Tropical phagedenic ulcers

What we call tropical ulcers today are a distinct entity also known as tropical phagedenic ulcers. Phagedenic refers to its appearance as if it was gnawed. These are painful, rapidly enlarging sores, usually found on the lower limb in individuals living in a hot, humid tropical region. Young children are affected more frequently. In adults, they occur more often in women than in men.

 

Synonyms are Vincent's ulcer; jungle rot; Naga sore; tropical sloughing phagedena; ulcus tropicum, malignant ulcer, putrid ulcer, Cullen ulcer,  gangrenous ulcer, phagedena gangrenosa, phagedena  ("eating away"), progressive synergistic bacterial gangrene, acute dermal gangrene, and acute synergistic gangrene.

What is the cause of a tropical ulcer?

Multiple factors play a role in causing tropical ulcers. The majority of tropical ulcers occur below the knee, primarily on the anterolateral aspects of the lower limbs and commonly around the ankle.

  • Initially, there is some form of trauma/injury to the skin, often as minor as a scratch or an insect bite. Rural labourers who do not wear adequate protective clothing and footwear are at increased risk. Minor skin wounds allow penetration of the organisms present in mud or stagnant water and are thought to release toxins that cause a necrotic reaction in dermal tissue and lead to skin breakdown.

  • Poor nutrition, poor hygiene, and chronic diseases such as malaria and intestinal parasites also increase the risk of a tropical ulcer developing.

  • A variety of bacteria are found to be present; Fusobacterium species are almost always present in the early stages; Bacillus fusiformis and Treponema vincenti are often found in the late stages. Other bacteria such as Escherichia coli and Enterococcus species may be present. The threshold for ulceration is considerably lowered when polymicrobial infections are present. In other words – when several species of bacteria infect the wound area simultaneously, this leads to a more rapid breakdown of tissue.

Clinical features of a tropical ulcer

Usually, a small discoloured patch on the lower leg develops rapidly over 5-6 days into a pustule of more than 1cm. When the pustule ruptures, foul-smelling blood-stained pus exudes. Considerable tissue damage is apparent at this stage as full-thickness epidermal tissue has been destroyed to reveal an ulcer.

 

The ulcer is regular round/oval in shape, with a sloughy wound bed and a somewhat defined but often irregular edge. The edge will not be significantly undermined as opposed to, for example, Buruli ulcer, where undermining is very typical. The ulcer can be very deep, going beyond muscle tissue down to exposed tendons or periosteum, although bone infection is not so common.

Oedema exists around the ulcer and hyperpigmentation, which can last a significant amount of time after the ulcer has healed.

Generally, the ulcer increases in size during the first 2-3 weeks (the acute phase) and the maximum size is reached at around six weeks. It is typical for the ulcers to be filled with wet, gangrenous slough. After weeks of autolytic debridement, the wound bed will usually show more granulation tissue, but often it remains in this chronic granulation phase. Initially, in the acute phase, the wound will be very painful. If the wound does not heal and moves into a chronic phase, the pain gradually diminishes and can become completely absent. 

wa tropical ulcer 2.png

Figure 1 A young boy in Northern Uganda with multiple tropical phagedenic ulcerations on both legs. These had started to go over into the chronic phase and were not as painful anymore. This image is published here courtesy of Jennifer Kragt. She reported in her blog that surprisingly many children in the Karamoja region of Uganda had one or more of these tropical ulcers. 

How is tropical phagedenic ulcer diagnosed?

This is where it gets a bit tricky because the list of possible differential diagnoses is quite lengthy and complicated. Also, to pinpoint the exact diagnosis, you need both a microbiology laboratory and a laboratory that can examine histopathological samples. Tropical phagedenic ulcers are most common in remote areas where these services are not readily available.

A few characteristics of the clinical features may help us in the right direction. T  first thing we have to think about is whether it can be a Buruli ulcer because Buruli ulcer requires specific antibiotic treatment to achieve healing. Both tropical phagedenic ulcers and Buruli ulcers are more common in children. Buruli ulcers, however, are typically more undermined. Furthermore, with Buruli ulcers, the primary lesions are usually not painful. This is the opposite with tropical phagedenic lesions, where the early lesions are generally very painful. Buruli ulcer is often concentrated in certain regions in Africa. Healthcare workers there are often trained to spot this diagnosis and will not always require bacterial swabs to make a reasonably accurate diagnosis.

