Iron therapy in hand eczema: a new approach for management.

It is observed that adequate iron intake and status can limit nickel absorption from the diet in the human body. Chronic vesicular hand eczema (CVHE) due to nickel sensitivity is a common dermatological condition where the dietary nickel acts as a provocating factor. Such patients are usually treated with low nickel diet (LND). The present study was conducted to observe the result of addition of oral iron with LND in the treatment of CVHE in patients due to nickel sensitivity. 23 patients with CVHE due to nickel sensitivity were taken for this study. Study group (12 patients) were advised LND with oral iron for a period of 12 weeks. Control group (11 patients) were advised LND alone for a period of 12 weeks. Fast improvement noted in the skin lesions of the study group patients; 10 (83.33%) patients had complete clearance of their hand eczemas at the end of 12 weeks. There were significant reductions in the blood level of nickel in those patients. Moderate improvement noted in the skin lesions of the control group patients; 5 (45.45%) patients showed complete clearance of hand eczema at the end of 12 weeks. This study showed that oral iron helped to reduce nickel absorption from the diet. The study also showed that combination of LND and oral iron can bring a faster reduction in the severity of clinical symptoms of CVHE in a nickel sensitive individual.

Introduction

Chronic vesicular hand eczema (CVHE) due to nickel sensitivity is a common dermatological condition. It is a chronic and recurring disease. In this condition, the dietary nickel acts as a provocating factor. Diet rich in nickel tend to aggravate the condition of hand eczema; the reverse happens with the diet low in nickel. One of the methods of treating such VHE is low nickel diet (LND). The purpose of such diet is to reduce the uptake of nickel by the body from the diet. Careful selection of food with relatively low nickel concentration can bring a reduction in the total dietary intake of nickel per day and thereby can minimize the risk for endogenous activation of immunocompetent cells in nickel sensitive individuals. This can influence the outcome of the disease and can benefit the nickel sensitive patient. However, it is important to note that nickel content of the same foods varies from place to place and even in different batches of the same food. Even seasons can influence the concentration of nickel in food.[1] Therefore the benefit received by a patient from a particular LND may not be uniform in all patients. It is always a difficult task for the clinician to draft an LND which is effective for all patients working for all the seasons due to the variation in the nickel content in the food. It is not possible also to measure precisely the nickel content of every food. Fortunately it has been observed that adequate iron intake in the food can limit nickel absorption from the diet. In other words, by adding iron to diet, dietary uptake of nickel by human body can be reduced significantly. This is due to the down regulation of divalent metal transporter molecule on the luminal surface of enterocyte.[2]

The present study was conducted to observe the result of addition of oral iron with LND in the treatment of CVHE in patients due to nickel sensitivity.

Materials and Methods

All total 23 patients (male: 8 and female: 15) with CVHE due to nickel allergy were included for this study. All these cases were subjected to thorough history taking, clinical examination, complete blood investigation and patch testing using Indian Standard Battery of Allergens approved by CODFI. In all th se patients, oral challenge with nickel sulfate was done to confirm the diagnoses of nickel allergy.

The youngest patient was 18 years old and the oldest patient was 35 years old. Following group of patients were not included in the study: patient with atopic diathesis, patients with anemia, patient with history of recurrent bleeding gum, patient with history of hematemesis and melena, patient with history of bleeding per anum, patient with history of menorrhagia, patient with abnormal blood picture, patients who were using prosthesis e.g., orthodontic appliance, intra-modularly nail etc., pregnant female and lactating mother. In each patient, stool examination was done for occult blood and worm infestation, especially hookworm infestation. Urine test was done to exclude hematuria. Both verbal and written consent was taken from each of the patient.

All the 23 patients were randomly divided into two groups: Study (12 patients) and Control (11 patients). Duration of study period was 12 weeks. All these 23 patients were given a list of dietary items that contains low amount of nickel. They were instructed to stick to these items till the end of the study. This list was prepared considering the food habit of the local community and convenience of the participants. Patients in study group were advised to take oral iron daily in a dose of 30 mg of elemental iron (15mg just before lunch and 15mg just before dinner) daily, which is the recommended daily dietary requirement for Indian people. Hemoglobin levels were re-evaluated at 12-week interval in study group.

Low nickel diet advised was as follows:

Foods with no restriction – Milk, Food prepared from Wheat flour, Food prepared from polished rice, Cornflakes, Egg, Rice (Polished), Cottage cheese, Fish, Meat, Potatoes, Cabbage, Cucumber

Foods with restriction – Onion and garlic in moderation, Fruits (Banana, ripe:3–4 times a week, Apple:3-4 times a week); Tea, not very strong, 1–2 times a day. For cooking, Mustard oil, Salt, Sugar, Turmeric powder (in moderation), pepper allowed.

