Anti-phospholipid syndrome preceding a diagnosis of lepromatous leprosy
- Author(s): Kaliyadan, Feroze;
- Bhaskaran, M;
- Dharmaratnam A, D;
- Manoj, Jayasree;
- Sreekanth, G
- et al.
Published Web Locationhttps://doi.org/10.5070/D32g75646r
Anti-phospholipid syndrome preceding a diagnosis of lepromatous leprosyDepartment of Dermatology, Amrita Institute of Medical Sciences, Kochi, Kerala, India
Feroze Kaliyadan, Bhaskaran M, Dharmaratnam A D, Jayasree Manoj, Sreekanth G
Dermatology Online Journal 15 (6): 4
A 64-year-old male, with known anti-phospholipid syndrome (APS), which had been diagnosed two years previously, presented to our department with asymptomatic papules over his trunk. Histopathological examination confirmed the diagnosis of lepromatous leprosy. We present this as a case of APS, preceding a diagnosis of lepromatous leprosy.
A 64-year-old male patient presented to the dermatology department for asymptomatic papules over his trunk. The patient was known to have anti-phospholipid syndrome (APS), which had been diagnosed two years previously. He also had type 2 diabetes mellitus for which he was taking insulin. Other co-morbidities included hypertension, coronary artery disease, and dyslipidemia. The patient had been evaluated two years previously for suspected deep vein thrombosis associated with persistent thrombocytopenia and anemia. At that time anti-cardiolipin antibody IgM was strongly positive. All other hematological and autoimmune parameters were normal. Other relevant tests such as serological tests for syphilis, HIV, and HCV were also negative, as were investigations for tuberculosis. Based on the laboratory reports and the clinical features, he had been diagnosed with anti-phospholipid syndrome with associated thrombocytopenia.
|Figure 1||Figure 2|
|Figure 1. Infiltrated papules over the trunk|
Figure 2. Ear lobe infiltration
|Figure 3. Infiltrated papules over the forehead|
At the time of presentation to the dermatology department he had asymptomatic skin lesions mainly over the trunk and face of about two months duration. He was also complaining of persistent numbness affecting both lower legs (previously attributed to diabetic neuropathy). The patient did not complain of any other significant skin or mucosal lesions or of any muscle weakness. On dermatological examination we found infiltrated, erythematous papules mainly over the face and trunk (Figs. 1 - 3). There was significant infiltration of both ear lobes. There was no significant sensory loss over the lesions. No other significant skin and mucosal lesions were seen. The other significant clinical finding was a thickened right common peroneal nerve.
|Figure 4||Figure 5|
|Figure 4. Histopathology showing foamy macrophages (H&E, x40)|
Figure 5. AFB stain showing clumps of bacilli (x40)
The clinical features along with the previous diagnosis of APS strongly suggested the possibility of leprosy and the patient was investigated for the same. An acid-fast bacilli (AFB) smear from the ear lobes and the skin lesions demonstrated positivity for Lepra bacillus (Bacteriological index 4+, with the majority of bacilli showing solid staining).
A skin biopsy from one of the papules showed an atrophic epidermis with hyperpigmentation of the basal layer. A subepidermal Grenz zone was present. The papillary dermis showed a dense collection of macrophages with abundant vacuolated cytoplasm admixed with a few lymphocytes and epithelioid cells. The reticular dermis showed a dense collection of macrophages with destruction of pilar muscles, appendages, and nerve fibrils. A Wade-Fite staining demonstrated bacilli in the macrophages (Figs. 4 - 7). Based on the clinical features and laboratory findings, a diagnosis of lepromatous leprosy was made. The patient was started on multi-bacillary treatment for leprosy. However, considering the concomitant anemia and thrombocytopenia the patient was administered ofloxacin instead of dapsone. The patient has been under regular follow-up since and has shown significant symptomatic improvement.
|Figure 6||Figure 7|
|Figure 6. AFB stain showing clumps of bacilli (x100)|
Figure 7. AFB stain showing clumps of bacilli (x100)
Antiphospholipid antibodies (APLA) refers to autoantibodies found in relation to the anti-phospholipid syndrome (APS). These include mainly the anti-cardiolipin antibody (ACLA), and the anti β2 GPI (β2 Glycoprotein I). Antiphospholipid antibodies can be associated with a variety of clinical features such as deep venous thrombosis, arterial occlusive events, and recurrent fetal loss. Anti-phospholipid syndrome can occur as a primary form or secondary to autoimmune diseases or infections such as syphillis, HIV disease, Hepatitis C, and tuberculosis. The definite diagnosis of APS requires that a patient must meet at least one of the following clinical and laboratory criterion each .
- Vascular thrombosis - One or more clinical episodes of arterial, venous, or small vessel thrombosis in any tissue or organ confirmed by imaging studies, Doppler studies, or histopathology (without significant vessel wall inflammation)
- Pregnancy morbidity (normal morphology on ultrasonography or direct examination findings)
- One or more unexplained fetal deaths at more than 10 weeks gestation
- One or more premature births at less than 34 weeks gestation due to severe preeclampsia, eclampsia, or placental insufficiency
- Three or more unexplained consecutive spontaneous abortions at less than 10 weeks gestation, excluding maternal anatomic or hormonal abnormalities and paternal and maternal chromosomal causes.
- Anticardiolipin (aCL) antibody of the immunoglobulin G (IgG) /immunoglobulin M (IgM) isotype in medium/high titre (>40 IgG phospholipid units [GPL], >40 IgM phospholipid units [MPL], or >99th percentile) on two or more occasions at least 12 weeks apart (measured by a β2-GPI-dependent enzyme-linked immunosorbent assay [ELISA]).
- Lupus anticoagulant on two or more occasions at least 12 weeks apart
- Prolonged phospholipid-dependent coagulation (e.g., aPTT, Kaolin clotting time [KCT], dilute Russell viper venom test, dilute PT)
- Failure to correct the prolonged coagulation time by a mix with Platelet Poor Plasma (PPP)
- Shortening or correction of the prolonged coagulation time with excess phospholipid
- Exclusion of other coagulopathies (e.g., factor VIII inhibitor, factor V Leiden, heparin)
Leprosy is another infection, which is known to be associated with APS. Most studies show the predominance of an IgM sub-type of APLA in leprosy [2, 3, 4]. The present view of APS in leprosy is that the APLA in leprosy can also induce thrombotic changes; some of the leprosy associated APLA are co-factor β2 GPI dependent, which promotes binding to blood vessel phospholipids, as in autoimmunity associated APS. Previously, it was thought that leprosy-associated APS was β2 GPI independent and hence not associated with thrombotic phenomenon; the binding of autoimmune APLA to phospholipid is enhanced by the cofactor β2 GPI [5, 6, 7]. Accordingly there have been reports suggesting the role of APLA in inducing gangrenous changes in leprosy patients .
The interesting feature in our case was the development of signs and symptoms of leprosy two years after the development of the features of APS. We hypothesize that considering the long incubation period of leprosy, the leprosy bacilli might have been present in the patient's body prior to the development of APS and could have triggered the APS. Another important corollary we would like to highlight is that a patient presenting with features consistent with APS and who has no other apparent cause for the same, should be investigated for leprosy, especially in an endemic area.
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