Assessment of lymphedema with lymphoscintigraphy: Can nodal quantification help?

Lymphoscintigraphy with combined qualitative and quantitative analysis is reported to be a more sensitive approach to diagnose lymphedema in comparison with the conventional clinical analysis. Our study seeks to evaluate the diagnostic performance of lower limb lymphoscintigraphy with amalgamation of qualitative and quantitative analysis by measuring the ilio-inguinal nodal uptake. This prospective observational study was comprised of 86 patients (172 limbs) diagnosed with lower limb lymphedema. After a thorough clinical grading of edema, radionuclide lymphoscintigraphy was performed as per a dedicated institutional protocol. Ilio-inguinal nodal quantification of tracer uptake was computed along with the visual study of the scans. Additionally, the corresponding mean nodal uptake percentage for each grade of lymphedema was assessed and a cut off nodal uptake percentage to differentiate between normal and abnormal limbs was defined. Although quantitative analysis with nodal uptake percentage provides objective criteria to diagnose lymphedema, it can only act as an adjunct to qualitative method without replacing it. Finally, standardization of procedure for quantitative lymphoscintigraphy is needed including the potential for combining both rate of clearance of tracer from injection site and nodal uptake for quantification.

Successful multi-modal treatment of grade IV lymphedema in lymphatic filariasis: A case study.

We present an integrated therapeutic approach performed on a 37 year old female with giant lymphedema (Grade IV) due to lymphatic filariasis of 27 years duration. Our therapeutic approaches consisted of a basic foot care program for two weeks, followed by a course of oral penicillin for a week including conservative treatment with complete decongestive therapy (CDT) together with respiratory physiotherapy and walking exercises. In addition, advanced surgical techniques with supra-fascial excision of alternate lumps in three stages over an interval of ten days followed by a nodo-venal shunt resulted in reversing the stage IV lymphedema condition. Over a ten year follow-up, the patient remains essentially unchanged confirming the success of the treatment without any recurrence or complications. Finally, by combining multimodal treatment, we were able to achieve a near normal limb in Stage III and Stage IV lymphedema of the lower limb in lymphatic filariasis.

An overview of lymphatic filariasis lymphedema.

Filariasis is caused by thread-like nematode worms and is classified according to their presence in the vertebrate host. The lymphatic group includes Wuchereria bancrofti, Brugia malayi, and Brugia timori. Lymphatic filariasis, a mosquito-borne disease, has been one of the most prevalent diseases in tropical and subtropical countries and is accompanied by a number of pathological conditions. It is estimated that currently (after 13 years of the MDA programme) there are an estimated 67.88 million LF cases that include 36.45 million microfilaria carriers, 19.43 million hydrocele cases, and 16.68 million lymphedema cases. Adult filarial worms reside in the lymphatics and lymph nodes and induce changes that result in dilatation of lymphatics and thickening of the lymphatic vessel walls. Progressive lymphatic damage and pathology results from the summation of the effect of tissue alterations induced by both living and nonliving adult parasites. In recent years, there has been rapid progress in filariasis research, which has provided new insights into the pathogenesis of filarial disease, diagnosis, chemotherapy, the host-parasite relationship, and the genomics of the parasite. We examined the clinical manifestations of the disease, diagnosis, treatment, immune responses, and management including review of pharmaceutical agents against filariasis. Details on infection, safety profile, and status in clinical practices are also reported.

GENITAL LYMPHEDEMA: A NEW TECHNIQUE OF CORRECTION SURGERY.

Genital lymphedema is a common problem seen by lymphology surgeons in India due to filarial infections. We have developed an innovative operative technique to correct this issue using native skin and have found the results in the first fifteen patients to be encouraging. Gross debulking procedures reduced the size and using native skin allowed a better cosmetic appearance. The patients also reported almost normal sensation and good sexualfunction. This technique deserves further testing with more patients and at additional centers.

Recombinant Wolbachia surface protein (WSP)-induced T cell responses in Wuchereria bancrofti infections.

