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To present the clinicopathological features and the practice of diagnosing infectious cutaneous granulomas in Egypt.
Methods
This study included all cases diagnosed with infectious cutaneous granuloma during the period 2004–2010 at Al-Hussein University Hospital, Cairo. Clinical and histological features were recorded, along with the positivity rate (PR) for each diagnostic method.
Results
This study included 233 cases (150 males and 83 females) with a mean age of 47 years. Three groups of infection were recorded: bacterial infections (73.8% Mycobacterium and 3.9% non-Mycobacterium), parasitic infestations (16.7%), and deep fungal infections (5.6%). Tuberculosis cases formed the largest granuloma group (40.8%), followed by leprosy (31.7%) and leishmaniasis (15.9%). A total of 36 cases were diagnosed by direct smear (PR 15.5%), 61 cases by skin biopsy (PR 31.0%), 84 cases by intradermal test (PR 63.6%), 26 cases by serological tests (PR 60.5%), 18 cases by tissue culture (PR 69.2%), and eight cases by PCR (PR 100%).
Conclusions
Mycobacterial infections constitute the most common infectious cutaneous granulomas among Egyptians. Routine methods such as direct smear, skin biopsy, and intradermal tests remain the most commonly applied and economical methods for diagnosis in developing countries, although specific methods such as tissue culture and PCR have higher positivity rates in the diagnosis.
Cutaneous granulomas are usually classified as infectious or non-infectious according to the presence or not of pathogenic organisms. The hallmark of a granulomatous reaction is the collection of activated histiocytes in an epithelioid manner. The presence of other inflammatory cells such as lymphocytes, plasma cells, and neutrophils, in addition to multinucleate giant cells, is usually determined according to the pattern and severity of the inflammatory response.
In some instances, the distinction between infectious and non-infectious granulomas may be difficult and these may be hard to distinguish. Although infectious granulomas usually reveal necrosis and abscess formation, non-infectious ones also occasionally reveal necrosis. The balance between the pathogenic organisms and defense mechanisms of the host usually determines the histological pattern of the granulomas – either suppurative or non-suppurative.
There are two common patterns of granulomatous dermatitis, nodular and diffuse. The reaction pattern is considered nodular when discrete perivascular inflammation extends beyond a single perivascular region and is relatively large and dense. In the diffuse pattern, the cellular infiltrate is dense enough that discrete cellular aggregates cannot be recognized. The pattern of the granuloma is usually determined according to many features, including the distribution of the infiltrate (superficial or deep), the inflammatory cell composition, and the presence or absence of necrosis, foreign bodies, infectious organisms, epidermal changes, etc.
In this study, we present the clinicopathological features and the practice of diagnosing infectious cutaneous granulomas in Egypt.
2. Patients and methods
This study included all cases diagnosed with infectious granulomas during a 6-year period (2004–2010) at Al-Hussein University Hospital, Cairo, Egypt. Clinical data were recorded for each patient, including age, sex, and duration of the disease, in addition to the morphology, location, and distribution of the lesions. Family history, history of previous skin or systemic diseases, and drug therapy were also recorded.
The diagnostic tools used included direct smear, skin biopsy, intradermal skin tests, serological tests, tissue culture, and polymerase chain reaction (PCR). The diagnostic tests were done sequentially starting with simple, low-cost methods (smear, then biopsy, and subsequently intradermal skin tests), followed by specific high-cost methods (serological tests, then tissue culture, and subsequently PCR). The diagnostic method was recorded for each case as the first conclusive method that detected the infectious agent or was highly suggestive of its presence, even if it was confirmed by other diagnostic methods. The positivity rate (the number of positive cases in relation to the total number of tested cases) was recorded for each method.
