Non-healing Lesions Research Articles

Extramammary Paget's disease

E xtramammary Paget’s disease (EMPD) is an epithelial disorder usually observed in cutaneous apocrine gland-bearing regions. This condition may be associated with either subjacent or distant malignancies or may potentially be an invasive adenocarcinoma sui gene+. Clinically it is usually recognized as a nonhealing eczematous lesion. The diagnosis is confirmed histopathologically by the presence of Paget’s cells. Immunologic studies have revealed, however, that EMPD is an entity distinct from mammary Paget’s disease.

Lymphomatoid Papulosis

Lymphomatoid papulosis is an elusive and very rare skin disorder. It is clinically benign but histologically "atypical," and about 20% of affected patients go on to develop a lymphoreticular malignancy, usually Hodgkin's disease, or mycosis fungoides. A wide variety of treatments to prevent recurrence and improve local control have been suggested, but the results have been poor. We report on a patient with two nonhealing lymphomatoid papulosis lesions treated successfully with electron beam therapy and describe our technique. The need for close follow-up of all patients with this condition cannot be overemphasized.

A bacteriological and histological evaluation of 58 periapical lesions

Periapical tissue from 58 cases requiring periapical surgery was examined histologically and cultured for the presence of microbes. Twenty-nine had a possible oral cavity communication and 29 did not. Approximately one-half of each biopsy was submitted for culture while the other portion was examined histologically. Cultures were positive for the presence of bacteria in 51 of 58 cases while bacteria were seen histologically in only 8 of 58 cases. A total of 50 different species of bacteria were isolated from the 58 cultures of periapical tissue. Of 133 isolates, 87 were strict anaerobes, 37 were facultative anaerobes, and 9 were aerobes. Bacteroides species were found in 17 cultures, always with additional bacteria. Seventeen of 58 biopsies contained foreign particulate matter thought to be root canal sealer. Bacteria were found in periapical granulomas, radicular cysts, and a periapical abscess. According to our data, bacteria, foreign material, missed canals, vertical root fractures, and periodontal disease may all contribute to the chronic, non-healing periradicular lesion.

Basal cell, squamous cell, and sebaceous gland carcinomas of the periorbital region

It is important that clinicians suspect malignancy in patients who have persistent or nonhealing periorbital lesions. Basal cell carcinoma, squamous cell carcinoma, and sebaceous gland carcinoma of the eyelids are frequently misdiagnosed clinically and, in the case of squamous cell and sebaceous gland carcinomas, histologically as well. Prompt and adequate biopsy can facilitate early diagnosis and thus avoid unnecessary metastatic spread in the case of squamous cell carcinoma and sebaceous gland carcinoma, as well as the extensive local destruction that basal cell carcinoma may produce.

Perineal Hidradenitis Suppurativa

Two patients with advanced perineal hidradenitis suppurativa, complicated by fecal incontinence and squamous cell carcinoma, are presented. The first patient was a 58-year-old man who had a 30-year history of chronic recurring perianal abscesses and perineal sinuses. At the time of presentation, he had extensive perineal suppurative disease, and scarring and fixation of the anal sphincters with resultant fecal incontinence. He was treated with wide excision and skin graft closure. The second patient was a 27-year-old man with an 11-year history of recurrent gluteal abscesses and perineal sinuses. At the time of presentation, his inflammatory disease was only mildly active, but he had a nonhealing gluteal lesion. The nonhealing lesion was diagnosed as a squamous cell carcinoma and was managed with wide excision and primary closure. The inflammatory disease was excised and grafted. Complications of advanced hidradenitis suppurativa can be debilitating and life threatening. We review the etiology, pathophysiology, complications, and treatment options of hidradenitis suppurativa, including a literature review of the association with malignancy. We propose that the incidence of disabilities and complications may be reduced by early diagnosis and treatment, by emphasis on prevention of recurrence, and by more aggressive surgical intervention for recurrent and extensive disease.

Morphology of Human Epidermal Healing

Tissues obtained at surgical treatment for pressure sores, venous ulcers and bum injuries have been investigated using immunohistochemical techniques. Non-healing lesions show very disorganised epidermal/granulation tissue boundaries and have extra-cellular plasminogen. Healing wounds show superficial advancement of epidermal cells and cellular plasminogen staining. All leading epidermal edges lay down their basement membrane components, collagen IV and laminin after the cell sheet has advanced.