Human lymphatic filariasis is a debilitating parasitic disease characterized by downregulation of the host's immune response in asymptomatic carriers along with profound hyperreactivity in chronic patients apart from putatively immune endemic normals. The endosymbiont Wolbachia, a bacterium of filarial nematodes has received much attention as possible chemotherapeutic target and its involvement in disease pathogenesis. The role of recombinant Wolbachia surface protein (rWSP), one of the most abundantly expressed proteins of the endosymbiont, in modulating cell-mediated immune responses in patients harboring Wuchereria bancrofti infections was evaluated in the current study. rWSP-induced lymphoproliferation with peripheral blood mononuclear cells suggested an impaired proliferative response in asymptomatic microfilaremic (MF) and symptomatic chronic pathology (CP) patients compared to endemic normals (EN). This was further supported by a significantly diminished expression of CD69 along with elevated levels of CD127 and CD62L in filarial patients (MF and CP) compared to EN. Further, rWSP induced the expression of regulatory T cell markers CTLA-4 and CD25 along with suppressor cytokines IL-10 and TGF-ß in MF and CP patients compared to EN. However, the rWSP-stimulated expression of IFN-γ was diminished significantly in filarial patients compared to endemic normals. Thus, these findings suggest that WSP may also contribute to the suppression of immune responses seen in filarial patients.

Immune responses to recombinant Brugia malayi pepsin inhibitor homolog (Bm-33) in patients with human lymphatic filariaisis.

Immune responses to recombinant Brugia malayi pepsin inhibitor homolog (rBm-33) were investigated in patients with human lymphatic filariasis (microfilaremics (MF) and chronic pathology (CP)) along with endemic normals (EN). Flow cytometric analysis (24 h) revealed CD4(+) T cell activation in patients (MF and CP) compared to normals (EN), with increased expression of CD69 and diminished levels of CD62L and CD127. This was associated with an elevated expression of CD154 but not CD28 and CTLA4 in CP patients. However, Bm-33-induced cytokine expression profile (IL-1ß, IL-12, IL-8, IFN-γ, IL-10 and TGF-ß) did not exhibit any significant difference between normals and patients at the same time point. Although CD4(+) T cell activation was observed initially in filarial patients (24 h), lymphoproliferation studies (96 h) suggested diminished proliferation compared to normals, indicating functional inactivation in the former upon prolonged antigen exposure. This indicates that rBm-33 induces an early T cell activation in MF and CP patients followed by a decreased lymphoproliferation that might contribute to immune suppression in these individuals.

Lymphoscintigraphy as a diagnostic tool in patients with lymphedema of filarial origin--an Indian study.

Lymphedema is a common clinical problem. Filariasis is the commonest cause of lymphedema in India and is a chronic debilitating disease. The purpose of this study is to highlight the role of lymphoscintigraphy in the evaluation of lymphedema. Our study population consisted of 418 patients diagnosed with filarial lymphedema of different clinical stages referred for lymphoscintigraphy of the limbs by the lymphologist at our institution. An analysis of the various studies was done to determine how lymphoscintigraphy can be useful in documentation of the diagnosis, evaluation, as a screening procedure to prevent progression, and to enhance management of filarial lymphedema.

The effectiveness of long-acting penicillin (penidur) in preventing recurrences of dermatolymphangioadenitis(DLA) and controlling skin, deep tissues, and lymph bacterial flora in patients with "filarial" lymphedema.

Dermatolymphangioadenitis (DLA) is a common and serious complication of so-called "filarial" and bacterial non-filarial lymphedema of the limb, affecting skin, lymphatics and lymph nodes. In our previous studies, we demonstrated that more than 60% of patients revealed presence of bacterial isolates in deep tissues, tissue fluid and lymph from the lymphedematous limbs. The question remained open whether elimination or suppression of bacteria dwelling in lymphedematous tissues by administration of low doses of penicillin for long time periods would prevent recurrence of DLA attacks. In this study, we retrospectively evaluated a self/community-selected group of patients with lymphedema of the lower limbs with respect to the efficacy of long-acting penicillin in preventing episodes of DLA. There were no microfilariae or anti-filarial antibodies detected in the investigated group. The questions we asked were: (a) how effective is the benzathine penicillin in preventing recurrences of DLA attacks and (b) how does its long-term administration influence the bacterial spectrum of leg skin, deep tissues, lymph and lymph nodes and sensitivity to antibiotics. Two randomly selected groups of patients, receiving and not receiving penicillin during the same period of time, were compared. Evidently lower recurrence rate of DLA was observed in the treated group (p < 0.002). There was increased prevalence of cocci and gram-positive bacilli with a concomitant decrease of gram-negative bacilli on the foot and calf skin surface. Simultaneously, decreased prevalence of gram-positive cocci and gram-negative bacilli isolates in limb deep tissues and lymph was seen. No resistance to penicillin and other tested antibiotics developed in isolates from the skin surface, deep tissues and lymph. We conclude that long-lasting penicillin is effective in preventing recurrent DLA attacks.

Oral submucous fibrosis-New dimensions in surgery.

