Cyclosporine-induced erythromelalgia.

Erythromelalgia is a rare syndrome characterised by recurrent erythema, heat and burning pain in the extremities. There are two types: primary (genetic) and secondary (toxic, drug-related or associated with other diseases). We report a 42-year-old woman who developed erythromelalgia after taking cyclosporine for myasthenia gravis. Although exact mechanism for this rare adverse effect is unclear, it is reversible, and so clinicians should be aware of the association . Additional use of corticosteroids could aggravate cyclosporine's toxic effects.

Hormone replacement therapy-induced pain and redness of the feet.

We report the first case, to our knowledge, of a patient who developed erythromelalgia after receiving oestrogen-progestin replacement therapy (Femoston). The patient had complete remission after taking glycyrrhizin and pregabalin for 3 months. This case expands the spectrum of erythromelalgia and provides a therapeutic option.

Simvastatin-induced erythromelalgia: less is more.

We describe a case of a woman with uncomplicated Type 2 diabetes mellitus, presenting with severe burning pains and intense redness of the legs, for which only cooling could provide relief. Although the description was classic of erythromelalgia, the lack of familiarity of the disorder caused considerable doctor's delay as well as the erroneous advice to start pain killers and amitriptyline. However, empirical discontinuation of simvastatin made all symptoms disappear. Erthyromelalgia is a rare but debilitating disease which is diagnosed by exclusion only. It usually occurs as a secondary feature to (hematologic) malignant disorders, autoimmune diseases or, infections or, most notoriously, to pharmacological agents. One of the latter might be simvastatin, and possibly all HMG CoA Reductase inhibitors.

Corneal Confocal Microscopy Detects Small Fibre Neuropathy in Patients with Upper Gastrointestinal Cancer and Nerve Regeneration in Chemotherapy Induced Peripheral Neuropathy.

There are multiple neurological complications of cancer and its treatment. This study assessed the utility of the novel non-invasive ophthalmic technique of corneal confocal microscopy in identifying neuropathy in patients with upper gastrointestinal cancer before and after platinum based chemotherapy. In this study, 21 subjects with upper gastrointestinal (oesophageal or gastric) cancer and 21 healthy control subjects underwent assessment of neuropathy using the neuropathy disability score, quantitative sensory testing for vibration perception threshold, warm and cold sensation thresholds, cold and heat induced pain thresholds, nerve conduction studies and corneal confocal microscopy. Patients with gastro-oesophageal cancer had higher heat induced pain (P = 0.04) and warm sensation (P = 0.03) thresholds with a significantly reduced sural sensory (P<0.01) and peroneal motor (P<0.01) nerve conduction velocity, corneal nerve fibre density (CNFD), nerve branch density (CNBD) and nerve fibre length (CNFL) (P<0.0001). Furthermore, CNFD correlated significantly with the time from presentation with symptoms to commencing chemotherapy (r = -0.54, P = 0.02), and CNFL (r = -0.8, P<0.0001) and CNBD (r = 0.63, P = 0.003) were related to the severity of lymph node involvement. After the 3rd cycle of chemotherapy, there was no change in any measure of neuropathy, except for a significant increase in CNFL (P = 0.003). Corneal confocal microscopy detects a small fibre neuropathy in this cohort of patients with upper gastrointestinal cancer, which was related to disease severity. Furthermore, the increase in CNFL after the chemotherapy may indicate nerve regeneration.

Neuroprotective effect of erythropoietin against pressure ulcer in a mouse model of small fiber neuropathy.

An increased risk of skin pressure ulcers (PUs) is common in patients with sensory neuropathies, including those caused by diabetes mellitus. Recombinant human erythropoietin (rhEPO) has been shown to protect the skin against PUs developed in animal models of long-term diabetes. The aim of this work was to determine whether rhEPO could prevent PU formation in a mouse model of drug-induced SFN. Functional SFN was induced by systemic injection of resiniferatoxin (RTX, 50 µg/kg, i.p.). RhEPO (3000 UI/kg, i.p.) was given the day before RTX injection and then every other day. Seven days after RTX administration, PUs were induced by applying two magnetic plates on the dorsal skin. RTX-treated mice expressed thermal and mechanical hypoalgesia and showed calcitonin gene-related peptide (CGRP) and substance P (SP) depletion without nerve degeneration or vascular dysfunction. RTX mice developed significantly larger stage 2 PUs than Vehicle mice. RhEPO prevented thermal and mechanical hypoalgesia and neuropeptide depletion in small nerve fibers. RhEPO increased hematocrit and altered endothelium-dependent vasodilatation without any effect on PU formation in Vehicle mice. The characteristics of PUs in RTX mice treated with rhEPO and Vehicle mice were found similar. In conclusion, RTX appeared to increased PU development through depletion of CGRP and SP in small nerve fibers, whereas systemic rhEPO treatment had beneficial effect on peptidergic nerve fibers and restored skin protective capacities against ischemic pressure. Our findings support the evaluation of rhEPO and/or its non-hematopoietic analogs in preventing to prevent PUs in patients with SFN.

Small-fiber degeneration in alcohol-related peripheral neuropathy.