Patients with infected hand eczema were first treated with oral and topical antibiotic prior to the initiation of trial. Patients of either group were allowed to apply petroleum jelly topically during the treatment period. No patient was allowed to use steroid (both topical and oral) and other immunosuppressive during this period. The severity of hand eczema was measured by using Severity Parameters and Scores for Hand Eczema. Each patient was assessed at 4-week intervals and the severity scores were calculated and documented [Table 1].

Table 1

Severity parameters and scores for hand eczema

Results

In the study group

There was rapid improvement in the skin lesions of the participants observed at the end of 4 weeks in all patients; a >50% reduction in skin lesions noted. All the skin symptoms were reduced significantly, which was reflected in the hand eczema severity scores.

Seven patients showed complete clearance of hand eczema by the end of 8 weeks. They did not experience any relapse till the end of 12 weeks.

All total 10 out of 12 patients (83.3%) in the study group had complete clearance of their hand eczema at the end of 12 weeks [Figures 1 and 2].

Figure 1

Patient 2: Before treatment, SG

Figure 2

Patient 2: After treatment, SG

Only 2 patients continued to suffer from mild recurrence [Table 2].

Table 2

Result of study group

There were significant falls of blood nickel levels in all of these patients.

In the control group

There was mild improvement in the skin lesions of the participants observed at the end of 4 weeks in all patients.

By the end of 8 weeks, all the skin symptoms were reduced significantly in all 10 patients; a >50% reduction in skin lesions noted which is reflected in the hand eczema severity scores [Figures 3 and 4].

Figure 3

Patient 1: Before treatment, CG

Figure 4

Patient 1: After treatment, CG

Five patients (45.45%) showed complete clearance of hand eczema at the end of 12 weeks [Table 3].

Table 3

Result of control group

Remaining patients continued to suffer from recurrence.

There were moderate falls of blood nickel levels in the control group patients.

Discussion

Iron is mostly absorbed from the proximal part of small intestine in the human body. In the intestine, except haem-iron, all other forms of dietary iron are transported into the enterocyte of intestinal epithelium by a divalent metal transport protein, which is known as divalent metal transporter (DMT); also known as divalent cation transporter. Divalent metal transporter is a 561-amino-acid protein with 12 putative membrane-spanning domains and is ubiquitously expressed, most notably in the proximal duodenum. Divalent metal transporter is a key mediator of intestinal iron absorption and a member of the ‘natural-resistance-associated macrophage protein’ (NRAMP) family. Once iron is bound to DMT on the luminal surface of enterocyte, it is transported across the membrane for the utilization in the body. However, DMT molecule can transport not only ferrous iron; in absence or paucity of iron they can transport other divalent metals.[34] The DMT's preference in order of affinity is Fe2+>Zn2+>Mn2+>Co2+>Cd2+>Cu2+>Ni2+>Pb2+. However, higher concentration of any of these metals can interfere with this order.[5] Gunshin et al,[4] found that DMT molecules are up-regulated by dietary iron deficiency. It is seen that patients with iron deficiency expresses more DMT molecules on the luminal surface of enterocytes than the normal individual in order to absorb more iron.[6] When the diet is low in iron, the DMT molecules on the surface of enterocytes tend to bind and transport immediately available other divalent cation(s) including nickel across the membrane in higher amount. This is very important for those suffering from nickel allergy; because nickel is a ubiquitous trace element and it is present in most of the human foods. In other words, such individual are at higher risk to accumulate nickel in their body. However, it has also been found that adequate iron intake and status can limit nickel absorption due to the down-regulation of DMT molecule on the luminal surface of enterocyte.

In this present study, effort was made to reduce the severity of clinical symptoms as well as the recurrence rate of hand eczema in nickel sensitive individuals by promoting oral iron therapy with LND to the patients. The purpose of adding oral iron was to ensure adequate iron in the diet and thereby to reduce the uptake of nickel by the body from the diet and thereby to minimize the risk for endogenous activation of immunocompetent cells in nickel sensitive individuals. Result observed in the study group showed the benefit of oral iron therapy along with LND. The treatment was well tolerated by the patients. Differences in result of two groups are statistically significant (unpaired t-test).

Conclusion

This study showed that oral iron helped to reduce nickel absorption from the diet. The study also showed that combination of LND and oral iron can bring a faster reduction in the severity of clinical symptoms of CVHE in a nickel sensitive individual.

However, the present study is a clinic-based study and the study group was small. A further multicentric study comprising of large number of patients with longer follow-up will be more informative.