Does chloroquine therapy of porphyria cutanea tarda influence liver pathology?

BACKGROUND: Porphyria cutanea tarda (PCT) is regularly associated with changes in liver tissue. On the other hand, systematic investigations are lacking on whether there is a correlation between the severity of liver damage and chloroquine treatment. PATIENTS AND METHODS: During a 20-year period, liver biopsies were obtained in 89 patients with PCT confirmed by biochemical analysis of urine and feces and low-dose chloroquine therapy. Seventeen patients with alcohol-induced liver disease were excluded. In 8 of 63 patients, only a single biopsy was available. Classification of liver damage was performed according to the Riedel score. Electron microscopy was available from 24 patients. In a second group of patients, the HFE status was investigated and Berlin blue stains of liver biopsies were performed. RESULTS: There was no correlation between the duration of cutaneous symptoms and liver pathology. After 12 months chloroquine treatment, 45 patients (81%) disclosed an improvement of liver pathology, nine (16%) had no change, and a worsening was observed in one patient (3%). All patients achieved a complete clinical and biochemical remission. In 13 of 16 patients with a relapse, there was again a deterioration of liver damage. Patients with HFE mutations had a significant higher risk (P < 0.05) for hepatic siderosis. CONCLUSIONS: The severity of liver damage was not correlated with the disease duration. Chloroquine treatment resulted in PCT remission (clinical and biochemical) and in 81% to an improvement of liver morphology.

Cutaneous Langerhans cell histiocytosis with subsequent development of haematological malignancies. Report of two cases.

Adult cutaneous Langerhans cell histiocytosis (LCH) is a rare disease. We report two cases illustrating the variability of the clinical presentation and the response to treatment. In both cases a remission was achieved: in one case a partial remission with psoralen plus UVA irradiation (PUVA) and methotrexate plus topical corticosteroid ointment; in the other case by treatment with thalidomide. Despite a therapeutic response, both patients later developed haematological malignancies: a chronic myelo-monocytic leukaemia and an acute lymphatic leukaemia. In conclusion, patients with adult cutaneous LCH should be monitored carefully so that a secondary malignancy is not overlooked.

[Hepatitis C, hemochromatosis and porphyria cutanea tarda]. / Hepatitis C und Hämochromatose bei Porphyria cutanea tarda.

Porphyria cutanea tarda (PCT) is characterized by decreased activity of the enzyme uroporphyrinogen decarboxylase (URO-D) and the accumulation of uro- and heptaporphyrins in the liver. Apart from increased alcohol exposure and certain drugs, PCT is associated with antibodies to the hepatitis C virus (HCV), with its prevalence increasing from Northern (8-10%) to Southern Europe (71 to 91%). Chronic HCV-infection is thus considered to be a major trigger for PCT and PCT is said to be an important extrahepatic manifestation of HCV-infection in predisposed individuals. Iron overload is common in PCT. Iron is an inhibitory co-factor of URO-D activity in hepatocytes. Accordingly, in support of the critical role of iron, the clinical efficacy of iron removal is coupled to an improvement of hepatic URO-D activities. Up to two thirds of Saxon patients with PCT carry the classical hemochromatosis (HFE) mutations (C282Y and/or H63D). HFE genotyping can help to further classify patients with PCT and associated hemochromatosis. Simple or compound heterozygosity of HFE mutations does not affect the therapeutic response to chloroquine in PCT. Since Patients carrying homozygous mutations (C282Y/C282Y) with hemochromatosis and PCT do not respond to chloroquine, phlebotomy should be first-line treatment to remove toxic iron.

Topical PDGF-BB results in limited healing in a patient with Werner's syndrome and chronic leg ulcers.

Impaired wound healing is a feature of Werner's syndrome. Treatment of one such patient with painful chronic leg ulcers included topical application of PDGF-BB. Granulation increased slightly, enabling full-thickness skin grafting to take place.

Interstitial granulomatous dermatitis with plaques and arthritis.

Interstitial granulomatous dermatitis and arthritis (IGDA) is a rare disease entity with female predominance. The case of a 53-year-old woman with erythemas, plaques and nodules associated with polyarthritis is presented. She was treated with cyclosporin A, with improvement of the joint affliction and complete clearance of skin lesions. The differential diagnosis of IGDA is discussed briefly.