Besides Buruli ulcer, you will also have to think about differential diagnoses like cutaneous diphtheria, pyogenic ecthyma, pyoderma gangrenosum, syphilitic gummata, leprosy, chromomycosis, squamous cell carcinoma, and venous disease.   The latter two diagnoses are not common in children but have to be considered when ulcerations appear in adults.

 

If you have access to microbiological swabs and a laboratory that can do a histopathological examination, you should use both sampling methods. That is, taking a bacterial swab from the cleaned wound bed - both from the center of the wound and from the wound edges ( please refer to the chapter  " taking a microbiological sample")  as well as taking multiple biopsies, especially from the edges of the ulcer, and sending them in a glass of formalin. It is essential to tell the microbiologist/pathologist as much information as possible and what differential diagnoses you are thinking about. There is no specific histological pattern for tropical phagedenic ulcers, but a tissue biopsy will help you rule out some differential diagnoses, especially malignant processes.

How is tropical phagedenic ulcer treated?

It is thought that if the early pus-filled pustules are drained initially, the deterioration process can be stopped, and the resulting ulcer will usually be much smaller in size and more manageable. Unfortunately, most patients do not seek medical help at this stage and only come to the clinics once the ulcers have become large. Educational campaigns in rural areas about this may help get patients to seek help at an earlier point in time. 

Is there a need for antibiotics?

Usually, tropical phagedenic ulcers will heal without antibiotic treatment. Systemic antibiotic therapy is warranted if there are signs of severe local infection or even systemic symptoms like high fever and general malaise. As opposed to Buruli ulcers, no clear consensus recommendation as to tropical phagedenic ulcers has been made concerning the choice of antibiotics. Most of the literature recommends penicillin, erythromycin, tetracyclines, or metronidazole as possible choices. Usually, -10 days of antibiotic treatment is sufficient. If you are unsure what antibiotics to start with, some authors recommend the following as first-line treatment:  A combination of penicillin (500mg every 6 hours for 1 week) and metronidazole ( 250mg every 8 hours for 10 days). For patients who are allergic to penicillin, tetracycline ( for example, minocycline or doxycycline 100mg twice daily) can be given instead.  

Debridement

In general, we treat these ulcers like many other chronic ulcers. If there are only moderate amounts of necrotic tissue, you may choose more conservative methods of debridement- processes that aid the autolytic debridement process. Covering the wound bed in honey and using moistened gauze dressings can be useful here. We have also used granulated sugar to debride leg ulcerations in both the acute and chronic phases. Fill the entire ulcer cavity with white granulated sugar. This works best if applied daily, as the wound exudate quickly dissolves the sugar. It is essential to have a good absorbent dressing over this, as sugar draws fluid from the wound bed and causes an increase in exudate, at least in the initial phase of the treatment. The patient must be informed that both honey and sugar can attract ants, especially during the night.   Another method of debridement is using papaya directly applied to the wound bed. Again, please refer to our chapter on debridement for more information about this and other methods. 

 

 

If there is an abundance of necrotic tissue, this will not only delay the healing of the wound but can encourage secondary infection by other bacterial strains. A careful surgical debridement of the wound may reduce the healing time and reduce the pain in the ulcer and reduce the length of the antibiotic treatment.

Since these ulcers are usually very painful, it is important to do the debridement under some form of anesthesia. In many cases, adequate debridement can be done with local anesthesia -  with, for example, lidocaine. If the lidocaine is injected slowly under the necrotic tissue, the injections can be quite painless. Some caregivers inject the local anesthesia around the edge of the ulcer- this is very painful, so we do not recommend this!

 

In ulcers with extensive necrosis and infection, a thorough debridement under sedation or even general anesthesia may have to be done, if that is available. We have written a separate chapter on debridement and refer to this. We also believe that debridement by medicinal maggots is a suitable method here- we also refer to the chapter about medicinal maggots.

What kind of topical treatments/ dressings are recommended?