The oral submucous fibrosis (OSMF) has been managed earlier by various medical and surgical modalities but none of these methods is found to give relief to these patients. Hence, a new method has been developed by us. Patients, who reported with pallor of the palate cheek, oropharyn and the tonsils, due to the fibrosis, leading on to mild, moderate to severe trismus, were given a good long-term rehef by this surgical method. This study involved 60 patients between 1979 and 2000 with a female-to-male ratio of 1∶3 with age ranging from 13 to 60 years suffering from the disease. The surgical method adopted in these cases used a single staged rotation tongue pedicle flap on either side from the dorsum of the tongue sutured to the raw area in the cheek without morbidity. In a 7-year follow up, we found the patients did not develop further fibrosis and the tongue flaps remained intact. The quality of life improved considerably and buccal mucosa is pink throughout the follow-up period. The modalities of treatment adopted are varied. Many tried the retro molar excision of the bands, which did not give long-term results. Others used excision of the whole fibrotic area with skin grafting, which also failed. Some have tried muscle pedicle flap from outside with postoperative morbidity and failure. Some surgeons have tried fat grafts in the cheek region (Yeh, Int J Oral Maxillo facial Surg 1996; 25; 130). The experience of the others who used versatile, vascular tongue flaps in the oral cavity after cancer clearance, prompted us to attempt this new technique in the present series with gratifying results. This is a break through in the surgical management of OSMF, where other treatment modalities failed.

Bacteriological studies of blood, tissue fluid, lymph and lymph nodes in patients with acute dermatolymphangioadenitis (DLA) in course of 'filarial' lymphedema.

Filarial lymphedema is complicated by frequent episodes of dermatolymphangioadenitis (DLA). Severe systemic symptoms during attacks of DLA resemble those of septicemia. The question we asked was whether bacterial isolates can be found in the peripheral blood of patients during the episodes of DLA. Out of 100 patients referred to us with 'filarial' lymphedema 14 displayed acute and five subacute symptoms of DLA. All were on admission blood microfilariae negative but had a positive test in the past. Blood bacterial isolates were found in nine cases, four acute (21%) and five subacute (26%). In 10 acute cases blood cultures were found negative. Six blood isolates belonged to Bacilli, four to Cocci and one was Sarcina. To identify the sites of origin of bacterial dissemination, swabs taken from the calf skin biopsy wounds and tissue fluid, lymph and lymph node specimens were cultured. Swabs from the calf skin biopsy wound contained isolates in nine (47%) cases. They were Bacilli in nine, Cocci in three, Acinetobacter and Erwinia in two cases. Tissue fluid was collected from 10 patients and contained Bacilli in four (40%) and Staphylococci in three (30%). Lymph was drained in four patients and contained isolates in all samples (100%). They were Staphylococcus epidermis, xylosus and aureus, Acinetobacter, Bacillus subtilis and Sarcina. Three lymph nodes were biopsied and contained Staphylococcus chromogenes, xylosus, Enterococcus and Bacillus cereus. In six cases the same phenotypically defined species of bacteria were found in blood and limb tissues or fluids. In the 'control' group of patients with lymphedema without acute or subacute changes all blood cultures were negative. Interestingly, swabs from biopsy wound of these patients contained isolates in 80%, tissue fluid in 68%, lymph in 70% and lymph nodes in 58% of cases. In healthy controls, tissue fluid did not contain bacteria, and lymph isolates were found only in 12% of cases. This study demonstrates that patients with acute episodes of DLA reveal bacteremia in a high percentage of cases. Diversity of blood and tissue bacterial isolates in these patients points to a breakdown of the skin immune barrier in lymphedema and subsequently indiscriminate bacterial colonization of deep tissues and spread to an blood circulation.

[Bacterial infections of skin and soft tissues in filariasis]. / Bakteryjne zakazenia skóry i tkanek miekkich w filariozie.

Adenolymphangitis is a common occurrence in filarial lymphedema. Damage to the lymphatics and lymph nodes by F. bancrofti is followed by obliteration of lymph vessels and lymph stasis. Obstruction of lymphatics prevents the bacteria penetrating skin to be evacuated with lymph stream to regional lymph nodes. Colonization of dermis, subcutis and lymphatics evokes clinical symptoms of adenolymphangitis. The question arises which strains of bacteria are responsible for the acute and chronic types of adenolymphangitis. The most probable strains responsible for this condition belong to the cocci and probably the bacillus strains.

Bacteriologic studies of skin, tissue fluid, lymph, and lymph nodes in patients with filarial lymphedema.

