{"id":1518,"date":"2020-03-21T15:55:48","date_gmt":"2020-03-21T15:55:48","guid":{"rendered":"https:\/\/haema-journal.gr\/?p=1518"},"modified":"2020-03-23T22:33:11","modified_gmt":"2020-03-23T22:33:11","slug":"bone-marrow-changes-in-hiv-infection","status":"publish","type":"post","link":"https:\/\/haema-journal.gr\/?p=1518","title":{"rendered":"Bone marrow changes in HIV infection"},"content":{"rendered":"

Haema 2019; 10(2):66
\n<\/em><\/p>\n

Konstantinos Liapis<\/p>\n

Consultant Haematologist, Georgios Gennimatas Hospital<\/p>\n

Full PDF<\/a> | \"\"<\/a><\/p>\n

<\/p>\n

HIV\/AIDS is common in the tropics: HIV prevalence is very high in tropical Africa (1-15%), extremely high in South Africa and Botswana (18-20%), and 3.3% in some Caribbean countries (Haiti, Barbados). HIV prevalence is also high in parts of South-East Asia. Thus, HIV has emerged as a major cause of morbidity and mortality in many tropical countries. In many hospitals in East and Southern Africa, over half of all inpatients are infected with HIV, most suffering from complications of HIV.1,2<\/sup><\/p>\n

Haematologists should maintain a high index of suspicion for HIV infection and, from a morphological standpoint, should be aware of the bone marrow changes associated with HIV infection.<\/p>\n

\n

Note:<\/strong> HIV-2 infection is endemic in West Africa (HIV-2 generally takes longer to progress to symptomatic HIV\/AIDS than HIV-1). HIV is often associated with mild to moderate thrombocytopenia (50-150\u00d7109<\/sup>\/l), leukopenia, and anaemia. In sub-Saharan Africa, HIV\/AIDS is now the commonest cause of anaemia, leukopenia, and thrombocytopenia encountered both in patients and in the community.<\/p>\n

\n

The following changes may be seen in the bone marrow of HIV (+) patients with cytopenia:<\/strong>3-6<\/sup><\/p>\n

\u00a0– hypercellularity
\n– dysplastic change including dyserythropoiesis, micro-megakaryocytes, and Pelger-Hu\u00ebt anomaly (Figure 1A)
\n– iron stain consistent with anaemia of chronic disorder (storage iron plentiful with reduced number of sideroblasts)
\n– reactive plasmacytosis (\u22655%), binucleate or even multinucleate plasma cells (Figure 1B)
\n– increased macrophages, haemophagocytosis, non-specific granulomas, lymphoid aggregates
\n– reticulin fibrosis
\n– antiretroviral drug toxicity (e.g. antiretroviral megaloblastic change or hypoplasia)
\n– hypocellular marrow and gelatinous transformation (in advanced HIV infection)
\n– infiltration by malignant cells (e.g. acute leukaemia, DLBCL, Burkitt\u2019s lymphoma, Hodgkin\u2019s lymphoma, Castleman’s disease)
\n– morphological evidence of persistent parvovirus B19 infection i.e. red-cell aplasia\/hypoplasia, giant proerythoblasts (‘lantern cells’)
\n– opportunistic pathogens<\/p>\n

\"\"<\/p>\n

Figure 1.<\/strong> Bone marrow changes in \u0397\u0399V infection. A. Dysplastic megakaryocyte (arrow) and dyserythropoiesis (*). B. Increased reactive plasma cells with mature nucleus.<\/p>\n

\n

Note: nuclear immaturity and plasmablasts are uncommon in reactive plasmacytosis \u2260 plasma cell dyscrasias. Striking bone marrow plasmacytosis in an unwell, febrile HIV (+) patient may indicate Castleman’s disease.<\/p>\n

\n

Opportunistic pathogens that involve the bone marrow include:<\/strong>1-7<\/sup><\/p>\n

leishmaniasis
\n\u039c<\/em>ycobacterium avium <\/em>(pseudo-Gaucher cells filled with acid-fast bacilli)
\n\u039c<\/em>ycobacterium tuberculosis
\n<\/em>\u03a4<\/em>oxoplasma
\n<\/em>\u0397<\/em>istoplasma
\n<\/em>Penicillium <\/em>(in South-East Asia)
\nrarely other fungi (Cryptococcus<\/em>, Candida<\/em>, Pneumocystis<\/em>, Microsporidia\/Encephalitozoon, Blastomyces<\/em>), and trypanosomes (T. brucei<\/em> and T. cruzi<\/em>)<\/p>\n