BACKGROUND: Alcohol-related peripheral neuropathy (ALN) is generally characterized as an axonal large-fiber polyneuropathy caused by thiamine deficiency. We hypothesized, based on clinical observations, that ALN is associated with a small-fiber polyneuropathy that can be diagnosed with skin biopsy in heavy alcohol drinking subjects with normal thiamine status. METHODS: Eighteen individuals (9 heavy alcohol drinking subjects and 9 healthy control subjects) were assessed for the potential utility of skin biopsies in detecting ALN-associated small nerve fiber degeneration. Heavy drinking was defined as greater than 4 drinks/d and 5 drinks/d in women and men, respectively, as determined by the Timeline Follow-Back and lifetime drinking history. All subjects underwent neurological examination, nerve conduction studies, and skin biopsies to quantify end nerve fiber densities (ENFD). Other causes of neuropathy were excluded and thiamine status was assessed. RESULTS: Average ENFD were significantly decreased at the calf in the alcohol group as compared with control group (p < 0.0001). Histological sections demonstrated striking attrition and architectural simplification of intraepidermal nerve fibers in the heavy alcohol drinking subjects. There were no significant intergroup differences with respect to clinical assessments of neuropathy or thiamine status. CONCLUSIONS: ALN is associated with a small-fiber neuropathy that can be detected with skin biopsy in heavy alcohol drinking individuals with normal thiamine status. Skin biopsy is a useful, minimally invasive biomarker that could extend studies to understand the effect of alcohol on the peripheral nerves and to evaluate potential therapeutic agents in larger clinical trials.

Verapamil-induced erythermalgia.

Erythermalgia is a rare clinical syndrome characterised by intermittent, usually symmetrical burning pain, warmth and dermal erythema of the extremities with an amelioration of discomfort by cooling of the extremity. In this report, we describe a patient with erythermalgia caused by long-term verapamil use. After discontinuing the verapamil, the symptoms improved dramatically within two weeks.

Acute neuropathy and erythromelalgia following topical exposure to isopropanol.

Adverse effects resulting from topical exposure to isopropanol appears exceptional in adults with intact skin. We describe the case of a young woman who developed an acute sensori-motor axonal polyneuropathy after walking bare-feet for several hours on carpets soaked by a disinfectant containing isopropanolol. The persistence and severity of symptoms raised the possibility of her neuropathy being partly related to immunizations she received 1 mo earlier. The occurrence shortly after contact, however, strongly suggested responsibility of the dermal isopropanol exposure. This case being, to our knowledge, the second reported, peripheral nerve toxicity appears possible in adults on prolonged topical exposure, probably in susceptible individuals.

Erythromelalgia and mushroom poisoning.

OBJECTIVE: To report the first European observations of erythromelalgia due to mushroom poisoning. METHODS: Clinical features of erythromelalgia were observed in 7 cases seen over 3 years. All patients had eaten the same mushrooms species, gathered in the same French alpine valley. Erythromelalgia was first described in Japan after Clitocybe acromelalga ingestion. Clitocybe amoenolens was identified as the possible cause of poisoning in our cases.

Possible erythromelalgia-like syndrome associated with nifedipine in a patient with Raynaud's phenomenon.

OBJECTIVE: To describe a patient who was diagnosed with Raynaud's phenomenon, was prescribed immediate-release nifedipine, and developed a possible erythromelalgia-like syndrome. CASE SUMMARY: A 24-year-old white woman with a history of esophageal spasms and Raynaud's phenomenon was prescribed nifedipine 10 mg po qid. Approximately 1 hour after the patient had taken the fourth dose of nifedipine, she experienced acute erythema and a burning sensation in her feet and lower limbs, light-headedness, and palpitations. Because of a reportedly abnormally low blood pressure, the patient took diphenhydramine 50 mg po and proceeded to the clinic. On arrival, abnormal vital signs were BP 140/48 mm Hg and HR 130 beats/min. Without any other medical intervention, approximately 30 minutes later her blood pressure and heart rate had returned to baseline at 122/60 mm Hg and 96 beats/min, respectively. The nifedipine was permanently discontinued and the patient's symptoms completely resolved over 24 hours. DISCUSSION: The characteristic symptoms of erythromelalgia include burning pain, increased skin temperature, and erythema of the extremities, usually to the feet, lower legs, and, less often, the hands. Erythromelalgia-like syndromes secondary to the administration of many medications have been reported. Several nifedipine-related reports describe an erythromelalgia-like syndrome similar to our reported case. CONCLUSIONS: Because the patient was not taking any other medications and the symptoms started with the administration of nifedipine and were relieved after its discontinuation, nifedipine was thought to be the cause of the erythromelalgia-like syndrome.

[Erythromelalgia: a familial case. Discussion on the role of mercury]. / Erythromélalgie: une observation familiale. Discussion sur le rôle du mercure.

Erythromelalgia is an acrosyndrome characterized by paroxysmal manifestations associating erythema, local sensations of warmth and pain which improve with exposure to cold. Childhood forms, exceptional and usually primary, are quite severe and particularly resistant to treatment. The search for a causal agent is most often negative and the pathogenesis remains to be determined. We report a case of erythromelalgia observed in a 4-year-old girl, her father and her younger sister. This case was particular due to an association with mercury poisoning. The symptomatology was improved after different therapeutic attempts including Clomipramide and, particularly effective, rerigerating socks (D(r) Comet, CNES, Toulouse). In the literature we were unable to find any case of erythromelalgia related to mercury poisoning. The cases of familial erythromelalgia reported suggest X-linked dominant transmission. Finally, this case demonstrated the difficulties in diagnosing and treating erythromelalgia, especially in the child.

Verapamil-induced secondary erythermalgia.

A 59-year-old man developed red, swollen and warm feet accompanied by intermittent burning pain during treatment for cardiac failure and arrhythmias with several drugs including verapamil. The condition gradually worsened until there was persistent disabling burning pain and severe erythema and swelling of the feet. Aspirin and other analgesics were ineffective in relieving the discomfort. Histopathology of punch biopsies showed a mild perivascular mononuclear infiltrate and moderate perivascular oedema. Within 2 weeks of stopping verapamil the burning pain, erythema, and swelling of the feet had resolved. The clinical features and subsequent course are consistent with a diagnosis of erythermalgia secondary to verapamil.