Closure of refractory perineal Crohn's lesion

A case is reported in which a comprehensive program of hyperbaric oxygen (HBO), surgical debridement and reconstruction, and continuing medical management resulted in complete and sustained closure of an extensive perineal Crohn's lesion refractory to conventional medical and surgical management. It is emphasized that in this case healing occurred in the setting of previous removal of all diseased intestinal tissue and only with the combined use of all three treatment modalities. HBO may be a useful adjunct in the therapy of large nonhealing perineal lesions post-proctocolectomy in patients who are unresponsive to metronidazole or to immunosuppressant therapy or who experience limiting side effects from continued medical therapy.

Cutaneous Habronemiasis in a Dog

Cutaneous habronemiasis (summer sores), a common condition in horses, is characterized by ulcerative, non-healing skin lesions and the formation of exuberant granulation tis~ue.~.6.~.9 It is caused by aberrant intradermal migration by third-stage larvae (juveniles) of equine spiruroid stomach worms, Habronema musca, Habronema microstoma, and Draschia megastoma. 1,4,6~10 The normal life cycle of these nematodes involves development into the infective thirdstage larvae in a muscid intermediate host.4 Infective larvae are deposited by the adult fly on the mouth and lips of horses and are then swallowed and mature to adults in the stomach. Cutaneous infections occur when infective larvae are deposited by flies feeding in moist areas or open wounds instead of the mouth and lips. Experimentally, it has been demonstrated that infective larvae can penetrate normal, intact skin.4 Areas frequently involved include the lower limbs, medial canthus of the eye, the urethral process, and prepuce.’ There are no previous reports of this condition in other species. This report describes a case of cutaneous habronemiasis in a dog. In early July, a 9-year-old, spayed female, mixed-breed dog was examined because of a large, ulcerated lesion on the face. This lesion started as a small swelling lateral to the right naris. During the following 2 weeks, the lesion ulcerated and spread to involve most of the right side of the nose and face rostra1 to the medial canthus of the right eye. A biopsy from the edge of the lesion was fixed in 10% neutral buffered formalin and submitted for histopathologic evaluation. Histologically, the epidermis was ulcerated and overlaid with a thin layer of necrotic cellular debris admixed with neutrophils. The dermis and subcutis were markedly edematous and contained extensive infiltrates of inflammatory cells, predominantly eosinophils, with fewer plasma cells, macrophages, and lymphocytes. Variably-sized tracts of necrotic cellular debris admixed with fragmented collagen and large numbers of degenerate eosinophils were also present in

Lower Extremity Amputation: Open Versus Closed

Wound breakdown was assessed in 117 amputations for nonhealing lesions and peripheral vascular closure (chi 2 10.34). Nonhealing occurred in 10/63 amputations with primary skin closure when compared with those not closed (p less than .01). All 54 amputation sites treated by the open technique healed without revision. Of 22 toe amputations, the open technique performed in 14 patients required a mean of nine postoperative days; the closed-toe amputation technique performed in 8 patients needed a mean of 5.8 days; the closed-toe amputation requiring revision needed a mean of 36.3 days. Healing rates were significantly different when the wound was left open versus primarily closed (chi 2 8.56 p less than .01). Nineteen transmetatarsal amputations (TMA) were completed; 10 open TMAs required a mean of twenty-four days; 9 closed TMAs required a mean of fifteen days; and revision a mean of eighteen days. Of 51 below-the-knee amputations (BKA), 20 open BKAs required a mean of thirteen days; 3 closed BKAs required a mean of 18.5 days; and 1 revision required two hundred fifty-eight days postoperatively. Twenty-five above-the-knee amputations (AKA) were performed; the 10 open AKAs required a mean of sixteen days; the 15 closed AKAs required a mean of eleven days. There was no significant difference in healing rates of TMA, BKA, or AKA. Healing rates of toe amputations and amputation overall are, however, significantly different. Closed lower extremity amputation wounds require fewer hospital days than open, except if problems in wound healing require revision.

