DEFINITION
Podoconiosis or endemic non-filarial elephantiasis is a tropical non-infectious geochemical disease caused by exposure of bare feet to irritant alkaline clay soils. It is barely recognized, but widespread in many poor countries of Africa, India, Central and South America. In endemic areas, Podoconiosis is a serious public health problem: it mainly affects young active people, so social stigmatization and disability implies enormous economic losses. In February 2011 the WHO designated Podoconiosis as one of the twenty neglected tropical disease. It is unique in being an entirely preventable, non- communicable tropical disease with potential of eradication.
(Podoconiosis, a neglected tropical disease, 2012)
MeSH:
HISTORY
In the eighteenth and nineteenth centuries, the pathogenesis of elephantiasis was gradually elucidated through studies of the lymphatic system in affected people and of the role of filarial parasites. Towards the end of the nineteen century, the discrepancy between distribution of elephantiasis and distribution of filarial in Africa, Central America and Europe, prompted revision of this theory. Robles’ studies in Guatemala led to infer a linkage between some cases of elephantiasis and walking barefoot. The work of Oomen and Price in 1960-70 was important to obtain information about epidemiology, aetiology, pathology and natural history of non-filarial elephantiasis. Price, in 1988, also introduced the term ‘Podoconiosis’ from the Greek podos (= foot) and konos (=dust).
(Podoconiosis: non-infectious geochemical elephantiasis, 2007)
EPIDEMIOLOGY
It is estimated that 4 million people are affected by Podoconiosis worldwide, and 5 to 10% of the population in endemic areas where the use of footwear is uncommon. In this areas it can be even more prevalent than HIV/AIDS, tuberculosis or malaria.
It is found in highland areas (>1500 mt altitude) of tropical Africa, Central and South America and north-west India.
High prevalence has been documented in Ethiopia, Tanzania, Kenya, Uganda, Rwanda, Burundi, Sudan, Cameroon and Equatorial Guinea. The total number of cases seems to be highest in Ethiopia, in which 11 million people (almost 18% of population) are at risk through exposure of the irritant soils and estimates suggest that between 500.000 and 1 million people are affected countrywide.
Men and woman are usually equally affected. All of the major community-based studies have shown onset of symptoms in the first or second decade and a progressive increase in Podoconiosis prevalence up to the sixth decade.
(Podoconiosis, a neglected tropical disease, 2012)
(WHO | Podoconiosis: endemic non-filarial elephantiasis)
SYMPTOMS
Podoconiosis is characterized by a prodromal phase before elephantiasis sets in. Early symptoms commonly include itching of the skin of the forefoot and a burning sensation in the foot and lower leg, especially after periods of intense physical activity. Early changes that may be observed are splaying of the forefoot, plantar oedema, increased skin markings, hyperkeratosis with the formation of moss-like papillomata, and ‘block’ (rigid) toes. In local communities, it is often called ‘mossy foot disease’, because the skin becomes rough and bumpy and it seems like moss. Later, the swelling may be one of two types: soft and fluid ( ‘water-bag’ type); or hard and fibrotic ( ‘leathery’ type), often associated with multiple hard skin nodules. Very long-standing disease is associated with fusion of the interdigital spaces and ankylosis of the interphalangeal or ankle joints. Acute episodes can occur: the patient is pyrexial and the limb is warm and painful. These episodes appear to be related to super-infection and acute adenolymphangitis, and they lead to progression to the hard, fibrotic leg.
(Podoconiosis: non-infectious geochemical elephantiasis, 2007)
(Modelling environmental factors correlated with podoconiosis: a geospatial study of non-filarial elephantiasis, 2014)
DIAGNOSIS
Podoconiosis must be distinguished from filarial and leprotic lymphoedema.
- Clinical features of podoconiosis that help distinguish it from filarial elephantiasis include:
- the foot is the site of first symptoms, rather than elsewhere in the leg;
- oedema is bilateral but asymmetric, usually confined to the lower leg, compared to the predominantly unilateral swelling extending above the knee in filariasis;
- Groin involvement in podoconiosis is extremely rare.
