Ikram Ullah khan

November 27, 2018Ikram Ullah khanCase Studies - Best dermatologist in Islamabad Prof. Dr. Ikram Ullah Khan

Case Report – Granuloma Formation in Discoid Lupus Erythematosus: A Novel Microscopic Feature

Rifat Yasmin, Prof. Dr. Ikramullah Khan, Anwar Ul Haque, Syed Afaq Ahmad
Pakistan Institute of Medical Sciences, Islamabad : Sebaceous Granuloma Formation in Discoid Lupus Erythematosus

Abstract

Background: Lupus erythematosus is an autoimmune disease with diverse manifestations. When multiple systems are involved, it is termed systemic lupus erythematosus (SLE), while exclusive skin involvement is referred to as discoid lupus erythematosus (DLE). Periappendageal inflammation is a recognized histopathological feature of DLE, which can lead to the formation of sebaceous granulomas.

Objective: This study aims to determine the frequency of sebaceous granuloma formation in discoid lupus erythematosus.

Materials and Methods: A prospective observational study was conducted at Pakistan Institute of Medical Sciences, Islamabad. Over a span of two years, we examined 100 cases of DLE. We assessed histopathological features, including sebaceous granulomas, along with other common indicators of DLE.

Results: Out of 100 cases, 8 exhibited sebaceous granulomas. These granulomas contained epithelioid cells, foreign body giant cells with digested sebaceous material, and lymphocytes.

Conclusion: Our findings highlight the presence of sebaceous granulomas in 8% of DLE cases. This unique feature must be understood by both dermatologists and pathologists to ensure accurate diagnosis and prevent misinterpretation due to the presence of granulomas.

Introduction

Discoid lupus erythematosus (DLE) is a chronic, atrophic, photosensitive skin disease. While DLE can coexist with systemic lupus erythematosus (SLE), they differ in severity and systemic involvement. DLE primarily affects the skin, and its primary lesion is an erythematous papule or plaque. Patients with DLE rarely fulfill criteria for SLE. Additionally, serologic abnormalities are uncommon. Nonetheless, treatment with sunscreens, topical corticosteroids, and antimalarial agents has proven effective. This study delves into a previously undescribed histopathological feature of DLE – the presence of sebaceous granulomas. These granulomas result from intense chronic periappendageal inflammation, which ultimately leads to the destruction of sebaceous glands.

Materials and Methods

For this observational study, we examined 100 DLE cases spanning two years. Our aim was to evaluate the presence of sebaceous granulomas, in addition to assessing other common histopathological features like hyperkeratosis, epidermal atrophy, perivascular inflammation, and collagen damage.

Results

Among the 100 cases, 8 cases exhibited sebaceous granulomas. These granulomas were characterized by epithelioid cells, foreign body-type giant cells, and lymphocytes. Furthermore, we observed typical features of DLE, such as hyperkeratosis, epidermal atrophy, and collagen damage.

Discussion

DLE can lead to various complications, including scarring, hair loss, and hyperpigmentation if not treated promptly. Its prevalence varies, affecting around 17 to 48 individuals per 100,000 people, with a higher incidence in women compared to men. DLE falls within the broader lupus spectrum, with DLE primarily affecting the skin and SLE involving multiple organs. Subacute cutaneous lupus erythematosus (SCLE) lies between these two extremes. In our study, we identified sebaceous granulomas as an important feature of DLE. These granulomas may originate from lipid destruction within sebaceous glands. The presence of lipid might initiate granuloma formation, a phenomenon observed in various contexts, including infections and foreign body reactions. Further investigation is warranted to understand the clinical implications of this unique finding.

Conclusion

In conclusion, our study revealed sebaceous granuloma formation in 8% of DLE cases. Recognizing this distinct feature is vital for dermatologists and pathologists alike. It ensures accurate diagnosis, preventing misinterpretation due to the presence of granulomas, and contributes to improved patient management and outcomes.

Address for Correspondence:

Dr. Rifat Yasmin, Department of Dermatology, Pakistan Institute of Medical Sciences, Islamabad. E-mail: rifat_chaudhary@yahoo.com

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November 27, 2018Ikram Ullah khanCase Studies - Best dermatologist in Islamabad Prof. Dr. Ikram Ullah Khan

Comparative Analysis of Treatment Response in Cutaneous Leishmaniasis: Intralesional Chloroquine vs. Intralesional Meglumine Antimoniate

Authors: Rifat Yasmin, Ikramullah Khan, Syed Afaq Ahmad
Affiliation: Pakistan Institute of Medical Sciences, Islamabad

Abstract

Background: Cutaneous leishmaniasis (CL), primarily caused by Leishmania major, is a prevalent condition in Pakistan. For cases involving simple lesions, localized treatments such as intralesional antimony compounds hold significance. This study aims to systematically compare the efficacy of intralesional chloroquine with meglumine antimoniate in treating CL.

