Trophic skin ulceration in leprosy: evaluation of the efficacy of topical phenytoin sodium zinc oxide paste.

BACKGROUND: The trophic or chronic plantar ulcer of leprosy is one of the principle causes of disability and deformity in the disease and has been given due importance in the evolution of its classification. In view of the diversity of its clinical implications, the World Health Organization was obliged to bring this entity under its remit in order to develop uniform guidelines to be applied around the globe. Despite relentless endeavor, its management continues to represent a dilemma. OBJECTIVES: The role of topical phenytoin sodium in wound healing led this group to evaluate its efficacy in the healing of trophic or chronic plantar ulcers. The success of the therapy was assessed according to the extent of regression in the size of the ulcer(s) following the formation of granulation tissue. METHODS: Forty patients released from leprosy control were recruited. A retrospective diagnosis was made in each case, and patients were grouped accordingly. Demographic data were recorded after the provision of informed consent. Bacterial cultures before and after treatment, and radiography were performed in each case. A phenytoin sodium fine powder zinc oxide paste dressing was applied every day for four weeks. Granulation was graded according to its appearance in order to evaluate the success of the topical therapy. RESULTS: Of the 40 patients, 26 (65.0%) borderline lepromatous leprosy patients had trophic ulcers, with the ball of the great toe being the most common site. Twelve (30.0%) patients had bone involvement. A total of 22 (55.0%) patients achieved complete resolution of the ulcer, and evidence of granulation formation was seen in 33 (82.5%) patients. The clearance of bacterial load after treatment was a significant finding. Zinc oxide paste per se was not effective, but its role as a vehicle was an asset. CONCLUSIONS: Phenytoin sodium zinc oxide paste was found to be an efficacious, cost-effective, and well-tolerated alternative therapy. Patient compliance was good. Bone involvement contributed to poor wound healing, but the clearance of bacterial load was significant.

Topical phenytoin for wound healing.

Oral phenytoin is used widely for the treatment of convulsive disorders and about half the patients treated develop gingival overgrowth as a side effect. The apparent stimulatory effect has prompted its assessment in wound healing. Studies have shown topical phenytoin to promote healing of decubitus ulcers, venous stasis ulcers, diabetic ulcers, traumatic wounds, burns, and leprosy trophic ulcers. The mechanism of action has been postulated to be multifactorial. The present literature indicates that topical phenytoin deserves further investigation as a wound-healing agent in controlled dose-finding clinical trials.

Cutaneous tissue repair: basic biology considerations. I

Wound repair of the integument is reviewed in the context of new developments in cell biology and biochemistry. Injury of the skin and concomitant blood vessel disruption lead to extravasation of blood constituents, followed by platelet aggregation and blood clotting. These events initiate inflammation and set the stage for repair processes. The macrophage plays a pivotal role in the transition between wound inflammation and repair (granulation tissue formation), since this cell both scavenges tissue debris and releases a plethora of biologically active substances that include growth factors. Although concrete evidence is lacking, growth factors are probably at least partially responsible for the angiogenesis and fibroplasia (granulation tissue) that gradually fill the wound void. If the epidermal barrier is disrupted during injury, reepithelialization begins within 24 hours and proceeds first over the margin of residual dermis and subsequently over granulation tissue. The signals for angiogenesis, fibroplasia, neomatrix formation, and reepithelialization in wound repair are not known, but a number of possibilities are discussed. Matrix remodeling is the last stage of wound repair and gradually increases the scar tensile strength to 70% to 80% of normal skin.

A new morphological concept and classification of granulomatous inflammation: the polar granulomas.

An historical analysis of granulomas and a new morphological concept and classification of granulomatous inflammation, the polar-granulomas, are presented. The historical analysis of the concept of granulomas reveals that the still proclaimed confusion concerning the process was due more to Virchow's comparison of granulomas to ordinary granulation tissue than to tumors and to objections of pathologists to Metchnikoff's theory of phagocytosis. And it is strange to verify that differences between granulomas and granulation tissue, although already established in the end of the 19th Century, were overlooked by the majority of pathologists. In this Century , the knowledge of granulomatous inflammation was greatly improved by Aschoff 's concept of reticulum endothelial system, Mitsuda test for types of leprosy, Jadassohn- Lewandowsky law, South American classification of leprosy into polar forms, and Forbus contribution to histogenesis and morphological classification of granulomas. The best model for the study of granulomatous inflammation is leprosy, because this disease is characterized by two different clinical polar forms, each one having particular types of phagocytosis (complete or incomplete) and of granulomas (tuberculoid or non tuberculoid). Based on the phenomenon of phagocytosis, polar forms of leprosy, Jadassohn- Lewandowsky law, metamorphosis of macrophages and nature of the etiologic agent, granulomas can be defined as a reactional hyperplasia of macrophages towards inanimate agents and towards animate agents of low virulence. Also based in the same data, a morphological classification of granulomas into polar types, tuberculoid and non tuberculoid, is proposed. The polar tuberculoid type follows the Jadassohn- Lewandowsky law, its etiologic agent is absent or scarce (complete phagocytosis) - and comprise two sub-types: tubercle-like and sarcoid-like. The polar non tuberculoid type does not follow the Jadassohn- Lewandowsky law, its etiologic agent is always present or copious (incomplete phagocytosis) and comprises two sub-types: giant cell and persistent macrophage. In the latter case, macrophages behave as a culture medium cell or as a storage cell. When both polar tuberculoid and non tuberculoid structures are found together in the same disease, granuloma can be called interpolar . If both types occur simultaneously in the same disease, granuloma would be bipolar. It seems that the proposed definition of granulomas combines morphology with functional activity of macrophages, easily observed in routine histopathological examination by optical microscopy. This morphological classification into polar granulomas (ABSTRACT TRUNCATED AT 250 WORDS)

Concepts of granulomatous inflammation.

Table 8 lists the patterns of the five discrete tissue reaction patterns of granulomatous inflammation and relates them to the predominant microscopic tissue reaction as well as to the dominant cell type present in the infiltrate. The possibility of a sixth group, granulation tissue, was also considered for this classification schema. The term "granulation tissue" was used by Virchow to define granulomatous inflammation. He probably used this term in a broader context than our present definition of granulation tissue (ie, fibrocapillary proliferation). Using the more narrow and perhaps more precise definition, we think that granulation tissue does not constitute a form of granulomatous inflammation.

Ocular leprosy in the Canal Zone.

The results of a two year survey of eye problems among the patients at the Palo Seco Hospital in the Canal Zone are presented. Only two patients, one classified as having lepromatous leprosy and the other as having the tuberculoid form of the disease, failed to exhibit ocular complications. The high prevalence of leprotic ocular disease (96%) is most probably due to the advanced age of the patients, the lengthy duration of their illness, and the high percentage of patients afflicted by the lepromatous form of the disease.