- It occurs at altitudes higher than 1500m , which exceeds that at which filarial transmission occurs.
If doubt remains blood tests, such as midnight blood sampling and filariasis in vitro immunodiagnostic assay for the detection of Wucheria bancrofti antigen, can be used to rapidly distinguish Podoconiosis from filariasis.
- Podoconiosis may be distinguished from leprosy lymphoedema by the preservation of sensation in the toes and forefoot, the lack of trophic ulcers, thickened nerves or hand involvement.
(Podoconiosis, a neglected tropical disease, 2012)
(Podoconiosis: non-infectious geochemical elephantiasis, 2007)
PATHOGENESIS
The pathogenesis of podoconiosis is not yet fully elucidated. At present, most evidence suggests an important role for mineral particles on a background of genetic susceptibility, but the possible role of other cofactors (for example chronic infection or micronutrient deficiencies) has not been explored.
- Mineral particles: Robles and Price’s studies evidenced a link between Podoconiosis and red clays, rich in alkali metals and associated with volcanic activity. The climatic factors necessary for producing irritant clays include: high altitude (over 1500 m above sea level), seasonal rainfall (over 1500 mm annual rainfall) and land surface temperature mean annual of 19-21 °C. These conditions contribute to the steady disintegration of lava and the reconstitution of the mineral components into silicate clays; in particular smectite, mica and quartz are related with Podoconiosis. The correlation between podoconiosis and smectite was larger than that between podoconiosis and other phyllosilicate minerals or quartz: it has the ability to adhere to the skin and form a protective film and absorbe water. These properties might potentially, through establishment of an external water gradient influencing permeability of the stratum corneum, increase transdermal uptake of potential toxins and colloid-sized particles of elements common in irritant clays (aluminium, silicon, magnesium and iron). These particles have been demonstrated in the lower limb lymph node macrophages of those living barefoot on the clays; electron microscopy shows local macrophage phagosomes to contain particles of stacked kaolinite ( Al2Si2O54 ), while light microscopy shows subendothelial oedema and subsequent collagenization of afferent lymphatics reducing and finally obliterating the lumen. A study about the role of inflammatory biomarkers shows an increasing of reactive oxygen species ( ROS ). In addition to oxidative stress-related mechanisms there is some evidence for a role of transforming growth factor ( TGF-b1 ) in mediating ultrafine particle damage. The effects of TGF-b1 are diverse and include the modulation of cell proliferation and differentiation, angiogenesis, inflammatory or immune responsiveness, and induction of extracellular matrix production. In podoconiosis there is a reduction of TGF-b1 levels; there are several possible explanations for this reduction. Firstly, oxidative stress or cytokines released by soil components may lead to inhibition of one of the signaling pathways controlling the expression of TGF-b1. Secondly, chronic exposure to soil particles may lead to inactivation and apoptotic death of macrophages and keratinocytes, the major sources of TGF-b1. This would be consistent with the progressive reduction in the TGF-b1 level in advanced stage disease. Thirdly, inherited polymorphisms may have led to reduction in the expression of the TGF-b1 gene.
Elevated levels of zirconium and beryllium in the soil of endemic areas suggest a role of these elements in the pathogenesis of Podoconiosis: probably they cause dryness and cracking of skin on the feet; this may facilitate the ingress of mineral particles or microorganisms through the skin barrier.
Geographic similarities of KS to podoconiosis in Africa implicate a common role of some factors in pathogenesis of KS and podoconiosis. The hypothesis of soil exposure as a risk for endemic KS has been strengthened by recent investigation. Particulate soil exposure may cause localized microtrauma and inflammation, predisposing to KS on the extremities in HHV-8 infected men. Other studies also notes volcanic soil is an indicator of high density of phlebotomes, which for some authors may represent HHV8 vectors.
- Genetics: there is familial cluster of the disease and the heritability is estimated to be 63%. Brothers and sisters of patients have a five times higher risk of developing Podoconiosis than people in general. A recent study, using a genome-wide approach, found an association of Podoconiosis with genetic variants in the HLA2 loci: HLA DQA1, DRB1 and DQB1 confer higher risk for Podoconiosis. This suggests that it may be a T-cell mediated inflammatory disease.
