Mucocutaneous manifestations of COVID-19-associated mucormycosis: A retrospective cross-sectional study.

Background Cutaneous mucormycosis has shown a significant upsurge during the COVID-19 pandemic. Due to the rapid progression and high mortality of cutaneous mucormycosis in this context, it is important to identify it early. However, very few studies report detailed clinical descriptions of cutaneous mucormycosis in COVID-19 patients. Objectives To describe mucocutaneous lesions of COVID-19-associated mucormycosis based on clinical morphology and attempt to correlate them with radiological changes. Methods A retrospective cross-sectional study was conducted at a tertiary care centre from 1st April to 31st July 2021. Eligibility criteria included hospitalised adult patients of COVID-19-associated mucormycosis with mucocutaneous lesions. Results All subjects were recently recovering COVID-19 patients diagnosed with cutaneous mucormycosis. One of fifty-three (2%) patients had primary cutaneous mucormycosis, and all of the rest had secondary cutaneous mucormycosis. Secondary cutaneous mucormycosis lesions presented as cutaneous-abscess in 25/52 (48%), nodulo-pustular lesions in 1/52 (2%), necrotic eschar in 1/52 (2%) and ulcero-necrotic in 1/52 (2%). Mucosal lesions were of three broad sub-types: ulcero-necrotic in 1/52 (2%), pustular in 2/52 (4%) and plaques in 1/52 (2%). Twenty out of fifty-two patients (38%) presented with simultaneous mucosal and cutaneous lesions belonging to the above categories. Magnetic resonance imaging of the face showed variable features of cutaneous and subcutaneous tissue involvement, viz. peripherally enhancing collection in the abscess group, "dot in circle sign" and heterogeneous contrast enhancement in the nodulo-pustular group; and fat stranding with infiltration of subcutaneous tissue in cases with necrotic eschar and ulcero-necrotic lesions. Limitations The morphological variety of cutaneous mucormycosis patients in a single-centre study like ours might not be very precise. Thus, there is a need to conduct multi-centric prospective studies with larger sample sizes in the future to substantiate our morphological and radiological findings. Conclusions COVID-19-associated mucormycosis patients in our study presented with a few specific types of mucocutaneous manifestations, with distinct magnetic resonance imaging findings. If corroborated by larger studies, these observations would be helpful in the early diagnosis of this serious illness.

Laboratory perspectives for Leprosy: Diagnostic, prognostic and predictive tools.

The diagnosis of leprosy poses several challenges. The bacillary load, serology, and tissue response are determined by the host immune status, which make individual tests unsuitable across the spectrum. The sensitivity of tests for identifying paucibacillary cases remains limited, on the other hand, many tests lack specificity in differentiating contacts from diseased cases. Nonetheless, a plethora of laboratory tests have been added to the armamentarium of the clinicians dealing with leprosy. In the current review, we critically analyze the tests available for diagnosis, prognostication, and prediction of treatment response in leprosy. We discuss in brief the conventional tests available and detail the newer serologic and molecular tests added over the past few years with an attempt to suggest the pros and cons of each, and the tests best fit for each clinical scenario. Slit skin smears and skin or nerve biopsies are primarily performed to exclude clinical mimics, confirm a diagnosis, and immunologically subtype the case. Antibody titres of phenolic glycolipid-1 and its synthetic variants can be measured in serum and saliva and provide noninvasive means to detect leprosy with good specificity. Conventional, quantitative, real-time, and other variants of PCR can detect M. leprae DNA and have been used to effect in blood, tissue, and urine samples. T helper I and II cytokine signatures can be used to differentiate the subtypes of leprosy. Newer machine learning algorithms use combinations of these tests to predict the development of leprosy in contacts. Tests to detect treatment response, antimicrobial drug resistance, and predict the onset of reactions in leprosy can be used to advantage. We compare the characteristics of these tests and suggest an algorithm for leprosy diagnosis optimally utilizing them in various clinical settings.

Unusual non-trophic ulcerations in leprosy: A case series of 17 patients.

Non-neuropathic ulcers in leprosy patients are infrequently seen, and atypical presentations are prone to misdiagnosis. We evaluated diagnosed cases of leprosy between January 2017 and January 2020 for the presence of cutaneous ulceration, Ridley-Jopling subtype of leprosy, reactions and histologic features of these ulcerations. Treatment was given as WHO recommended multi-bacillary multi-drug therapy. We found 17/386 leprosy patients with non-neuropathic ulcers. We describe three causes - spontaneous cutaneous ulceration in lepromatous leprosy (one nodular and one diffuse), lepra reactions (five patients with type 1; nine with type 2, further categorised into ulcerated Sweet syndrome-like who also had pseudoepitheliomatous hyperplasia, pustulo-necrotic and necrotic erythema nodosum leprosum) and Lucio phenomenon (one patient). Our series draws attention towards the different faces of non-neuropathic ulcers in leprosy, including some atypical and novel presentations.

Cyclooxygenase 2 and vascular endothelial growth factor-potential targets to manage lepra reactions: A case-control study.