The special stains that were used in both direct smear and skin biopsy included Gram, Giemsa, periodic acid–Schiff (PAS), Gomori's methenamine silver (GMS), Ziehl–Neelsen (ZN), and modified Ziehl–Neelsen (Wade–Fite method), in addition to other stains that were used to exclude other non-infectious granulomas, such as reticulum, Verhoeff–van Gieson (VVG), and alcian blue. Intradermal skin tests included the Mantoux test for tuberculosis (TB), lepromin skin test for leprosy, and leishmanin skin test for leishmaniasis. Serological tests included QuantiFERON for TB, phenolic glycolipid-1 (anti-PGL-1) for leprosy, Schistosoma mansoni soluble egg antigen (anti-SmSEA) for schistosomiasis, and the venereal disease research laboratory (VDRL) and Treponema pallidum hemagglutination (TPHA) tests for syphilis.
Laboratory and radiological tests were done routinely for all patients and included the complete blood count (CBC), liver and renal function tests, erythrocyte sedimentation rate (ESR), chest X-ray, and abdominal ultrasound. Medical photography was performed for some cases after obtaining written consent. Follow-up was done for all patients with monitoring of their therapeutic response.
3. Results
A total of 233 cases confirmed as having an infectious granuloma were enrolled in this study. The annual detection rate was 38.8 cases/year. Male patients (n = 150) constituted 64.4% of the study population, while female patients (n = 83) constituted 35.6%; the male to female ratio was 1.8:1. Patient age ranged from 22 to 81 years, with a mean age of 47 years.
Three groups of infection were recorded: bacterial infections (73.8% Mycobacterium and 3.9% non-Mycobacterium), parasitic infestations (16.7%), and deep fungal infections (5.6%). Out of 233 cases, 36 were diagnosed by direct smear (PR 15.5%), 61 cases by skin biopsy (PR 31.0%), 84 cases by intradermal skin test (PR 63.6%), 26 cases by serological test (PR 60.5%), 18 cases with tissue culture (PR 69.2%), and eight cases by PCR (PR 100%). The data are summarized in Table 1.
Table 1The spectrum of infectious cutaneous granulomas in 233 Egyptian patients with results of the common diagnostic methods
Tuberculosis (TB) cases formed the largest infectious granuloma group in this study (95 cases), with four clinical variants: lupus vulgaris (LV) n = 59 cases (62.1%), scrofuloderma n = 16 cases (16.8%), tuberculosis verrucosa cutis (TBVC) n = 14 cases (14.7%), and tuberculids n = 6 cases (6.3%). The positivity of the diagnostic methods for each variant type is shown in Figure 1a .
Figure 1The positivity of the different diagnostic methods in (a) various subtypes of cutaneous tuberculosis (LV, lupus vulgaris; SF, scrofuloderma; TBVC, tuberculosis verrucosa cutis; Tu, tuberculids) and (b) leprosy (TT, tuberculoid type; BT, borderline tuberculoid; BL, borderline lepromatous; LL, lepromatous leprosy).
Lupus vulgaris (59 cases) showed a clinical presentation of reddish-brown, soft infiltrated nodule or plaque in 42 cases (71.2%), with a solitary lesion in 34 cases (57.6%) and multiple lesions in eight cases (13.6%). Atypical lesions were reported in 17 cases (28.8%): nine annular (15.2%), two sporotrichoid (3.4%), two vegetating (3.4%), and four ulcerative (6.8%). The lesions were located on the face (Figure 2a) in 36 cases (61.0%), on the extremities in 20 cases (33.9%), and at both sites in three cases (5.1%).
Figure 2A case of lupus vulgaris showing (a) large infiltrated reddish plaques on the face and neck, (b) a non-caseating granuloma in the superficial dermis (H&E section, × 2), and (c) epithelioid histiocytes admixed with lymphocytes and multinucleate Langhans giant cells (H&E section, ×40).
Histologically, two patterns were recognized in LV: in 45 cases (76.3%) a nodular non-caseating granuloma was characteristic, with formation of one or more tubercles in the upper dermis (Figure 2b); each tubercle showed a central collection of epithelioid histiocytes surrounded by a rim of lymphocytes admixed with multinucleate giant cells, usually of Langhans or foreign body type (Figure 2c). In the remaining 14 cases (23.7%), the granulomatous reaction was characterized by nodular caseating granuloma with central caseation necrosis. Epidermal changes were seen in 51 lesions (86.4%), including acanthosis, hyperkeratosis, parakeratosis, and scale-crust formation.