Note: tuberculosis is endemic throughout the tropics.<\/p><\/blockquote>\n

Mycobacteria cannot be stained with Giemsa (or Gram\u2019s stain) because their thick lipid-rich cell wall prevents stain penetration. With fine focus adjustments, mycobacteria may rarely be visualised in Giemsa stained preparations as unstained, refractile, rod-like structures sometimes called \u2018ghost bacilli\u2019 or \u2018phantom bacilli\u2019 (arrow), as shown in Figure 2. This case represents an unusual diagnosis, but one that should always be borne in mind when one sees an immunosuppressed patient with pancytopenia. It is worth remembering that miliary tuberculosis may cause myelophthisic changes (leukoerythroblastosis in the blood film and necrotising granulomas with Langhans\u2019 giant cells in the bone marrow) and thrombocytopenia.<\/p>\n

\"\"Figure 2.<\/strong> Mycobacterium tuberculosis identified on bone marrow aspiration as \u1ffeghost bacilli\u1fbf (arrow).<\/p>\n

Tips:<\/strong>
\n– maintain a high index of suspicion for HIV and tuberculosis (especially in migrants from high-incidence countries)<\/strong><\/em>
\n– haematological disorders may be the presenting manifestation of HIV infection<\/strong><\/em>
\n– dysplastic changes and cytopenia (\u2018myelodysplasia\u2019) in young people \u2192 consider HIV infection<\/strong><\/em>
\n– severe anaemia in HIV (+) patients should prompt investigation for concomitant tuberculosis<\/strong><\/em>
\n– chronic fever, anorexia, weight loss, splenomegaly and generalised lymphadenopathy in immunocompromised patients should raise the suspicion of tuberculosis<\/strong><\/em>
\n– in immunocompromised patients with the triad: fever, pancytopenia and splenomegaly \u2192 request special stains for organisms in bone marrow biopsy sections: Giemsa, Ziehl-Nielsen, periodic acid-Schiff (PAS), Gomori or Grocott, and Gram stain, as seen in Figure 3.<\/strong><\/em><\/p>\n

\"\"
\nFigure 3.<\/strong> Two HIV (+) patients from India who presented with fever, pancytopenia, splenomegaly, patchy pulmonary infiltrates and generalised lymphadenopathy: Panel A shows disseminated \u039c. avium infection (lymph node biopsy; Ziehl-Nielsen stain). Panel B shows disseminated histoplasmosis (bone marrow biopsy; Gomori\u2019s methenamine silver stain).<\/p>\n

Gomori\u2019s methenamine silver stain is the preferred stain for demonstrating fungi. Certain fungi demonstrated by Gomori\u2019s stain do not stain well with PAS which should be used as a secondary approach to enhance morphological detail. All Gram (+) bacteria, including the actinomycetes e.g. Actinomyces<\/em>, Nocardia<\/em> and mycobacteria stain with Gomori\u2019s as do some encapsulated Gram (-) bacteria e.g. Klebsiella<\/em>\u00a0spp<\/em>. Bacteria that have been treated with antibiotics before tissue sampling may not be well stained with Gram, but they often retain their Gomori positivity. Gomori\u2019s stain also highlights the intracytoplasmic inclusions of CMV-infected cell and the polar bodies of microsporidia.<\/p>\n

References<\/strong><\/h5>\n
    \n
  1. Cook GC, Zumla AI. Manson\u2019s tropical diseases. 22nd ed. London: \u0395lsevier Saunders; c2008.<\/li>\n
  2. Farrar J, Hotez P, Junghanss T, Kang G, Lalloo D, White N. Manson\u2019s tropical diseases. 23rd ed. London: \u0395lsevier Saunders; c2014.<\/li>\n
  3. Kaushansky K, Lichtman MA, Prchal JT, Levi MM, Press OW, Burns LJ, et al. William\u2019s hematology. 9th ed. New York: McGraw Hill Education; c2015.<\/li>\n
  4. Hoffbrand AV, Higgs DR, Keeling DM, Mehta AB. Postgraduate haematology. 7th ed. Oxford: Wiley Blackwell; c2016.<\/li>\n
  5. Bain BJ, Clark DM, Wilkins BS. Bone marrow pathology. 4th ed. London: Wiley Blackwell; c2011.<\/li>\n
  6. Hoffbrand VA, Pettit JE, Vyas P. Color atlas of clinical hematology. 4th ed. Philadelphia: Mosby Elsevier; c2010.<\/li>\n
  7. Chavda S, Liapis K. Detection of mycobacteria in MGG\u2011stained bone marrow smears. Int J Hematol. 2016 Feb;103(2):115-6.<\/li>\n<\/ol>\n","protected":false},"excerpt":{"rendered":"

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