Reactions in leprosy have an immune mediated pathogenesis. While type 1 reactions are delayed hypersensitivity phenomenon, type 2 reactions are immune complex mediated. Key molecules which mediate the immune insult in lepra reactions require evaluation in order to tailor their therapy and prevent disability. The objective of the study was to evaluate expressions of Cyclooxygenase 2 and Vascular Endothelial Growth Factor in skin biopsies from leprosy patients and correlate their expression with presence of either type 1 or type 2 lepra reactions. This was a case control study. Cyclooxygenase 2 and Vascular Endothelial Growth Factor expression in dermal macrophages and vascular endothelium was assessed immunohistochemically. Biopsies from patients with Non-reactive leprosy and healthy controls were used for comparison. SPSS software was used for statistical analysis. A total of 147 skin biopsies were evaluated, including 18 with Type 1 reaction, 39 Type 2 reaction, 81 non-reactive leprosy and 9 healthy controls. Both Cyclooxygenase 2 and Vascular Endothelial Growth Factor expression were significantly higher in type 1 followed by type 2 reaction as compared to controls. These results may guide us regarding use of Cyclooxygenase 2 and Vascular Endothelial Growth Factor inhibitor drugs which may be a major step in treating reactive leprosy patients and preventing nerve damage and disability.

Mandating nerve biopsy: A step towards personalizing therapy in pure neuritic leprosy.

Pure neuritic leprosy (PNL) accounts for 5% to 10% of leprosy patients who usually present with asymmetrical neuropathy in the absence of lepra bacilli on slit-skin smears. However, nerve biopsies in PNL lack appropriate categorization in current immunologic terms. We aimed to classify nerve biopsies according to the immune spectrum of leprosy and assess the role of histologic classification of nerve biopsies in treating PNL. Patients from two tertiary care referral centres were enrolled in this incident case study. Patients presenting with mononeuropathy and multiple mononeuropathies presumably with leprosy, without skin lesions, underwent nerve biopsy and slit-skin smear examination. Amongst 78 patients with mononeuropathy, 38 were diagnosed with leprosy on nerve biopsy. Leprosy was classified as tuberculoid in 16, lepromatous in 5 and borderline in 17 patients. Lepra bacilli were present in 15 biopsies. On comparing histologic subtypes with number of nerves involved clinically, a significant number of cases with single nerve involvement showed multibacillary (BB, BL or LL) histology and vice versa. Nerve biopsy helps in diagnosing patients presenting with PNL and aids in classifying it to customize the treatment for best results. Current treatment recommendations for PNL from WHO and National Leprosy Eradication Program are based on clinical assessment only, which are likely to result in inconsistent treatment and possibly relapse in cases where histomorphology shows disparity. Inclusion of nerve biopsy to guide therapy in patients with PNL is suggested.

Nerve biopsy in Indian patients with mononeuropathy multiplex of undetermined etiology.

INTRODUCTION: A diagnosis of mononeuropathy multiplex (MM) requires detailed evaluation to determine etiology. We performed nerve biopsy on patients with MM in whom the etiology could not be established via other investigations. METHODS: Sixty-eight patients with MM seen between January 2013 and June 2014 underwent detailed diagnostic evaluation. Those in whom the investigations failed to establish an etiology underwent nerve biopsy. RESULTS: A diagnosis of leprosy was confirmed in 14 patients and was highly probable in 17 others. Eleven patients had vasculitic neuropathy, and in 1 patient there were amyloid deposits on nerve biopsy. CONCLUSIONS: In 43 of 68 Indian patients (63%) with MM, nerve biopsy identified a definite (26 patients) or probable (17 patients) etiology. Nerve biopsy is a valuable investigation in MM that frequently results in a diagnosis of leprosy in India. Muscle Nerve, 2016 Muscle Nerve 55: 23-27, 2017.

Comprehensive electrophysiology in leprous neuropathy - Is there a clinico-electrophysiological dissociation?

OBJECTIVE: The diagnosis of leprous neuropathy is mostly empirical and electrophysiological studies may not truly represent the clinical findings. This study comprehensively evaluates the neuroelectrophysiology and looks at clinico-electrophysiological dissociation. METHODS: Conventional electrophysiological recording included evaluation of median, ulnar, radial, tibial, and common peroneal nerve; an extended protocol included great auricular, phrenic, and facial nerves, along with sympathetic skin response and blink reflex. Nerve biopsy and slit skin smear were done to aid categorization. RESULTS: Forty-six patients of leprosy were enrolled. Mononeuritis multiplex was the commonest presentation. Sensory loss was commoner than motor deficits. Approximately 60% of all cases were nerve-biopsy proven. Nerve thickening was present in 38.7% (214/552) of nerves examined. Clinico-electrophysiological dissociation between nerve thickening and nerve conduction findings was present in median, ulnar, great auricular, and common peroneal nerves. CONCLUSION: Electrophysiological findings outnumber occurrence of nerve thickening and clinical deficits in leprous neuropathy. From a clinical perspective, enlargement of great auricular, ulnar, and common peroneal nerves may be more sensitive in predicting electrophysiological abnormalities. SIGNIFICANCE: A comprehensive nerve conduction study including great auricular and phrenic nerves, coupled with a sympathetic skin response, may aid in detecting cases with paucity of findings since such a combination is seldom seen in other disorders.

Nerve abscess in primary neuritic leprosy.

Nerve abscess is an infrequently reported complication of leprosy. We describe a patient with a pure neuritic type of leprosy with multiple nerve abscesses, who presented with tingling and numbness in the medial aspect of his right forearm and hand. Subsequently he developed pain, redness and swelling over the medial side of his right elbow and the flexor aspect of his right wrist. High-resolution ultrasound showed diffuse thickening of the right ulnar nerve with hypoechoic texture housing a cystic lesion with internal debris suggesting an abscess, at the cubital tunnel. Histopathological examination of the pus and tissue obtained from the abscess revealed presence of granulomas with lepra bacilli. The patient responded to surgery and multidrug therapy. In conclusion, the nerve abscess as the first manifestation of leprosy is uncommon and a high index of suspicion is required to make a correct diagnosis.