Objective: The primary objective of this research is to evaluate and systematically compare the therapeutic outcomes of intralesional chloroquine and intralesional meglumine antimoniate in the treatment of CL.

Patients and Methods: Conducted as a quasi-experimental study, this research included 60 patients aged over 3 years with 1 to 3 CL lesions. Patients were categorized into two groups: the intralesional chloroquine treatment group and the intralesional meglumine antimoniate control group. Both treatment modalities were administered once weekly for 8 weeks, with a dosage of 1cc per cm2 of lesion. Additional injections were administered to patients showing partial response.

Results: Both treatment strategies exhibited a robust 100% response rate. However, the meglumine antimoniate group required a notably higher number of injections compared to the chloroquine group (p<0.05). Notably, both drugs were well-tolerated by the patients.

Conclusion: Intralesional chloroquine emerges as an effective, safe, and cost-efficient alternative to meglumine antimoniate for the treatment of CL.

Keywords: Cutaneous leishmaniasis, intralesional, chloroquine, meglumine antimoniate

Introduction

Despite considerable progress in the treatment and control of cutaneous leishmaniasis (CL), the disease remains a significant public health concern, particularly in regions like Afghanistan, Iran, Iraq, Algeria, Saudi Arabia, Peru, and Pakistan. The World Health Organization (WHO) identifies leishmaniasis as endemic in 88 countries, posing a risk to around 350 million people globally. While most CL lesions resolve on their own, intervention is warranted in specific cases such as early-stage lesions, multiple lesions, cosmetically sensitive areas, mucosal involvement, and immunosuppression. The dual therapeutic goals encompass both clinical healing and parasite eradication. However, finding effective, accessible treatments remains a challenge. While pentavalent antimony compounds remain the primary treatment approach, they exhibit concerns related to toxicity and resistance. This study investigates the potential of intralesional chloroquine as an alternative treatment modality.

Materials and Methods

Conducted at the Department of Dermatology, Pakistan Institute of Medical Sciences, Islamabad, this quasi-experimental study enrolled patients aged over 3 years with 1 to 3 lesions. Patients with lesions exceeding 5 cm, those undergoing concurrent antileishmaniasis treatment, and pregnant individuals were excluded. The patients were allocated into two groups: the intralesional chloroquine (Group A) and intralesional meglumine antimoniate (Group B) groups. Both groups received 8 weekly injections (1cc per cm2 of lesion). Patients showing partial response received additional injections.

Results

Of the 60 patients enrolled, each group consisted of 30 individuals. Both treatment modalities achieved an impressive 100% response rate. However, the meglumine antimoniate group necessitated a significantly higher number of injections compared to the chloroquine group (p<0.05). Notably, both drugs were well-tolerated, with no significant adverse effects reported.

Discussion

While traditional antimony compounds are effective, they are constrained by their toxicity and the emergence of resistance. This study underscores that intralesional chloroquine serves as an effective and well-tolerated treatment modality for CL. The 100% response rate after 8 injections demonstrates its therapeutic potential. Moreover, chloroquine’s minimal side effects, cost-effectiveness, and accessibility in resource-limited settings further bolster its appeal. A comparative analysis of the two treatment groups highlights chloroquine’s superiority in terms of both efficacy and safety.

Conclusion

Intralesional chloroquine offers a promising alternative to existing CL therapies. Its high efficacy, minimal side effects, cost-effectiveness, and wide availability make it a valuable addition to the treatment arsenal against cutaneous leishmaniasis. This study contributes substantial evidence supporting the use of intralesional chloroquine as an effective and feasible treatment option.