In LV cases, TB bacilli were not detected by direct smear or skin biopsy, but they were isolated in seven cases (11.9%): six by tissue culture and one by PCR. For the remaining 52 cases (88.1%), the diagnosis was suggested by the tuberculin skin test (TST) in 37 cases and by QuantiFERON in 15 cases. All cases of LV were followed-up after treatment with anti-TB therapy (isoniazid, rifampin, and pyrazinamide for 2 months, followed by isoniazid and rifampin for 4 months). In 44 cases (74.6%) significant improvement was seen at the end of the standard treatment period (6 months), while in 15 cases (25.4%) the treatment was continued for up to 1 year before a significant improvement was achieved.
Scrofuloderma cases (n = 16) presented with ulcerated reddish nodules on the neck (seven cases), axilla (five cases), mandibular area (two cases), and inguinal region (two cases). Histologically, scrofuloderma was characterized by nodular tuberculoid granuloma with prominent caseation necrosis and a dense inflammatory infiltrate. TB bacilli were detected in 11 cases (68.7%), two by direct smear, seven by skin biopsy, one by culture, and one by PCR, while in the remaining five cases (31.3%), the diagnosis was suggested by TST in three and QuantiFERON in two.
TBVC cases (n = 14) presented clinically with a solitary verrucous plaque with superficial fissuring, ulceration, oozing, and crust formation; 10 cases were located on the foot and four cases on the hands. Histologically, TBVC was characterized by prominent epidermal changes, including acanthosis, hyperkeratosis, scale-crust formation, and intrafollicular neutrophilic abscesses, while in the dermis the lesion showed nodular tuberculoid granuloma with caseation necrosis and a dense inflammatory infiltrate, usually less dense than observed in scrofuloderma. TB bacilli were isolated in eight cases (57.1%), three by skin biopsy and five by culture, while in the remaining six cases (42.9%) the diagnosis was suggested by TST (five cases) and QuantiFERON (one case).
Tuberculid cases (n = 6) included four presenting clinically as erythema induratum and two as lichen scrofulosorum. Histologically, erythema induratum showed lobular panniculitis and variable degrees of fat necrosis associated with a granulomatous reaction and vasculitis, while lichen scrofulosorum showed a superficial tuberculoid non-caseating peri-follicular and peri-appendageal granulomatous reaction. All cases were known cases of pulmonary TB who showed reactivation of their chest focus 4–7 months before the development of their skin lesions. All patients were strongly positive by TST, which together with chest X-ray, elevated ESR, and neutrophilia, suggested the diagnosis.
Leprosy was recorded in 74 cases, with four clinicopathological variants: the lepromatous group included 31 cases (41.9%) of borderline lepromatous (BL) and 20 cases (27.0%) of lepromatous leprosy (LL), and the tuberculoid group included 12 cases (16.2%) of tuberculoid type (TT) and 11 cases (14.9%) of borderline tuberculoid (BT).
BL leprosy (31 cases) was the most common subtype among the leprosy cases. Clinically, it presented with multiple bilateral reddish infiltrated papulo-nodular skin lesions, more often located on the extremities (Figure 3a) . The pathological features were characterized by an upper dermal diffuse and lower dermal nodular granulomatous infiltrate formed of histiocytes (some showed a foamy appearance), with a few lymphocytes, plasma cells, and multinucleate giant cells (Figure 3b). In lepromatous leprosy, the clinical presentation was similar to BL, but with a more widespread and symmetrical distribution, while pathologically it showed a pandermal diffuse infiltrate separated from the epidermis by a clear zone and formed of foamy histiocytes with variable numbers of plasma cells. Lepra bacilli were detected in all cases in the lepromatous group (51 cases): 24 cases (47.0%) by skin biopsy (Figure 3c), eight cases (15.7%) by nasal smear (Figure 3d), and 19 cases (37.3%) by slit-skin smear. The morphological index (MI) showed a median range in the lepromatous group ranging from 40 to 60 viable bacilli/100 bacilli, while the bacterial index (BI) showed a higher range in LL (5–6) compared with BL (3–5).