(Podoconiosis, a neglected tropical disease, 2012)
(Podoconiosis: non-infectious geochemical elephantiasis, C007)
(Spatial distribution of Podoconiosis in Relation to Environmental Factors in Ethiopia: A Historical Review, 2013)
(Modelling environmental factors correlated with podoconiosis: a geospatial study of non-filarial elephantiasis, 2014)
(Ten years of Podoconiosis research in Ethiopia, 2013)
(The role of transforming growth factor-b1 and oxidative stress in podoconiosis pathogenesis, 2010)
(Kaposi’s sarcoma, oncogenic viruses, and iron, 2001)
(La puntura di artropodi ematofagi quale possibile cofattore nella trasmissione di HHV8 (Human Herpes Virus 8) e nell’espressione del sarcoma di Kaposi, 2002)
PREVENTION & THERAPY
- Primary prevention consists of avoiding or minimizing exposure to irritant soils by wearing shoes or boots and by covering floor surfaces inside traditional huts. The Mossy Foot Prevention and Treatment Association trains treated patients to make low-cost durable leather boots and shoes for their communities; in Kenya, sandals are made from old car tyres with a similar aim. However, footwear remains an unaffordable luxury for residents of most affected areas in the tropics.
- Secondary prevention involves training in a simple lymphedema treatment regimen, similar to that used in management of filarial lymphoedema. The regimen includes daily foot-washing with soap, water and antiseptic, use of a simple emollient, bandaging in selected patients, elevation of the leg, controlled exercises, and use of socks and shoes. Compression bandaging is highly effective in reducing the size of the soft type of swelling.
- Tertiary prevention encompasses secondary prevention measures, elevation and compression of the affected leg, and, in selected cases, removal of prominent nodules. For elevation to be successful, at least 18 hours with the legs at or above the level of the heart are needed each day. More radical surgery (Charles’ operation: removal of skin, subcutaneous tissue and deep fascia to lay the muscles and tendons bare, followed by grafting of healthy skin) is no longer recommended since patients unable to scrupulously avoid contact with soil experience recurrent swelling which is more painful than the original disease because of scarring. Social rehabilitation is vital, and includes training treated patients in skills that enable them to generate income without contact with irritant soil. Successful training in shoemaking, bicycle repair, hairdressing and beauty care, electronics and carpentry has been given to several hundred treated patients by the Mossy Foot Association in southern Ethiopia.
(Podoconiosis: non-infectious geochemical elephantiasis, 2007)
(WHO | Podoconiosis: endemic non-filarial elephantiasis)
IMPLICATIONS
Podoconiosis has enormous social, psychological and economic implications for affected individuals. Social stigmatisation of people with the disease is widespread and patients are banned from schools, local meetings, churches and mosques, and not allowed to marry into unaffected families. Price (1974) reports that one podoconiosis sufferer remarked ‘it would be better to have leprosy’, since stigma surrounding leprosy has diminished as a consequence of effective medicine and health care services. The belief that there is no effective medical treatment may act as a barrier to accessing health care. Recent evidence suggests that sufferers attempting to access non-specialist health services encounter lack of expertise and prejudicial attitudes among health workers. Furthermore, around half incorrectly considers Podoconiosis to be an infectious disease and are afraid of acquiring it while providing care.
Therefore, podoconiosis threatens economic development because it mainly affects the most productive people (16 to 45 years of age), sustaining the disease-poverty cycle. Research has demonstrated a loss of productivity equivalent to 45% of working days per patient annually. This costs a single zone of 1.5 million inhabitants more than US$ 16 million per year; the annual economic losses for Ethiopia are estimated to exceed US$ 200 million in lost productivity and medical costs.
(Podoconiosis, a neglected tropical disease, 2012)
(Podoconiosis: non-infectious geochemical elephantiasis, 2007)
Angilletta Roberto
Di Tria Roberta