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November 27, 2018Ikram Ullah khanCase Studies - Best dermatologist in Islamabad Prof. Dr. Ikram Ullah Khan

nternational Journal of Pathology; 2010; 8(1): 22-25 22
Original Article

Sebaceous Granulomas: A Novel Feature of Discoid                                          Lupus Erythematosus

 Rifat Yasmin, Dr. Ikramullah Khan, Anwar Ul Haque, Syed Afaq Ahmad

Objective: To determine the frequency of sebaceous granulomas formation in discoid lupus erythematosus.
Study Design: Retrospective observational study.
Setting: Departments of Dermatology and Pathology, Pakistan Institute of Medical Sciences, best skin specialist in islamabad.
Material and Methods: 100 cases of Discoid Lupus Erythematosus (DLE)spanning over two years and with the age range of 3 years to 70 years were examined for the presence of Sebaceous Granuloma. Other features of DLE like hyperkeratosis, follicular plugging, epidermal atrophy, basal layer vacuolization, basement membrane deposits, pigmentary incontinence, perivascular inflammation, periappendigeal inflammation, and collagen damage were also noted.
Introduction: Lupus erythematosus is an immune complex, type III hypersensitivity disease where antibodies are formed against native Deoxyribose Nucleic Acid (DNA). The immune compexes are deposited in various organs and various sites causing marked pleotropism. If several systems are involved then the disease is named Systemic Lupus Erythematosus (SLE) and if skin is exclusively involve the term Discoid Lupus Erythematosus (DLE) is used. One of the several features of DLE includes periappengeal inflammation. This may at times completely wipe out sebaceous glands forming sebaceous granulomas.
Results: Out of these 100 cases 8 cases contained sebaceous granulomas. These granulomas were composed of epithelioid cells, foreign body giant cells containing partially digested sebaceous material and a few lymphoctytes.
Conclusion: Sebaceous granulomas formation was seen in 8 % cases of discoid lupus erythematosus. This feature must be recognized both by dermatologists and pathologist so that diagnosis of DLE may not be distracted and erroneous diagnosis due to presence of granulomas may not be rendered.
Key Words: Discoid lupus erythematosus (DLE), Systemic Lupus Erythematosus (SLE), periappendageal inflammation, chronic granulomatous inflammation, sebaceous granulomas.

Introduction:

Discoid lupus erythematosus (DLE) is a chronic, scarring, atrophy producing, photosensitive dermatosis. Discoid lupus erythematosus may occur in patients with systemic lupus erythematosus (SLE), and some patients (<5%) with discoid lupus erythematosus progress to SLE.¹ Some patients also have the lesions of subacute cutaneous lupus erythematosus (SCLE), and some may have a malar rash. Discoid lupus erythematosus lesions (DLE) are frequently fairly characteristic. The primary lesion is an erythematous papule or plaque with slight-to-moderate scaling. As the lesion progresses, the scale may thicken and become adherent, and pigmentary changes may develop. Patients with discoid lupus erythematosus rarely fulfil four or more of the criteria used to classify SLE.²Serologic abnormalities are uncommon.³ Therapy with sunscreens, topical corticosteroids, and antimalarial agents is usually effective. This study was based on hitherto undescribed sebaceous granulomas as a feature of DLE in some cases which we observed in our weekly dermatopathological conference held in our institution. The sebaceous granulomas are apparently formed due to destruction of sebaceous glands from intense chronic periappendigeal inflammation. The liberated lipid and fat vacuoles initiate and promote phagocytic activity, epithelioid cell differentiation and giant cell formation finally culminating into well formed granulomas. This feature was of course not seen in all cases but observed in some cases. The purpose of this  study was to determine the frequency of the sebaceous granulomas and to create awareness among dermatologists and pathologists about this feature which may otherwise lead to erroneous diagnoses.

Materials and Methods

This prospective descriptive study was carried out at Pathology Department of Pakistan Institute of Medical Sciences(PIMS) based on our observations in weekly Dermato-Pathological conferences. 100 cases of DLE patients of both gender and age range of 3 years to 70 years, spanning over two years period were examined specifically for the presence or absence of well formed sebaceous granulomas. All cases with the clinical suspicion of cutaneous LE were biopsied, which were routinely processed and stained in the department of pathology using formalin fixation and hematoxylin and eosin (H&E) staining. The slides were seen jointly in the weekly Dermatopathology session held every Friday together with consultant pathologist along with the whole dermatology department on multihead microscope attached with TV monitors and overhead projector. We observed that along with usual hyperkeratosis, follicular plugging, epidermal atrophy, basal layer vacuolization, basement membrane deposits, pigmentary

incontinence perivascular inflammation, periappendigeal inflammation, and collagen damage, some cases had complete replacement of the sebaceous glands with their replacement with well formed sebaceous granulomas. All such cases were studied in detail toward composition and  characteristic granulomas.