Figure 3A case of borderline lepromatous leprosy showing (a) infiltrated nodules on the thigh, (b) a superficial diffuse and deep nodular granulomatous infiltrate (H&E section, ×2), (c) intact Mycobacterium leprae with globi (Fite stain, ×100), and (d) positive nasal smear.
The diagnostic challenge was more obvious in the tuberculoid group (23 cases). Clinically, well-defined hypopigmented or erythematous patch(es) with sensory impairment and low hair density was the most common presentation. Solitary lesions were found in five cases (21.7%), while multiple lesions were recognized in 18 cases (78.3%). In 15 cases (65.2%), the lesions were located on the extremities, while in eight cases (34.8%), the lesions were located on the face and neck; there was thickening of the peripheral nerves in 12 cases (52.2%). The main histological features of this group were the presence of deep dermal peri-adnexal, perivascular, and peri-neural granulomatous infiltrates formed of epithelioid histiocytes surrounded by lymphocytes. Plasma cells were seen in 10 cases (43.5%), while a lymphocytic infiltrate around the deep dermal nerves was seen in 13 cases (56.5%). Lepra bacilli were not detected by direct smear in any case, while two cases showed lepra bacilli in skin biopsy. The diagnosis was suggested by a positive lepromin skin test in 13 cases and a positive anti-PGL-1 in eight cases (Figure 1b). All cases in the tuberculoid group were monitored for up to 1 year after receiving multi-drug therapy (MDT); 16 cases (69.6%) showed complete improvement after they had completed 6 months of treatment, while seven cases (30.4%) showed complete improvement after 10 months.
Cutaneous leishmaniasis (CL) (n = 37) showed a clinical presentation of a solitary nodular or plaque lesion with an ulcerative surface (Figure 4a) in 31 cases (83.8%), while three cases (8.1%) showed the sporotrichoid form, two cases (5.4%) showed a verrucal plaque, and one case (2.7%) showed disseminated nodules. Three granulomatous patterns were recognized, including a nodular non-suppurative pattern (Figure 4b) in 23 cases (62.2%), a diffuse non-suppurative pattern in nine cases (24.3%), and a diffuse suppurative pattern in five cases (13.5%). Epidermal changes including acanthosis, hyperkeratosis, and scale-crust were constant features in 32 cases (86.5%), while plasma cells were present in all cases (100%). Leishmania amastigotes (Leishman–Donovan bodies) were detected in 17 cases (45.9%): three cases by direct smear, seven cases by skin biopsy (Figure 4c), two cases by tissue culture, and five cases by PCR. The diagnosis was suggested by leishmanin skin test in the remaining 20 cases (54.1%). A total of 25 cases (67.6%) were successfully treated with cryotherapy as a single treatment method, while 12 cases (32.4%) required systemic therapy (itraconazole or dapsone), and all cases showed significant improvement within 2–10 months.
Figure 4A case of cutaneous leishmaniasis showing (a) a solitary crusted large nodule on the arm, (b) a non-caseating nodular granuloma in the mid dermis (H&E section, ×2), and (c) numerous intracellular amastigotes (Giemsa stain, ×100).
Eumycetoma (n = 12) presented as large plaques with an atrophic surface studded with multiple sinuses oozing pus in 10 cases (83.3%), while in two cases (16.7%) fungating masses with crusted surfaces were seen. All lesions were located on the lower limbs, especially the foot (Figure 5a) . Fungus colonies were detected by direct smear in three cases, by skin biopsy in seven cases (Figure 5b), and by tissue culture in two cases.
Figure 5A case of eumycetoma showing (a) a large plaque with atrophic surface studded with multiple sinuses on the lower leg, (b) a deep dermal granulomatous infiltrate with multiple colonies (H&E section, ×2), (c) Gram-negative staining (×20), and (d) periodic acid–Schiff-positive staining (×40).
Actinomycetoma (n = 9) presented clinically and pathologically as eumycetoma, but the fungal colonies of eumycetoma showed negative staining for Gram stain (Figure 5c), while colonies in both granulomas showed positive staining for PAS stain (Figure 5d).