Mineral oil granuloma of the penis.

We report a 30-year-old-patient with penile sclerosing lipogranuloma following injections of Vaseline. He was successfully treated by complete surgical removal of the subcutaneous material and excision of atrophic skin, followed by penoplasty. Temporary impairment of wound healing was overcome by application of topical carbon dioxide gas. A brief review on international literature is given.

Polydactylous Bowen's disease.

Malignant nail tumours are rare. We report on a 52-year-old patient with chronic verrucous lesions of the nail bed of fingers and toes. Nail biopsy revealed polydactylous Bowen's disease. This is the first case reported with hand and foot lesions.

Liposomal daunorubicin in tumor stage cutaneous T-cell lymphoma: report of three cases.

PURPOSE: Advanced cutaneous T-cell lymphoma (CTCL) is a hard-to-treat condition. Complete response is rare even with polychemotherapy. The use of liposomal formulation anti-cancer drugs can improve the efficacy and the risk-benefit ratio. Liposomal doxorubicin was shown to be effective as a second-line treatment in CTCL. There is no data available on another classical anthracycline, daunorubicin, when given in liposomal formulation as a monotherapy. METHODS: Monotherapy with liposomal-encapsulated daunorubicin (DNX) was given as a monotherapy once a month at 20 mg/m(2) three times to achieve a clinical response. In the case of limited response the drug was given once every 3 weeks and a dose increase was performed. Three patients were treated. RESULTS: A complete response was achieved in one patient (dosage 20 mg/m(2 )once per month). Two other patients achieved a partial response. The final outcome was disease-free survival of more than 10 months in the patient with a complete response and survival of >8 months and 6 months in those with a partial response. Adverse effects were grade 4 anemia in one patient, lymphopenia grade 2 with grade 1 anemia, and grade 1 lymphopenia in the other patients. CONCLUSION: This is the first report on DNX monotherapy in CTCL. In a small group of three patients a response rate of 100% was achieved with one complete response. DNX seems to be another option in advanced cases of CTCL.

Merkel cell carcinoma--a retrospective analysis of 17 cases.

OBJECTIVE: To report clinical experience with the rare neuroendocrine Merkel cell carcinoma of the skin. SUBJECTS AND SETTING: Seventeen patients with Merkel cell carcinoma of the skin treated at the Departments of Dermatology and ENT, Krankenhaus Dresden-Friedrichstadt, Dresden, Germany, during the years 1984-2000 were evaluated. METHODS: A retrospective analysis was performed. Age and sex distribution, clinical data and therapy were collected. Outcome measures including overall survival, tumour-free survival and relapse-free survival were determined. RESULTS: Six male and 11 female patients with an age range of 68-90 years (mean age 73.3 years) were identified. The primary tumour localization was head and neck region (n = 8), upper limbs (8), lower limbs (1). Twelve patients presented in tumour stage I, three in stage II and one in stage III. First line therapy was complete surgical excision with wide margins in 16 patients followed by loco-regional radiation in 12 of 16 cases. In 16 patients follow up data were available. After primary treatment complete response was achieved in 14 of 16 patients (87.5%), two patients had a partial response. The median of relapse-free survival was 44 weeks [mean +/- standard deviation: (44 +/- 118) weeks]. The median of overall survival was 102 weeks [mean +/- standard deviation: (137 +/- 94) weeks]. Three patients with a PR after primary treatment had a median overall survival of only 48 weeks [mean +/- standard deviation: (51 +/- 20) weeks]. CONCLUSIONS: Primary surgical treatment with wide excision combined with radiotherapy seems to be a reasonable first-line treatment but prospective controlled multicentre trials are necessary for validation.

C282Y and H63D mutation of the hemochromatosis gene in German porphyria cutanea tarda patients.