Results

Out of these 100 cases, 8 casescontained sebaceous granulomas. The cases were associated with absence of normal sebaceous glands. Remnants of hair follicles and/or erector pylorum muscles provided the clue to the true nature of the granulomas. These granulomas possessed macrophages containing large lipid vacuoles derived from sebaceous glands. Some of these macrophages converted into Langhan’s type multinucleated giant cells. (Figure I and II)
Other histopathological features included hyperkeratosis, keratin plugging, epidermal atrophy, basal cell vacuolization, perivasuclar inflammation, and collagen damage.(Table I)

Table : I Frequency Table of histopathological features of patients

Discussion

Discoid lupus erythematosus is a chronic dermatological disease that can lead to scarring, hair loss, and hyperpigmentation changes in the skin if it is not treated early and promptly1 . It has a prolonged course and can have a considerable effect on quality of life. The prevalence is between 17 and 48 per 100,000 people. Women are affected about twice as often as men, compared with 10 times the frequency for SLE. The usual age of onset is between 20 and 40 years, which is about 20 years younger than SLE. Lupus erythematosus (LE) is thought to be an autoimmune disease which belongs to a group of connective tissue diseases like scleroderma, rheumatoid arthritis, polymyositis, and mixed connective tissue disease. Within the spectrum of diseases included in LE, at one end is a disease confined mainly to the skin and referred to as discoid lupus erythematosus (DLE) and at the other end is a florid disease with systemic involvement of heart, lungs, brain, kidneys and other organs called systemic lupus erythematosus (SLE). In between the two ends of the spectrum are disorders like subacute cutaneous lupus. Subacute cutaneous lupus erythematosus (SCLE) has a rather sudden onset with annular or psoriasiform plaques erupting on the upper trunk, arms, and/or dorsa of hands, usually after exposure to sunlight1. Although at the benign end of the spectrum, 1% to 5% of patients with discoid lupus may develop SLE and 25% of patients with SLE may develop typical chronic discoid lesions at some time during the course of their illness.2 Lupus occurs in all age groups with a mean age varying from 21 to 50 years1,2 and a prevalence of 17 to 48 in 100,000, with a greater prevalence in AfroCaribbean people. Although LE is an autoimmune disease, it is thought to result from interplay of certain genetic factors, environmental factors like ultraviolet light, and hormonal factors with antibodies.3 Early recognition and treatment improves the prognosis. The diagnosis is usually made by clinical examination. In some cases histopathology3 may be required to confirm the diagnosis. The histology is that of a lichenoid tissue reaction with changes at the dermo-epidermal junction that include thickening of the basement membrane (best demonstrated by periodic acid-Schiff staining) and vacuolar degeneration of the basal cells along with perivascular and periappendigeal inflammatory cell infiltration of a variable degree in the reticular dermis. Hyperkeratosis is more evident and follicular plugging may be seen in more mature lesions.4,5 DLE tends to run a less severe course than SLE and has a better prognosis.6 It is important for family physicians to recognize DLE because it is a potentially scarring disease. Early referral and institution of treatment by dermatologists increases the hope of minimizing the progression of the disease and consequent socioeconomic impact on the individual. There is insufficient evidence for the effective treatment. Because lesions are induced or exacerbated by ultraviolet exposure, photoprotective measures are important. Potent topical steroids and antimalarials are the mainstay of treatment. Some cases of discoid lupus erythematosus can be refractory to standard therapy; in these cases retinoids, thalidomide7 , and topical tacrolimus8 offer alternatives, as do immunosuppressives like azathioprine, cyclosporine, mycophenolate mofetil, and methotrexate.9 The histopathological features observed in discoid lupus erythematosus include vacuolar alteration of the basal cell layer, thickening of the basement membrane, follicular plugging, hyperkeratosis, atrophy of the epidermis, incontinence of pigment, and inflammatory cell infiltrate (usually lymphocytic) in a perivascular, periappendigeal, and sub epidermal location. Often, an abundance of mucin is seen within the dermis.10 The histopathological features differ depending upon the type and age of the lesion.11 In this study histopathological features were having hyperkeratosis, basal cell damage and collagen damage as most common features with presence in 100% of cases. Epidermal atrophy was seen in 97% of cases and periappendigeal and perivascular inflammation in 96% and 94% of patients respectively. Acanthosis was found in 40% of cases. Parakeratosis was the least found feature with percentage of only 20. (Table I) Total number of cases which were examined over period of two years was 100. Out of these 100 cases 8 cases showed formation of sebaceous granulomas.This finding has not previously been discussed much with the histopathological findings of discoid lupus erythematosus. Another important finding in this study was the earlier destruction of sebaceous glands than hair follicle. This was shown in the form of lymphocytic infiltration of sebaceous glands, disruption of glandular structure and formation of sebaceous granulomas comprising foreign body giant cells as well as partially digested sebaceous material. Skin is host to many different types of granulomas.12 Like tuberculosis and leprosy where the lipid coat of the Mycobacterium serve as an inciting factor, lipid of sebaceous gland may lead to granulomas formation. Granuloma formation may result from simple hemorrhages in some cases. (Cholesterol granuloma)13. Apart from infectious agents such as Leishmania Donovani bodies and Fungi, dead hair and myriad of foreign bodies may result in granuloma formation. Endogenous substances such as mammary gland secretions (granulomatous mastitis), sperm (spermatocytic granuloma), dead or damaged collagen (granuloma Annulare, cutaneous laxa) may result in granulomas formation. 14 Endogenous Hemorrhages (giant cell Tumour of bone) and in present study lipid of sebaceous glands may cause granuloma formation. Evaluation of each and every microscopic feature is necessary to further delineate the etiology and clinical course of the disease.15 More studies are needed to evaluate the changes on larger scale as this might be having some relationship to the duration or severity of clinical features of DLE and may be helpful in the treatment and prognosis of these patients.