Other rare granulomas included atypical Mycobacterium (three cases), schistosomiasis (two cases), and chromoblastomycosis (one case). Although skin biopsy was diagnostic in both Schistosomiasis cases and in the case of chromoblastomycosis, the diagnosis of atypical Mycobacterium was based mainly on tissue culture (two cases) and PCR (one case); the isolated organism was Mycobacterium marinum in all cases.
Atypical Mycobacterium presented clinically with erythematous nodules, followed by ulceration on the hands (two cases) and feet (one case); histologically they showed tuberculoid granulomas with variable degrees of central necrosis and prominent epidermal changes, mainly hyperkeratosis and ulceration. In all cases there was a conclusive history of injury during fish tank or swimming pool cleaning. These cases responded well to rifampin (6–16 weeks). A Schistosome granuloma was recorded in two cases, both of which presented with a solitary nodular lesion in the genital area, with histological features of a dense granulomatous reaction surrounding the Schistosome ovum in the mid-dermis. Chromoblastomycosis presented in one case with a verrucous mass in the elbow region; the histopathological features were grouped, rounded pigmented spores surrounded by a dense suppurative granulomatous infiltrate.
The exclusion of other non-infectious granulomas was done in a total of 69 cases. Sarcoidosis was the most common excluded granuloma, which was diagnosed in 51 cases: positive reticulum stain (45 cases), hilar lymphadenopathy and pulmonary fibrosis on chest X-ray, and hepatosplenomegaly by ultrasound (seven cases). A foreign body granuloma was diagnosed in 12 cases using a polarized microscope. Granuloma annulare was diagnosed in five cases by abundant mucin deposition, and granuloma multiforme (annular elastolytic granuloma) in one case by VVG stain that showed altered elastic tissue up to its absence.
4. Discussion
The spectrum of infectious granulomas in the Egyptian population has not been studied before, and there are no previous records concerned with the incidence or clinicopathological characteristics of such dermatoses in our community. Al-Hussein University Hospital is located in Cairo, the capital of Egypt, and is a tertiary referral center for many primary health centers in the surrounding governorates, which consist of mixed rural and urban areas of different social standards. Hence we believe that out study population is a real sector and a standard model for our community.
Our results demonstrate that the predominance of mycobacterial infections in our studied population, especially TB and leprosy, may represent a serious health hazard for Egyptians. It has been suggested that the incidence of TB in Egypt is underestimated, and the last national comprehensive tuberculin survey suggested that only two-thirds of actual cases are being identified by the national program.
TB treatment failure in Egypt has been attributed to non-compliance with treatment, deficient health education for the patient, poor patient knowledge regarding the disease, and diabetes mellitus as a co-morbid condition.
Lupus vulgaris was the most common form of cutaneous TB in our cases. The histological hallmark of LV is the formation of tubercles, which consist of accumulations of epithelioid histiocytes surrounded by a rim of lymphocytes and Langhans giant cells, with the presence or absence of caseation necrosis in the center.
World Health Organization. Report of the ninth meeting of the WHO Technical Advisory Group on Leprosy Control: Cairo, Egypt, 6–7 March 2008. Lepr Rev 2008;79:452–70.
However, these tubercles are not pathognomonic, and clinical criteria such as softness of the lesions, the brownish-red color, the slow evolution, and the apple-jelly nodules revealed by diascopy are important to suspect the diagnosis.
Although PCR was reported as a useful, rapid, and sensitive method for the detection of Mycobacterium tuberculosis DNA in formalin-fixed, paraffin-embedded specimens from LV and other forms of cutaneous TB, especially paucibacillary forms and those with non-classical clinical or histological presentation,
in: Freedberg I.M. Eisen A. Wolff K. Austen K.F. Goldsmith L.A. Katz S.I. Fitzpatrick T.B. Dermatology in general medicine. McGraw-Hill,
New York1999: 2274-2292
the diagnosis in many communities depends chiefly on clinical features, histopathological findings, and retrospective review of the response to treatment when the acid-fast bacilli cannot be found either by direct smear or culture.
