Hookworm-related cutaneous larva migrans (CLM) is a parasitic skin disease caused by the migration of animal hookworm larvae such as Ancylostoma braziliense, A. caninum or Uncinaria stenocephala in the epidermis. The infection occurs when third-stage larvae come into contact with human skin and penetrate into the epidermis. Since animal hookworm larvae cannot penetrate the basal membrane of the human host, they remain confined to the epidermis where they migrate for several weeks or months, and eventually die in situ [1]. CLM is frequent in impoverished rural and urban communities in countries with hot climates [2], [3], [4], [5], [6]. In these settings the prevalence of CLM can reach 4% in the general population and 15% in children <4 years. [6], [7], [8]. CLM belongs to the category of neglected tropical diseases [9], [10].

The main symptom of CLM is severe pruritus, which intensifies at night. The itching leads to sleep disturbance and day somnolence [6]. Scratching may cause extensive excoriations and subsequent bacterial superinfection of the lesions, typically by Streptococcus pyogenes or Staphylococcus aureus. Bacterial superinfection by group-A streptococci may induce the development of post-streptococcal glomerulonephritis [11].

A recent study on knowledge, attitudes and practice among mothers of children with CLM highlighted the psychosocial stress associated with this parasitic skin disease and its negative impact on family life (H.Lesshafft 2010, unpublished data). This prompted us to investigate the impairment of skin disease-associated life quality in patients with CLM in a semi-quantitative manner.

Ninety-one patients were included in the study, 63 of them were male and 28 female. The median age was 10 years (IQR 7-12, range 5–44 years). The demographic and clinical characteristics of the patients are summarized in Table 2. Forty-four point eight percent of the patients had more than two lesions. The maximal number of lesions was 51. 88% of the patients had noted the appearance of the oldest track during the last four weeks. Figure 1 shows a typical example of an inflamed and superinfected track at a visible body part.

Nearly all study participants showed a reduction of life quality (mDLQI≥2 points) at the time of diagnosis (Table 3). The majority of the patients (51.6%) showed a moderate life quality impairment.

At baseline, the median mDLQI score was 5 (IQR 3-8). 6 (IQR 3-9) for adults and 5 (IQR 3-8) for children (p = 0.7; Table 4). Pruritus, sleep disturbance, feeling of shame and the need to dress differently were the most frequent restrictions. Significant differences in perceived restrictions between adult and child patients existed for problems faced at work/school and impairment in social relationships (p = 0.040 and p = 0.026, respectively). There was no difference in mDLQI scores between boys and girls (5 [IQR 3-8] versus 6 [IQR 3-7]; p = 0.86) and men and women (6 [IQR 3.-9] versus 4 [IQR 2-9]; p = 0.63).

The degree of skin disease-associated life quality impairment correlated strongly with the severity of the infection (rho = 0.76; p<0.001) (Figure 2) and the number of affected body areas (rho = 0.30; p = 0.004) (Figure 3). A significant correlation existed between the presence of lesions in clearly visible body areas and the mDQLI score (p = 0.002).Skin disease-associated life quality impairment did not depend on the number of CLM episodes experienced previously (p = 0.88), the duration of the infection (p = 0.52), or the presence or absence of bacterial superinfection (p = 0.80).

The follow–up examinations showed an improvement of skin disease-associated life quality two weeks after treatment with ivermectin (median mDLQI = 5 [IQR 3-8] versus 1 [IQR 0-3; p<0.001] Table 5). Four weeks after treatment, the median mDLQI score was zero and 82% of the patients reported a normalization of their skin disease-associated life quality. The normalization of skin disease-associated life quality was paralleled by a drastic reduction of the CLM severity score from a median of 4 points (IQR 3-6) to 1 point (IQR 1-1) two weeks after treatment with ivermectin and to 1 point (IQR 0-1) at the end of the study (both p<0.001). Figures 4 and 5 show the resolution of the inflammatory skin reactions around embedded hookworm larvae before and four weeks after treatment with ivermectin.

Diseases of the skin lead to various levels of suffering. First, they cause defined clinical pathology, such as visible inflammation, pruritus or pain. Second, skin diseases are frequently chronic in nature and patients have to take drugs, either topically or orally, for a protracted period of time. Third, if gross alterations of the skin are located on visible body parts, they may, at worst, lead to social withdrawal and/or to exclusion from society, as it is the case, for instance, with leprosy [21]. Additionally, patients may be confronted with ignorance or misconceptions regarding the aetiology of their skin disease, such as the fear that the condition is contagious or related to poor personal hygiene – assumptions which may lead to stigmatisation [22], [23]. Lymphatic filariasis with gross lymphoedema is a paradigmatic example of this category of skin diseases [24], [25], [26].

CLM is an extremely itchy skin condition characterized by signs of inflammationm such as erythema. Since lesions are frequently located at visible body parts they are difficult to hide from the public [13] and negative impact on emotional well-being of the patient is possible..In our study 94.5% of patients with CLM reported reduction of their skin disease-associated life quality with a median mDLQI score of 5 (Table 3). The degree of skin disease-associated life quality impairment was positively correlated with the intensity of the infection (Figure 2), the number of body areas affected (Figure 3), and the presence of lesions at clearly visible body parts.

In contrast to a study in patients with scabies [20] we did not find different degrees of impairment between women and men. This could be due to the fact that scabies lesions usually are less obvious to the patient and external observers/third parties than highly inflamed larval tracks. Besides, in scabies the lesions are frequently located at “hidden” topographic areas, such as the interdigital spaces. Finally, the preponderance of male participants in the study – a consequence of the higher prevalence of CLM in males in the area where the study was conducted – may have blurred the differences between the sexes.

