is characterized by persistent urticarial lesions with histologic evidence of leukocytoclastic vasculitis. Hypocomplementemic urticarial vasculitis (HUV) is a distinct clinical entity in a subset of patients with urticarial vasculitis. OBJECTIVE: We examined presentation of urticarial vasculitis and factors predictive of connective tissue disease. METHODS: The clinical, histologic, and immunologic characteristics of 132 patients with urticarial vasculitis seen at the Mayo Clinic were examined, and features of the hypocomplementemic patients were compared with those of the normocomplementemic patients. RESULTS: Twenty-four patients (18%) had hypocomplementemia; all were female. Interstitial dermal neutrophilia was seen in 19 biopsy specimens (83%). On direct immunofluorescence (DIF) testing of lesional skin, 23 patients (96%) had a continuous strong granular deposition of immunoreactants along the basement membrane zone compatible with lupus erythematosus in addition to vascular fluorescence. Systemic lupus erythematosus (SLE) was present or occurred in 13 (54%). One hundred eight patients (82%) had normocomplementemia; 65 (60%) were female. Interstitial dermal neutrophilia was seen in 11 of 26 (42%) randomly selected biopsy specimens. On DIF, one patient (1%) had the lupus band. SLE occurred in three patients (3%). CONCLUSION: Patients with HUV were more likely to be female, to have diffuse neutrophilia on biopsy specimens stained with hematoxylin and eosin, to have continuous strong granular deposition of immunoreactants along the basement membrane zone on DIF, and to have SLE than normocomplementemic patients. We submit that HUV represents a subset of SLE with shared clinical, laboratory, and immunologic features.

Hydroxyurea-induced leg ulceration in 14 patients.

BACKGROUND: Hydroxyurea is an antineoplastic agent commonly used to treat myeloproliferative disorders and other nonneoplastic conditions. OBJECTIVE: To further define the typical features of hydroxyurea-related cutaneous ulcers of the leg. DESIGN: Retrospective, descriptive study of the medical records of patients who developed leg ulcers while receiving hydroxyurea therapy. SETTING: A tertiary care medical center. PATIENTS: Patients with myeloproliferative disorders who were treated with hydroxyurea. RESULTS: 14 patients with extremely painful leg ulcers were identified. The most common ulcer site was the malleoli. Multiple ulcers were seen in 64% of patients. Patients had received hydroxyurea for an average of 6 years before ulcers developed. All ulcers healed after discontinuation of hydroxyurea treatment, and 2 patients developed ulcers after treatment was restarted. CONCLUSION: Hydroxyurea induces painful leg ulcers that are usually difficult to treat and require cessation of hydroxyurea therapy.

Malignant pyodermas revisited.

The concept of malignant pyoderma (MP) has created controversy since its origin. The distinction of this disease from pyoderma gangrenosum was based on clinical criteria and response to treatment. Herein we discuss our current ideas on this entity and its possible relationship to Wegener's granulomatosis (WG). Follow-up data from the three original cases of MP are reported, as well as additional clinical and laboratory data from cases subsequently thought to represent MP. Many of these cases have similar clinical features such as facial and periauricular ulceration and occasionally signs or symptoms of WG, including positive titers of antineutrophil cytoplasmic antibodies (with a diffuse cytoplasmic staining pattern) (cANCA). MP represents a distinctive clinical disorder and may be a dermal manifestation of WG. Some cases of MP may represent pyoderma gangrenosum or other undefined systemic illnesses. Such cases of WG can be distinguished on the basis of clinical, histopathologic, and laboratory evidence including cANCA titers. MP should no longer be used as a final clinical diagnosis.

Cutaneous manifestations of Churg-Strauss syndrome: a clinicopathologic correlation.

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.

Cutaneous periarteritis nodosa: a clinicopathological study of 79 cases.

Cutaneous periarteritis nodosa (PAN) is a well-recognized entity characterized by tender subcutaneous nodules and livedo that may ulcerate. The pathogenesis of cutaneous PAN is not known. The objective of the study was to evaluate the clinical and histological features of 79 cases of cutaneous PAN and to investigate any clinical, pathological and immunological differences that may distinguish those cases likely to have a prolonged course. A retrospective analysis of 79 cases was conducted. Thirty-nine patients had ulcers during the course of their illness. Women were affected more than men. Painful nodules on the lower extremities, with oedema and swelling, were the most common clinical finding; 22% of patients had some evidence of neuropathy. Most of the laboratory findings were non-specific. There was no evidence for hepatitis B infection and hepatitis C infection was present in only one patient. Most patients (60%) had no associated medical condition. The disease course was prolonged but benign, and systemic PAN did not develop in any patient. Corticosteroids given systemically induced remission in most acute cases. The ulcerative form of disease was more prolonged and frequently associated with neuropathy.

Hydroxyurea dermopathy: a unique lichenoid eruption complicating long-term therapy with hydroxyurea.

BACKGROUND: Hydroxyurea is usually a well tolerated antitumor agent. OBJECTIVE: Our purpose was to describe a distinct clinical and histologic eruption in patients receiving long-term hydroxyurea therapy. METHODS: The clinical, histologic, and immunopathologic features of six patients with hydroxyurea dermopathy are described. RESULTS: Three women and three men were identified. The average age was 61 years. Hydroxyurea had been used for an average of 5 years. Lichenoid papules, telangiectasia, and poikilodermatous lesions on the dorsal hands and digits were the most common findings. Interface dermatitis, focal lichenoid reaction with epidermal atrophy, and Civatte bodies were the most common histologic findings. Endothelial swelling also was noted. Cytoid staining with multiple conjugates was the most common immunopathologic finding. Four patients showed significant improvement after discontinuation of hydroxyurea. CONCLUSION: A distinct cutaneous reaction to long-term administration of hydroxyurea has been characterized. Cessation of treatment is necessary for healing or improvement. We have designated this eruption hydroxyurea dermopathy.