Filarial lymphedema is complicated by frequent episodes of dermatolymphangioadenitis (DLA). It is not certain whether DLA is of filarial or bacterial etiology. The frequency of episodic DLA does not depend on the presence or absence of microfilariae. Antibiotic therapy is effective in prevention and treatment of DLA. These observations point to the bacterial rather than filarial etiology of DLA. Skin and lymph node biopsies, tissue fluid, lymph, and blood from patients with chronic filarial lymphedema, and during acute episodes of DLA, were cultured for detection of bacteria. A high prevalence of bacterial isolates from the tissue fluid (64%), lymph (75%), and inguinal lymph nodes (66%) of limbs with filarial lymphedema was found. Bacillus cereus, Staphylococcus epidermidis, S. hominis, S. capitis, S. xylosus, and Micrococcus spp. were the most common isolates. Bacteria were also isolated from the blood of patients with recent episodes of DLA, with strains of the same phenotype and antibiotic sensitivity in all specimens from patients with DLA. Bacterial strains of the same phenotype and antibiotic sensitivity were documented on the toe web surface and in tissue fluid (25%), lymph (26%), or lymph nodes (41%). Increasing prevalence of bacterial isolates in tissue fluid, lymph, and lymph nodes was observed in advanced stages of lymphedema. Bacilli and cocci were sensitive to gentamicin, tetracyline, rifampicin, vancomycin, kanamycin and cotrimoxazole, and least sensitive to penicillin. Blood cultures of patients in the periods between DLA attacks were negative. In healthy controls without edema and episodes of DLA, tissue fluid did not contain bacteria. In lymph, only single colonies of Micrococcus and Acinetobacter were cultured in 12% of the cases. Impaired lymph drainage and lack of elimination of penetrating bacteria may be responsible for progression of lymphedema and recurrent attacks of DLA.

Skin changes in filarial and non-filarial lymphoedema of the lower extremities.

The pathogenesis of lymphoedema in patients infected with Wuchereria bancrofti or Brugia malayi remains unclear. Lymph stasis and local immunological reactions seem to play the main role. In order to discriminate between the obstructive and immunological effects of the parasite, a comparative histological study of skin specimens obtained from two groups of patients, one with filarial and the other with postsurgical lymphedema of lower extremities, was performed. In both groups patients suffered lymph stasis, in the first due to filariasis, in the other due to removal or irradiation of pelvic lymph nodes. The patients with filarial infection showed hyperproliferation of keratinocytes, focal acantholysis, accumulation of lymphocytes at the epidermo-dermal junction, profuse pericapillary and perivenular mononuclear infiltrations in the dermis marginated granulocytes in capillaries and, in some cases, subepidermal granulocytic infiltrates. There were many dilated initial lymphatics and lymphatic "lakes" between thick collagen fibre bundles. Monoclonal antibody analysis revealed that the most common cells in the infiltrates were macrophages (CD68+). All mononuclear and endothelial cells were HLA-DR+. In contrast, the skin specimens of non-filarial patients revealed only moderate proliferation of keratinocytes, increased numbers of CD1+ epidermal Langerhans cells, moderate pericapillary infiltrates of CD68+, CD4+ and CD8+ cells, and evidently less intensive marking of cells with anti-HLA-DR antibody. There were few initial lymphatics visible. These findings indicate that filarial lymphoedema is complicated by a severe inflammatory component, which is much less expressed in postsurgical lymph stasis.

Immune proteins in peripheral tissue fluid-lymph in patients with filarial lymphedema of the lower limbs.

Immune proteins and cytokine concentrations and activity were measured in skin tissue fluid-lymph and blood serum of patients with lower leg filarial lymphedema. High levels of lymph gamma-globulins, alpha-1-acid glycoprotein and IgG lymph/serum ratio were found. Lymph from filarial patients had an elevated lymph stimulatory effect on blood mononuclear cell culture with phytohemagglutinin. There was also a high concentration and activity of IL-1 beta but gamma-interferon was not detected. The deranged pattern of immune proteins and high activity of IL-1 suggest persistence of an ongoing local inflammatory process despite the absence of overt dermatitis. The high tissue-lymph IL-1 concentration and activity may signify a cytokine network promoting keratinocyte and fibroblast proliferation commonly seen on skin histology in patients with filariasis.

Incidence of burn wound sepsis in 600 burned patients treated in a developing country.

Infection is the most important problem in the treatment of burns in a developing country. A burn compromises a major body protective mechanism, namely the skin. Hence, the susceptibility to local infection increases at these sites. The incidence of burn wound sepsis is very high in south India as the socio-economic conditions and the standard of personal hygiene are poor and the hot moist climatic conditions encourage bacterial growth. These three factors are rarely present in the temperate zone countries of Europe and North America. This study was undertaken to identify more clearly the factors that are responsible for the higher incidence of burn wound infection and to formulate methods of treatment which are appropriate for our patient population living in a tropical country.