BACKGROUND AND AIMS: Patients with porphyria cutanea tarda (PCT) have a susceptibility to reversible inactivation of hepatocyte uroporphyrinogen decarboxylase, which can be triggered by alcohol, hepatitis C virus, and other agents. Inherited factors that may predispose to PCT include the C282Y mutation in the hemochromatosis (HFE) gene. METHODS: We analyzed the hemochromatosis mutations C282Y and H63D in liver biopsies and serum samples of 190 German patients (mean age 48+/-12.5 years) with sporadic PCT. The hepatic iron concentration was determined within the liver tissue. Age-matched healthy blood donors (115 donors) served as controls. RESULTS: The C282Y and H63D mutations were found in 75 (39%) and 85 (45%) of 190 patients with PCT, respectively. Twenty-two patients (12%) were homozygous for the C282Y mutation, and eighteen patients (9%) were compound heterozygotes, displaying both the C282Y and the H63D mutation. Within the control group, 3 of 115 patients were heterozygous for C282Y (3%) and 12 for H63D (10%). Serum and hepatic iron, ferritin, transferrin saturation, or liver enzymes did not differ significantly between patients with or without HFE mutations. CONCLUSIONS: The high frequency of homo- and heterozygosity for the C282Y and H63D alleles strongly suggests that these mutations are important predisposing factors for PCT in German patients.

[Transitory acantholytic dermatosis (Grover's disease) in sarcoptic scabies infection]. / Transitorische akantholytische Dermatose (Grover) bei Sarcoptes scabiei-Infektion.

An eighty-two year old patient had scabies and transient acantholytic dermatosis (TAD, Grover's disease) at the same time. Persistent itching papules after lindane therapy finally led us to the microscopic diagnosis of TAD. Different trigger mechanisms can apparently induce the typical acantholysis. In addition to solar radiation, tumors and tumor therapy-dependent conditions, cutaneous infections have been implicated reports (Demodex folliculorum, Malassezia furfur) as causes of TAD. This may be the first report about a relationship between TAD and mite infection with Sarcoptes scabiei.

[Sterile eosinophilic pustulosis (Ofuji). A rare entity in Europe]. / Sterile eosinophile Pustulose (Ofuji). Eine in Europa seltene Entität.

This case report refers to a German patient with sterile eosinophilic pustulosis of the Ofuji type (SEP), which is rarely described in non-Japanese humans. The distinctive histomorphology, with intraepidermal eosinophilic abscesses and eosinophilic folliculitis, is complemented in this patient by marked eosinophilia, evident eosinophilic bone marrow reaction and involvement of the oral mucosa with eosinophilic spongiosis, which is a feature that had not previously been reported. Possible transitions between cutaneous and internal hypereosinophilic syndromes are discussed. Despite the initial good effect of topical corticosteroids on the cutaneous changes, long-term follow-up to check for internal involvement is necessary.

Low prevalence of hepatitis C virus infection in porphyria cutanea tarda in Germany.

Previous studies from Spain, Italy, and France have demonstrated a high prevalence (71% to 91%) of antibodies against hepatitis C virus in patients with porphyria cutanea tarda (PCT). To determine the role of hepatitis C virus (HCV) in PCT in Germany, we have assessed the prevalence of antibodies against HCV and hepatitis B virus (HBV) in 106 patients (mean age, 60 +/- 14 years) with the disease. Eight of 106 patients (8%) were positive for HCV antibodies and HCV RNA using second-generation enzyme-linked immunosorbent assay (ELISA), recombinant immunoblot assay, and polymerase chain reaction. Antibodies against HBV core antigen were found in 14 patients (13%). Of the patients with antibodies against HCV alanine transaminase (ALT) (aspartate transaminase [AST]) levels above normal occurred in 71% (86%). Because elevated ALT (AST) levels were also found in 51% (64%) of 88 patients without markers of HCV or HBV, we suggest that liver damage in PCT may exist in absence of these viruses. This is supported by the finding that in patients without HCV or HBV markers, higher serum ALT and AST activities were found in patients with overt disease or relapse (ALT, 59 +/- 44 U/L; AST, 37 +/- 21 U/L), whereas patients in remission displayed significantly lower serum enzyme activities (ALT, 16 +/- 8 U/L; AST, 16 +/- 7 U/L), (P < .001). These results indicate that HCV infection does not play a major role in the pathogenesis of PCT in Germany.