 

We generally like to use antibacterial rinse solutions to irrigate the ulcers at dressing changes. It is recommended to let these substances soak into the wound for about 15-20 minutes. We usually saturate a cotton gauze pad with this ( dripping wet and lay this into the ulcer bed. Depending on what you have available, you can use a 2% vinegar solution for this, super-oxidized water, or 3% hydrogen peroxide. Remember that you can make the vinegar rinsing solution yourself.   After this rinse, we like to paint the entire wound bed with gentian violet - this normally penetrates a few millimeters into the wound's surface, and we believe it may lead to quicker eradication of bacteria. We only use the gentian violet during the first two or three dressing changes as it is unknown how beneficial ( or harmful) this substance is to healthy tissues.  

It appears that filling the wound bed with activated charcoal, especially during the initial phases, may delay further bacterial growth and probably aids in neutralizing bacterial toxins, which cause tissue destruction. You will find more about the charcoal method under " Antibacterial dressings."

Once the ulcer has " stabilized" and is not growing anymore, we can go over to more regular dressing choices. If you have few resources, cotton gauze dressings can be used. If the wound has little exudate, you can premoisten the gauze with, for example, the 2% vinegar solution ( they should only be slightly moist, not dripping wet!). You can apply a thin layer of zinc paste mixed with petrolatum jelly ( 50:50 ratio) over the entire wound bed to prevent the gauze from sticking to the wound bed, making removal painful during dressing changes. 

 

If you have access to more modern dressings, then most polyurethane foam dressings would be appropriate here, especially those with antibiotic properties like silver coatings or those containing iodine. Another excellent dern dressing for this purpose is Sorbact gauze.   Once the ulcer bed is clean from necrotic tissue and shows promising granulation tissue, negative pressure wound treatment can be applied if available.

Once the wound bed is covered in good granulation tissue, partial thick skin grafting can shorten the healing time and possibly improve the cosmetic result. Remember that there are also simpler techniques for transferring epidermal cells like the " blister technique" and punch-grafting methods. Please refer to the c apter on skin grafting for more information about these methods. However, in most rural areas, these techniques are not available, and tropical ulcers are left to heal by the natural process.

Remember, as always in wound care: nutrition plays a decisive role. Especially protein supplementation and vitamin supplements ( Vitamin C!) are advised. 

If you have the resources and facilities, get the patient hospitalized for the initial part of the treatment ( about seven days). In this way, we can better control what is going on in the wound, do careful serial debridements  (which are less painful), and frequent dressing changes. Furthermore, we can use those days to supply the patients with extra proteins and vitamins. During that time, the patient should also be taught how to change the dressing by themself or teach a caregiver.   We are, of course, aware that many rural hospitals do not have the resources to take in all patients with ulcerations, or even more commonly, that the nearest hospital is a day's travel away. In most cases in rural areas, patients will therefore need to be treated as out-patients. 

 

In summary, there are several treatment modalities you can apply here. It really depends on what you have available and your personal preferences. At the start of the treatment, it will be wise to do frequent dressing changes and gradually decrease the frequency as the wound improves. In most situations in rural areas, you cannot expect the patient to return for a new visit the next day, and we advise you to use the time to inform the patient/caretakers thoroughly and teach them how to do the dressing changes themselves. To summarize the treatment options, we have listed them here:

 

Wound irrigation: 

 

  • 2% vinegar, Super-oxidized water, or 3% hydrogen peroxide

 

Antibacterial effect:

 

  • Gentiana violet 1-2% solution applied to the entire wound bed at least during the first two dressing changes ( at least during the first treatment at your clinic)

 

Primary Wound dressings if resources are limited:

  • Honey ( applied daily until necrosis has cleared, then longer intervals) 

  • White granulated sugar ( applied daily until necrosis has cleared, then longer intervals) 

  • Activated carbon powder: fill the entire wound cavity with this powder. If the wound is drier, it can also be mixed with honey at a 50:50 ratio. 

  • Cotton gauze dressings. If the wound has much exudate, place the cotton gauze in dry. If the ulcer is drier, pre-moisten the gauze slightly with saline or, for example, 2% vinegar. You can use a 50:50 mixture of zinc paste and petrolatum jelly as a barrier layer over the entire wound surface to prevent the gauze from sticking to the wound bed. We recommend frequent dress g changes when using the gauze method. 

Secondary wound dressings if resources are limited:

  • cotton pads

  • ladies hygiene pads

Primary wound dressings, if all resources are available

  • Silver coated polyurethane dressings

  • Iodine containing polyurethane dressings

  • Sorbact

  • Polymem

Other treatment modalities (advanced):

  • Negative pressure wound therapy once the wound is clean and starting to show early granulation.