Indeterminate cell histiocytosis treated successfully with 2-chlorodeoxyadenosine.

We report the case of a 54-year-old man with a ten-year history of a generalized papular eruption consistent with the diagnosis of indeterminate cell histiocytosis. The patient responded favorably to a course of treatment with 2-chlorodeoxyadenosine.

Anti-epiligrin (laminin 5) cicatricial pemphigoid and lung carcinoma: coincidence or association?

Anti-epiligrin cicatricial pemphigoid (CP) is a rare subset of CP in which patients have IgG autoantibodies directed against the dermal side of skin split by 1 mol/L NaCl. The antibodies react against epitopes in the lowermost portions of the lamina lucida, and immunoprecipitate epiligrin (laminin 5) in human keratinocyte extracts. We report a patient with this uncommon form of CP, who, following an 8-year period of well-controlled disease, experienced a severe flare in symptoms coincident with development of lung carcinoma. This raises the possibility of an association, in this case, between anti-epiligrin CP and lung carcinoma.

Chronic hepatitis C, cryoglobulinemia, and cutaneous necrotizing vasculitis. Clinical, pathologic, and immunopathologic study of twelve patients.

BACKGROUND: Several patients with chronic hepatitis C infection and cutaneous vasculitis have been described. OBJECTIVE: The objective of this study was to define better the features of necrotizing vasculitis and mixed cryoglobulinemia in patients with hepatitis C infection. METHODS: A retrospective review of 611 patients with hepatitis C antibodies was conducted. Patients with clinical and histopathologic findings of cutaneous necrotizing vasculitis were identified. Clinical, histologic, and laboratory data were recorded. RESULTS: Twelve patients with necrotizing vasculitis and chronic hepatitis C infection were identified. Palpable purpura was the most common clinical presentation. Onset of skin lesions was usually more than 10 years after infection. The lower extremities were affected in all patients. Cryoglobulinemia of the mixed type II was present in 10 of 11 patients. Liver function tests were evaluated at the time of vasculitis in most of the patients. Rheumatoid factor was elevated in all nine patients tested. Total complement was decreased in seven of nine patients, and C4 was decreased in six of seven patients. CONCLUSION: Cutaneous vasculitis associated with cryoglobulinemia and hypocomplementemia is not uncommon in the course of chronic active hepatitis C infection. The triad of necrotizing vasculitis, chronic hepatitis C infection, and cryoglobulinemia occurs late after initial infection with hepatitis C. Antibodies to hepatitis C virus should be determined in a patient with necrotizing vasculitis, especially if liver function tests are elevated.

Aleukemic monocytic leukemia cutis.

Aleukemic leukemia cutis is a rare condition in which leukemic cells invade the skin before they appear in peripheral blood or bone marrow specimens. Herein we describe a 67-year-old man who underwent assessment because of papules and nodules on his back and lower extremities. A biopsy of these lesions confirmed a dense, predominantly monocytic infiltrate of the dermis and subcutaneous tissue. Immunohistochemical stains were positive for CD43 (Leu-22) as well as monocytic markers. Bone marrow and peripheral blood examinations failed to reveal leukemia. Treatment was based on the results of the skin biopsy, and the patient is doing well 1 year after therapy.

The use of full-thickness skin grafts for the repair of defects on the dorsal hand and digits.

BACKGROUND: The hand is a complex part of the human body and plays an important role in our everyday lives. It is critical to preserve manual function when repairing surgical defects on the dorsum of the hand and digits. OBJECTIVE: To demonstrate the effectiveness of the full-thickness skin graft (FTSG) in the repair of surgical defects on the dorsum of the hand and digits. METHODS: Through a retrospective review of photographic and written records and person-to-person interviews, the authors evaluated 19 patients who underwent FTSG repair of 21 defects on the dorsum of the hand and digits after Mohs micrographic surgery. RESULTS: In all cases, the FTSG was durable, yielded good cosmetic results, and maintained normal function of the hand. CONCLUSION: The FTSG is a good option for repairing surgical defects on the dorsum of the hand and digits.

Chronic hepatitis C and skin diseases: a review.

OBJECTIVE: To emphasize the ongoing role of chronic hepatitis C virus (HCV) infection in the cause or exacerbation of severe dermatologic disorders. DESIGN: We present two case reports to outline the pertinent findings in hepatitis C-related cryoglobulinemia, leukocytoclastic vasculitis, and lichen planus and discuss the main disorders associated with chronic HCV infection. RESULTS: Chronic HCV infection has recently been recognized in association with various skin disorders. The most commonly reported association is the triad of leukocytoclastic vasculitis, cryoglobulinemia, and chronic HCV infection. Other cutaneous disorders associated with HCV infection include porphyria cutanea tarda, lichen planus, erythema nodosum, urticaria, erythema multiforme, and polyarteritis nodosa. CONCLUSION: Patients with onset or exacerbation of these disorders should undergo assessment for HCV infection.

Jadassohn-Lewandowski syndrome (pachyonychia congenita).

Pachyonychia congenita is an uncommon autosomal dominant disorder with variable expression. Symmetrical nail hypertrophy, present in nearly all cases, is accompanied by dyskeratosis and dysplasia of other ectodermal tissues. This article reviews the genetics, clinical manifestations, histopathology, and treatment of pachyonychia congenita. Many clinical features have been reported in association with this syndrome. From a review of the literature, we propose criteria for the diagnosis of pachyonychia congenita using the more important of these clinical manifestations.