Mucocutaneous Dissemination of Acyclovir-Resistant Herpes Simplex Virus in a Patient with AIDS

Infections caused by herpes simplex virus (HSV) are a significant source of morbidity in immunocompromised patients. Acyclovir is often used prophylactically and therapeutically in patients with human immunodeficiency virus infection. The emergence of acyclovir-resistant strains of HSV capable of causing disease has been recognized. We report a case in which a thymidine kinase-deficient mutant of HSV caused extensive disease in a patient with AIDS. This case emphasizes that virus recovered from nonhealing lesions should be submitted for further study, which may advance our understanding of the interaction between host defense and drug-resistant strains.

Sex differences and cross-immunity in DBA/2 mice infected with L. mexicana and L. major.

Female DBA/2 mice were found to be highly resistant to Leishmania mexicana and rarely developed lesions even when inoculated subcutaneously with high numbers (5 x 10(6] of amastigotes. Male DBA/2 mice, on the other hand, were much more susceptible to this parasite and often developed non-healing lesions even when inoculated subcutaneously with comparatively few (5 X 10(4] amastigotes. Conversely, although both male and female DBA/2 mice developed ulcerating lesions when inoculated subcutaneously with L. major amastigotes, lesions invariably healed in males but did not heal in females. Male DBA/2 mice recovered from L. major infection subsequently were found to be resistant to subcutaneous challenge with L. mexicana. Conversely female DBA/2 mice that had failed to develop lesions when infected with L. mexicana developed lesions which healed following subcutaneous challenge with L. major. Thus there is bilateral cross-immunity between L. mexicana and L. major in DBA/2 mice which overrides differences in sex-determined susceptibility to both organisms.

Ulcerated Below-the-Knee Stump

Ulcerative lesions appearing on a below-the-knee (BK) stump often delay permanent prosthesis fitting and rehabilitation or prevent the user of a perma nent prosthesis from resuming the ambulatory state. Seventeen patients (11 men, 6 women), with an average age of 61.4 (range 52 to 71) years, had under gone BK amputation for vascular disease (rest pain or gangrene, or both, with ankle:brachial index ratios < 0.15); 5 patients (3 men, 2 women) had diabetes controlled with insulin. All patients had a history of smoking with associated cardiovascular disease determined by physical examination or electrocardio gram, or both. Fourteen patients did not have initial healing after their BK amputation; the other 3 had a BK amputation in the distant past (twelve, eight een, and twenty months previously) and a nonhealing ulcer. All patients were referred for revision to an above-the-knee (AK) amputation; none came to AK amputation. All patients were treated with intravenous cephalosporins, de bridement, whirlpool, fine mesh gauze dressings, and a softstem air splint. The air splint prosthesis allowed proprioception, balance, gait, and total contact compression at 25 mm Hg when ambulatory. All wounds healed in fourteen to twenty-four days, allowing return to the permanent prosthesis in 3 patients and early measurement and fitting (no delay) of the remaining 14 patients for a permanent prosthesis. The softstem air splint temporary prosthesis represents an adjunctive measure in management of a nonhealing lesion on the stump of a BK amputee. It can facilitate rehabilitation via maintenance of gait, pro prioception, balance, and shape.

Wound healing and dermatologic dressings

The problem of optimal wound healing is not a new one; however, much attention is now being focused on this, as witnessed by several recent reviews. 1–5 In addition, there has also been a similar focus on changes in the skin that modify optimal wound healing. It has been traditional to categorize healing by primary and secondary intent, and this is a part of the basic vocabulary and elementary education of any surgeon. More recently, this has become an increasingly familiar part of the practice of dermatology with its growing surgical emphasis. Indeed, the ultimate calling card for a successful surgeon is the patient's postoperative scar (or lack of same). The increase in surgical procedures performed by dermatologists has been part of the renewed impetus for research in wound healing in this specialty. Further, the immense public cost of slowly healing or nonhealing lesions (diabetic ulcers, decubitus ulcers, etc.) has further focused federal National Institutes of Health funding on the problem, increasing the support for the investigations. Because surgery is now an important part of daily practice of many dermatologists, an awareness of advances in this area has become essential. Advances in dermatologic dressings are having increasing impact in practice. They accelerate the healing process and in many instances provide a better cosmetic result. These new dressings are appropriate for wounds healing by both primary intent and secondary intent. Let us briefly review both processes and the indications for dressings.