Polymerase chain reaction based detection of Mycobacterium tuberculosis in tissues showing granulomatous inflammation without demonstrable acid-fast bacilli.
Leprosy formed the second most common form of infectious granulomas of the skin in this study. Although the annual new case detection of leprosy in Egypt decreased from 1412 in 2003 to 887 in 2007, the national program managers have expressed difficulties in deciphering actual decreases in cases and the results of missed diagnosis of leprosy cases, especially among general practitioners, for which there is a need to develop more efficient systems for confirming the diagnosis. The World Health Organization (WHO) Technical Advisory Group on Leprosy Control considers Egypt as one of five countries with the most significant leprosy burden in the Eastern Mediterranean region.
The diagnosis of leprosy depends mainly on the clinical examination of the skin and nerves. The disease may show different clinical presentations, ranging from well-defined plaques to ill-defined macules that can easily be misdiagnosed unless they are associated with marked sensory changes, alopecia, dryness, or diffuse infiltration.
The characteristic granulomatous infiltrate in the deep dermis, mainly around the adnexa, erector pili muscle, and more specifically around the neurovascular bundle, is the important diagnostic feature.
The presence of acid-fast bacilli in a biopsy and/or skin smears confirms the diagnosis of leprosy. In multibacillary leprosy, the histiocytes are usually rich with Mycobacterium leprae, thus posing no difficulty in the diagnosis, while in paucibacillary forms, the detection of lepra bacilli may be difficult, and in these cases they are rarely found in routine sections.
PCR was reported as a useful tool for rapidly detecting and quantifying M. leprae DNA in clinical specimens in which bacilli were undetectable by conventional histological staining.
Evaluation of real-time and conventional PCR targeting complex 85 genes for detection of Mycobacterium leprae DNA in skin biopsy samples from cases diagnosed with leprosy.
Infectious granulomas were studied in 515 cases in the Indian population, and mycobacterial infections were found to be the most common causative organisms (95.5%). Leprosy constituted the major granuloma group (72.4%), with a predominance of BT (55.2%). Cutaneous TB constituted the second most common group (23.1%), with a predominance of LV (50.4%). Fungal infections constituted 3.3% of the granulomas, while CL only formed 1.2%. Isolation of the infectious agent was achieved in 2.9% of BT, 5% of LV, 6.5% of scrofuloderma, and 50% of leishmaniasis, while the causative organism was isolated in all cases of BL, LL, and fungal infection. In contrast, M. leprae was not detected in any of the TT cases.
Cutaneous leishmaniasis was the third infectious granuloma in our cases. In Egypt, there are endemic foci of leishmaniasis that include several governorates, most of them surrounding the capital.
Zoonotic CL is now more frequently encountered and is gaining in importance as a health problem in Egypt. The rodent reservoir hosts are playing an important role in the dissemination and spread of the infection.
Although direct microscopy of scrapings taken from the margins of skin lesions is the most commonly used method for the diagnosis of CL, PCR is nowadays considered the most appropriate method in the diagnosis and for the identification of the species of CL, particularly in atypical and chronic cases, which may show low sensitivity for the conventional methods.
Comparing PCR with other traditional diagnostic techniques, it was found that PCR is the most sensitive single diagnostic test for CL, showing fewer false-negative results than the other methods.
Tissue culture has also been considered to be a feasible and gold standard diagnostic tool due to its high specificity, but it shows lower sensitivity than PCR. This may be attributed to potential contamination and the need for qualified technicians to perform the collection, preparation, preservation, and observation of the samples under field conditions.
Genus-specific kinetoplast-DNA PCR and parasite culture for the diagnosis of localised cutaneous leishmaniasis: applications for clinical trials under field conditions in Brazil.
The diagnosis of CL in endemic areas is usually based on the clinical presentation in addition to basic investigations (skin smear and biopsy), while the use of more sophisticated diagnostic techniques that allow for species identification is usually restricted to research or clinical settings in non-endemic countries.