The most common finding associated with an impairment of skin disease-associated life quality was pruritus (93.4% of the patients). Pruritus causes the patient to scratch repeatedly- a behavior which does not pass unnoted by other members of society [27]. In addition, since the intensity of itching increases at night, it causes alterations in the sleep pattern. The affective aspect of pruritus may induce a vicious cycle in which increasing mental harm and distress lead to increased itching which, in turn, augments scratching [27], [28].

Insomnia was reported as a cause of life quality impairment by 73.6% of the patients. A previous study has shown that CLM related insomnia manifests itself as a sleep maintenance disorder [13], probably due to an increased perception of pruritus during the night. In patients with pruritus-induced perturbation of sleep, quality and duration of sleep are reduced as a consequence of shorter non-REM sleeping periods [29]. This may cause daytime somnolence, irritability and psychological problems such as anxiety disorders [30], [31].

It seems paradoxical that insomnia has been cited as most important restriction by people living in an invasão. From an outside observer's point of view, getting rest and sleep in this setting seems to be very difficult anyway: poor housing and a high population density allow noise to enter the house almost unaltered and loud music is heard even late at night. However, our patients seem to have adapted to the extremely noisy environment of an invasão and considered sleep and recreation to be severely impaired by the CLM-related pruritus. In fact, after treatment, insomnia was reduced significantly already after two weeks (Table 3).

The feeling of shame was noted by 64.8% of the patients. In our study on knowledge, attitudes and disease perception, it was found that shame frequently resulted from the concept that the occurrence of CLM reflects poor personal hygiene and lack of care (H. Lesshafft, unpublished observation).

Another commonly noted restriction is related to the necessity of patients with CLM to dress differently. In the hot climate of northern Brazil a great part of the body remains uncovered. Hence, skin lesions are difficult to hide and the effort to cover them up with extra clothes or bandages may lead to a reduction of self-esteem and provoke shame and stigmatisation [23], [32], [33]. These somato-psychological interactions were confirmed by our finding that mDLQI scores were highest in patients in whom lesions were present at clearly visible parts of the body.

Problems faced at work or at school and impairment of personal relationships were also a frequently noted restriction of skin disease-associated life quality (Table 4). Several mechanisms may underlie these psycho-social consequences. First, and similarly to other skin diseases such as psoriasis, the erroneous assumption that CLM is contagious leads to alterations in personal relationships and eventually to social exclusion [23]. Second, as shown in a previous focus group discussion in the study area (unpublished data), mothers frequently ban affected children from playing outside, partly to prevent a new infection and partly to avoid teasing by other children, which may cause boredom and or lead to a feeling of social exclusion. Thirdly, bullying and interrupted personal relationships may provoke a feeling of disgust and shame about the skin condition and reinforce an active withdrawal from social networks due to the fear of stigmatisation [23], [22].

With regard to personal relationships, the significantly lower impairment of skin disease-associated life quality in children compared to adults might be explained by the fact that consciousness about their own appearance interferes less in children's relationships. The higher impairment perceived by adults at work is presumably related to a similar mechanism. At work, adults are confronted with the “outside world” in which CLM reflects a life in poverty. In contrast, children - going to school in the community - do not leave their social environment and consequently may perceive less life quality impairment.

Hitherto, only a few studies have attempted to determine skin disease-associated life quality impairment in tropical parasitic skin diseases.

While in patients with active cutaneous leishmaniasis or onchocerciasis, the average impairment was found to be higher than in the CLM patients of our study, skin disease-associated life quality restrictions in lymphatic filariasis caused a similar or higher impairment depending on the severity of lymphoedema [24], [25], [26], [32], [33], [34]. In contrast, patients with scabies living in an invasão in Northeast Brazil percieved less impairment than our patients with CLM [20]. In scabies the duration of infection, but not the number of infested body areas, correlated with skin disease-associated life quality impairment. This is probably due to the rather slow development of the clinical pathology in scabies, where the degree of skin alteration increases gradually, whereas in CLM inflammatory skin reactions develop within a couple of days.

We think that our data clearly indicate a cause-effect relationship between cutaneous larva migrans and impaired quality of life. First, the severity of disease was significantly correlated to the degree of impaired quality of life (rho = 0.76; p<0.001) and number of body areas affected (rho = 0.30; p = 0.004), indicating positive “dose-response” relationships. Second, already two weeks after the regression of skin lesions due to treatment with ivermectin, the degree of life quality impairment decreased significantly. Taken together, these findings provide substantial evidence that the impairment of life quality is the consequence of the parasitic skin disease as it has been observed in patients suffering from other parasitic infections [24]–[26] [32]–[34]. These findings also suggest that a treatment that costs approximately 40–80 eurocents, not only abrogates clinical pathology, but also averts stressful psycho-social consequences and prevents the development of secondary morbidity when given promptly.

When interpreting our results one has to take into account that skin disease-associated life quality of people living in misery in an urban slum is very low per se [35]. Housing is poor, sanitary infrastructure is deficient, crowding is common and social problems such as unemployment, alcoholism, illiteracy, and violence prevail. Obviously, these characteristics should mitigate perceived restrictions on skin disease-associated life quality in our patients. In fact, the results of another study in the same setting showed that members of the community considered parasitic skin diseases negligible in comparison to the existential problems of daily life (H. Lesshafft, unpublished observation).

In conclusion, CLM impairs the physical and mental wellbeing as well as social interaction of patients in a setting where skin disease-associated life quality is generally low. A single dose of ivermectin caused a complete resolution of the lesions within one month and restored skin disease-associated life quality to the normal level.