The correlation between delayed hypersensitivity, lymphocyte activation and protective immunity in experimental murine leishmaniasis.

The growth of Leishmania major and Leishmania mexicana lesions and the concomitant development of delayed-type hypersensitivity (DTH) to homologous or heterologous soluble antigen was studied in BALB/c and CBA/Ca mice. Although CBA/Ca mice are highly susceptible to L. mexicana, developing non-healing lesions, they are resistant to L. major; while BALB/c mice develop non-healing lesions when infected with either species. The development of resistance was associated with the acquisition of DTH which peaked at 48 h (L. major infected CBA/Ca mice). Non healing lesions were associated with either negative DTH (L. major infected BALB/c mice) or DTH that peaked at 24 h but had significantly subsided by 48 h (L. mexicana infected CBA/Ca and BALB/c mice). The latter response was associated with basophilic infiltration of the skin test site. Pre-irradiating (600 rad) CBA/Ca and BALB/c mice induced resistance against L. mexicana and L. major respectively in conjunction with the appearance of 48 h DTH to the homologous antigen. There was clear dissociation in the skin reactivity produced by the heterologous antigen. Thus L. major-derived antigen failed to produce DTH in L. mexicana infected mice of either strain. L. mexicana-derived antigen on the other hand produced a quicker response and of greater magnitude than the homologous antigen in L. major infected CBA/Ca mice. This correlated well with the strong cross-immunity induced by L. major in these mice to L. mexicana infection.

Distal revascularization and microvascular free tissue transfer: An alternative to amputation in ischemic lesions of the lower extremity

Most lower extremity amputations result from complications of diabetes and arteriosclerotic occlusive diseases below the inguinal ligament. Improved limb salvage has been achieved by an aggressive approach to distal revascularization in the severely ischemic lower extremity. There remains, however, a high incidence of amputation resulting from progression of the ulceration or gangrene into deeper and less well-vascularized tissues, such as tendon and bone. Even in the nonischemic extremity, such wounds rarely heal without flap coverage. Microvascular free tissue transfers promote healing by providing coverage with healthy, nondiseased, well-vascularized tissue for these difficult defects. Successful free flap transfer requires a high-pressure recipient inflow vessel. In contrast to individuals with nonarteriosclerotic lesions, many individuals with nonhealing ischemic lesions have no acceptable artery demonstrated on high-resolution angiography to serve as a recipient vessel. Limb salvage has been achieved in four candidates for amputation utilizing distal revascularization followed by free tissue transfer coverage of the ischemic lower leg defects.

Response of BALB/c mice to leishmanial infection.

Inbred mouse strains have played an important role in genetic analysis of the various immune mechanisms which regulate leishmanial infections in the host. In these studies early resistance and susceptibility (Bradley 1977), as well as curing versus noncuring (Blackwell, Freeman & Bradley 1980) and healing versus nonhealing (Howard, Hale & Chan-Liew 1980) responses, have been shown to be under the control of separate genes which, with only one exception (Blackwell, Hale, Roberts, Ulczak, Liew & Howard 1985), act against Leishmania species causing visceral but not cutaneous disease or against one cutaneous species but not another (reviewed by Blackwell 1985; Blackwell & Alexander 1985). Hence, individual mouse strains may be equisitely sensitive to one species of Leishmania but quite resistant to another, even though the species may share the same tissue tropism. CBA/Ca mice, for example, are resistant to visceral infection following intravenous (iv) inoculation of L. donovani, develop self-healing lesions following subcutaneous (sc) inoculation of L. major, but maintain large nonhealing lesions even after sc inoculation of relatively low doses of L. mexicana mexicana. C57BL/10ScSn (B10) mice show early susceptibility but later self-cure with L. donovani, develop self-healing lesions with L. major, and nonhealing lesions with L. m. mexicana.

Immunoprophylaxis in BALB/c mice: a model for development of protection against primary and secondary infection with Leishmania major.