The last of the common infectious granulomas in our cases was mycetoma, both fungal (eumycetoma 5.1%) and bacterial (actinomycetoma 3.9%). In this study, detection of the organism depended mainly on direct smear and skin biopsy. Although culture is important to differentiate between the types, we depended mainly on the histological criteria of the colonies and Gram stain. Granules of eumycetoma are composed of septate hyphae 4–5 μm thick, whereas the granules of actinomycetoma usually consist of fine, branching filaments or bacillary forms that are only about 1 μm thick.
Gram stain aids in differentiating bacterial from fungal causes of mycetoma; the filaments of actinomycetoma are Gram-positive, whereas the hyphae in grains of eumycetoma are Gram-negative.
The granules of both types are positively stained with PAS and GMS.
Evaluation of cases with a suspected mycetoma usually needs a constellation of findings, including a history of trauma, presence of the clinical triad (swelling, sinus tracts, and extrusion of grains), roentgenographic examination, histopathological study, examination of the grains, and culture.
This has been reported to be a simple, inexpensive, rapid, and sensitive technique that can be used in the routine diagnosis of mycetoma, in epidemiological surveys, and in material collection.
Serological diagnosis of mycetoma by ELISA has also been recommended as a routine test to confirm the diagnosis of Nocardia brasiliensis in human mycetoma cases.
Although schistosomiasis is a well-known endemic disease in Egypt, only two cases of Schistosome granuloma (cutaneous schistosomiasis) were diagnosed in this study. The manifestations of cutaneous schistosomiasis differ according to the stage – either invasive or oviposition. In the invasive stage, the lesions are non-specific anaphylactoid reactions associated with severe itching and generalized urticarial or erythema multiforme-like eruptions. In the oviposition stage, the lesions are specifically granulomatous and located away from the portacaval anastomoses, either genital, perigenital, or extragenital.
In conclusion, the pattern of infectious granulomas has not been fully studied in the Egyptian population and there is a lack of reports in the English language literature. We believe that infectious diseases form a common health problem in our community and that other multicenter studies are required for a more proper evaluation of this problem. Mycobacterial infections were found to be the most common cutaneous infectious granulomas in our study, and the clinicopathological diagnosis aided by special staining of direct smears or skin biopsy remains the most commonly applied and economical method for the routine diagnosis in developing countries. Tissue culture and PCR are costly techniques for routine use and their use may be more advocated for challenging cases and research purposes.
Acknowledgements
We thank Dr Saad edeen Muneir for medical photography, Dr Amany Abou-Bakr for help with the PCR, and Dr Hamid Mohamed for help with the tissue culture.
Funding: We declare that no funding existed for this study. The authors also certify that no sponsor limited the freedom of ideas, thoughts, or actions during the preparation of this study.
Ethical approval: This work was approved by the Scientific Committee of the Department of Dermatology and was performed according to the ethics guidelines of our university.
Conflict of interest: None of the authors have any conflict of interest to declare.
World Health Organization. Report of the ninth meeting of the WHO Technical Advisory Group on Leprosy Control: Cairo, Egypt, 6–7 March 2008. Lepr Rev 2008;79:452–70.
in: Freedberg I.M. Eisen A. Wolff K. Austen K.F. Goldsmith L.A. Katz S.I. Fitzpatrick T.B. Dermatology in general medicine. McGraw-Hill,
New York1999: 2274-2292
Polymerase chain reaction based detection of Mycobacterium tuberculosis in tissues showing granulomatous inflammation without demonstrable acid-fast bacilli.
Evaluation of real-time and conventional PCR targeting complex 85 genes for detection of Mycobacterium leprae DNA in skin biopsy samples from cases diagnosed with leprosy.
Genus-specific kinetoplast-DNA PCR and parasite culture for the diagnosis of localised cutaneous leishmaniasis: applications for clinical trials under field conditions in Brazil.
Corresponding Editor: Andy I.M. Hoepelman, Utrecht, the Netherlands.
Footnotes
☆Part of this work (4 years of the study) was presented as an abstract (poster) entitled “Clinicopathological and diagnostic study of cutaneous infectious granuloma in Egypt” at the XXXI Symposium of the International Society of Dermatopathology, Barcelona, Spain, October 2010.
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