Conclusion

Sebaceous granuloma formation is an important dermatopathological finding which can be occasionally encountered in DLE. Sebaceous glands seem to be destroyed earlier than the hair follicles and hence persisting hair follicles and erector pylorum muscle may provide a clue to the true nature of sebaceous granulomas. Both dermatologists and pathologists must be aware of this infrequent feature (8% in our study) in order not to be distracted from the diagnosis of DLE and from rending an erroneous diagnosis based on the granulomas.

References

1. Fabbri P, Cardinali C, Giomi B, Caproni M. Cutaneous lupus erythematosus: diagnosis and management. Am J Clin Dermatol 2003; 4: 449–65.

2. Weber F, Schmuth M, Fritsch P, Sepp N. Lymphocytic infiltration of the skin is a photosensitive variant of lupus erythematosus: evidence by phototesting. Br J Dermatol. 2001;144:292–296.

3. Crowson AN, Magro C. The cutaneous pathology of lupus erythematosus: a review. J Cutan Pathol. 2001;28:1–23.

4. Baima B, Sticherling M. Apoptosis in different cutaneous manifestations of lupus erythematosus. Br J Dermatol. 2001;144:958–966.

5. Parodi A, Caproni M, Cardinali C, et al.. Clinical, histological and immunopathological features of 58 patients with subacute cutaneous lupus erythematosus. Dermatology. 2000;200:6– 10.

6. Callen JP. Cutaneous lupus erythematosus: a personal approach to management. Australas J Dermatol. Feb 2006;47(1):13‐27.

7. Housman TS, Jorizzo JL, McCarty MA, Grummer SE, Fleischer AB Jr, Sutej PG. Low‐dose thalidomide therapy for refractory cutaneous lesions of lupus erythematosus. Arch Dermatol. Jan 2003;139(1):50‐4.

8. Heffernan MP, Nelson MM, Smith DI, Chung JH. 0.1% tacrolimus ointment in the treatment of discoid lupus erythematosus. Arch Dermatol. Sep 2005;141(9):1170‐ 1.

9. Wenzel J, Brahler S, Bauer R, Bieber T, Tuting T. Efficacy and safety of methotrexate in recalcitrant cutaneous lupus erythematosus: results of a retrospective study in 43 patients. Br J Dermatol. Jul 2005;153(1):157‐62.

10. AL,   Venketaram   MN,  Bhushnurmath  SR.Cutaneous lupus erythematosus:comparison of direct immunofluorescencefindings with histopathology.Int J Dermatol.1995;34:480‐2.

11. Jerdan MS, Hood AF, Moore GW, Callen JP. Histopathologic comparison of the subsets lupus erythematosus.Arch Dermatol 1990;126:52‐5.

12. Qureshi R, Shaikh R and Haque AU. Chronic granulomatous inflammatory disorders of skin at a tertiary care hospital in Islamabad. Int J Pathol 2004; (2) 31‐34

13. Haque AU In Situ hemorrhage Int. J Pathology 2003 (1) 60

14. Saeed M and Haque AU. Cutaneous laxa with granulomatous inflammation Int.J. Pathol 2008; 6 (2) 86‐90

15. Moatasim A and Haque AU The value of individual microscopic features in diagnosis of cutaneous lupus erythematosus. Int J Pathol 2005 3; 76‐80.

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