BALB/c mice develop both nonhealing cutaneous lesions and fatal systemic disease following subcutaneous (sc) inoculation of the protozoan parasite, Leishmania major. Several interesting features characterize this fulminant infection, and set BALB/c mice apart from other susceptible strains: (1) fatal disease in the BALB/c is virtually independent of infective parasite dose (Howard, Hale & Chan-Liew 1980), (2) a macrophage defect(s) appears to underlie the innate susceptibility of BALB/c mice to this strain of Leishmania (Behin, Mauel & Sordat 1979; Handman, Ceredig & Mitchell 1979; Nacy, Fortier, Pappas & Henry 1983; Mitchell, Anders, Brown, Handman, Roberts-Thomson, Chapman, Forsyth, Kahl & Cruise 1982) and (3) immunosuppression attributed to either lymphocytes (Howard, Hale & Liew 1980) or macrophages (Scott & Farrell 1981) develops in the later stages of infection, possibly the net result of vigorous parasite proliferation in defective macrophages.

Susceptibility of inbred mice to Leishmania tropica infection: genetic control of the development of cutaneous lesions in P/J mice.

Leishmania tropica infections of P/J mice are characterized by the development of progressive nonhealing cutaneous lesions, followed by visceral metastases to liver and spleen. To analyze the genetic control of this disease, we produced F1, backcross (BX), and F2 progeny by breeding susceptible P/J mice with L. tropica-resistant C3H/HeN mice. Infections in these hybrid animals suggested that genetic control of the cutaneous lesion was by a single, autosomal, dominant gene. Resistance was the dominant trait. Analysis of liver and spleen impression smears in these animals, however, indicated that development of the cutaneous lesion segregates independently of the second component of L. tropica infections, systemic disease.

Resistance to macrophage-mediated killing as a factor influencing the pathogenesis of chronic cutaneous leishmaniasis.

Cutaneous leishmaniasis can be either a spontaneously healing or chronic disease, depending upon the strain of parasite and the immunological status of the host. We have investigated parasite factors responsible for the variable pathogenesis observed in leishmanial infections by testing the sensitivity of several leishmanial strains to intracellular killing in lymphokine (LK) activated mouse macrophages. Significant microbicidal activity against Leishmania tropica, a strain which heals in C57BL/6 (B6) mice, was found. In contrast, a strain (Maria) which has previously been shown to induce chronic nonhealing cutaneous lesions in B6 mice was resistant to killing in activated macrophages. This resistance to killing was observed in macrophages activated by LK obtained from either Bacille Calmette-Guérin-, L. tropica, or the Maria strain infected mice. The inability of LK activated macrophages to kill the Maria strain was shown not to be due to parasite induced inhibition of killing mechanisms, since Maria strain infected, LK treated macrophages exhibited tumoricidial activity similar to uninfected macrophages. Furthermore, LK activated macrophages simultaneously infected with the Maria strain and another intracellular pathogen, Toxoplasma gondii, killed Toxoplasma, but not the Maria strain. Temperature was also found to significantly influence the multiplication and killing of Leishmania parasites. As would be expected from their cutaneous nature, L. tropica and Maria strain parasites multiplied better at 35 degrees C than at 37 degrees C. Also consistent with the failure of cutaneous strains to visceralize in immunocompetent mice was the observation that the killing of leishmanial parasites was enhanced at the higher temperature. Thus, the temperature dependent growth capacity and sensitivity to killing of a given leishmanial strain in macrophages may be important factors influencing the pathogenesis of cutaneous leishmaniasis.

Immunodepression in BALB/c mice infected with Leishmania tropica.

Leishmania tropica is an obligate intracellular parasite of macrophages which causes cutaneous leishmaniasis in man. Infections in BALB/c mice with this parasite are characterized by the development of large primary ulcers and multiple non-healing metastatic cutaneous lesions (1,2,3). To date, the immunological mechanisms responsible for the inability of BALB/c mice to resolve leishmanial infections are unknown; however, specific suppressor T cells responsible for regulating skin test responses to leishmanial antigens have been reported (3,4). In addition, BALB/c mice infected with L. tropica develop a non-specific immunodepression, as described in this report. This immunodepression is mediated by an adherent suppressor cell which suppresses mitogen and leishmanial antigen responses in a lymphocyte transformation assay.