  • Platelet rich plasma (PRP) especially useful if there is exposed bone or tendon 

  • Partial thickness skin tranplant, ultra thin transfer of epidermal celle ( blister technique) or pinch/punch grafting

wa tropical ulcer 3.PNG

Figure 2  The images above show that tropical phagedenic ulcers in the acute phase can be turned in a positive direction reasonably quickly with an optimal treatment regime. The image to the left is upon admission. The wound was debrided, and frequent dressing changes were performed. The image to the right is after a week of treatment, and we can already see a lot of healthy granulation tissue forming. Within another week, the wound bed would be considered clean enough to do a partial thickness transplant if that was an option available to you. Alternatively, we would have to let it heal naturally. image rights: CDC/ K. Mae Lennon, Tulane Medical School; Clement Benjamin

Complications of tropical phagedenic ulcerations

  • The most common complication is the cosmetic results after the ulcer has healed. There will typically be a visible fibrotic scar, sometimes with abnormal pigmentation.

  • In tropical phagedenic, the infection and necrosis usually spread into the deep subcutaneous tissue but only rarely involves the bone. Osteomyelitis is a more rare complication here.

  • Recurrent ulcerations are known to occur- most commonly in children 

  • Squamous cell carcinoma may develop at the rate of 2 to 15% of the chronic ulcers that persist for more than three years. So if you have a patient who has had an ulcer for more than a couple of years, you should definitely do what you can to get a histopathological biopsy done. 

  • There have been reports of tetanus occurring in patients who have had tropical ulcerations. Check the patient's vaccination status if that is feasible, and carry out a tetanus vaccination if the vaccination status is unknown or if the last tetanus vaccine was more than ten years ago. 

  • Rarely are the ulcerations so severe that amputation is necessary. 

Preventing tropical phagedenic ulcers

  • Using shoewear

  • Using rubber boots when working in wet/muddy environments

  • Cleaning off the mud from legs after a day of work

  • Cleansing and applying antiseptics to minor cuts and bruises on the legs - for example, applying iodine tincture or gentian violet solution of 1%

  • Covering open cuts with fabric/dressings to prevent flies from landing on the wound

  • Draining pustules in an early phase to prevent ulcer formation

  • Education about what tropical ulcers are and that medical help should be sought when painful pustules appear. 

References:

Ghosh, D. (1946). Results of treatment of 200 cases of Naga-sore (tropical phagedenic ulcers). Indian Medical Journal, 40.

Kerleguer, A., Koeck, J. L., Girard-Pipau, F., & Nicand, E. (2003). Recrudescence of tropical phagedenic ulcers after the rainy season in Djibouti. Médecine Tropicale, 63(2).

Iqbal Akhtar, K. (2000). Tropical phagedena: A scar and a wound. Journal of Pakistan

Esterre, P., Pecarrère, J. L., Raharisolo, C., & Huerre, M. (1999). [Squamous cell carcinoma arising from chromomycosis. Report of two cases]. Annales de Pathologie, 19(6).

Association of Dermatologists, 10(OCT./DEC.).

Jané, L. P., Martínez, A. J., & Vila, A. M. (2007). Úlcera tropical. Medicina Cutanea Ibero-Latino-Americana, 35(5). https://doi.org/10.35434/rcmhnaaa.2021.141.908

Aribi, M., Poirriez, J., & Breuillard, F. (1999). Tropical phagedenic ulcer. European Journal of Dermatology, 9(4). https://doi.org/10.1097/00000658-195808000-00024

Blaine, G. (1958). Tropical phagedenic ulcer; evaluation of a new ambulatory method of treatment. Annals of Surgery, 148(2). https://doi.org/10.1097/00000658-195808000-00024

Yesudian, P., & Tmambia, A. S. (1979). METRONIDAZOLE IN THE TREATMENT OF TROPICAL PHAGEDENIC ULCERS. International Journal of Dermatology, 18(9). https://doi.org/10.1111/j.1365-4362.1979.tb05016.x

Robinson, D. C., Adriaans, B., Hay, R. J., & Yesudian, P. (1988). The Clinical and Epidemiologic Features of Tropical Ulcer (Tropical Phagedenic Ulcer). International Journal of Dermatology, 27(1). https://doi.org/10.1111/j.1365-4362.1988.tb02339.x