Conditions of the Lymph System

2. Objectives Describe the various etiologies that cause lymphadenopathy Describe the clinical presentation of persistent generalized lymphadenopathy (PGL) List the diagnostic criteria for PGL Describe features of lymph nodes that indicate further evaluation Make a differential diagnosis using a case study approach

3. Overview Swelling of lymph nodes is a frequently encountered symptom It is important to carry out a careful history and physical exam The cause often becomes obvious, but in more complicated cases, laboratory tests and lymph node biopsy may be necessary to establish a definitive diagnosis

4. Major Pathogens HIV- related persistent generalized lymphadenopathy (PGL) Opportunistic infections tuberculous lymphadenitis, CMV, toxoplasmosis, infections with Nocardia species, fungal infections (histoplasmosis, penicilliosis, cryptococcus, etc.) Reactive Lymphadenopathy pyomyositis, pyogenic skin infections, ear, nose, and throat (ENT) infections STIs syphilis, inguinal lymphadenopathy due to donovanosis, chancroid or lymphogranuloma venereum (LGV) (see WHO or MSF guidelines) Malignancies lymphoma, Kaposi’s sarcoma

6. Persistent Generalized Lymphadenopathy (PGL) Lymph nodes larger than 1.5 cm in diameter in 2 or more extrainguinal sites of 3 or more months duration Nodes are non-tender, symmetrical, and often involve the posterior cervical, axillary, occipital, and epitrochlear nodes

7. Where possible, do a CBC (FBC) and chest x-ray before making a diagnosis of PGL  Hilar or mediastinal lymphadenopathy on CXR Diagnostics

8. Management and Treatment No specific treatment for PGL

9. Unique features, Caveats Develops in up to 50% of HIV-infected individuals Up to one-third do not have any other symptom on presentation (WHO clinical stage 1) In HIV-positive patients, PGL is a clinical diagnosis. No further examinations are necessary, unless there are features of another disease  PGL may slowly regress during the course of HIV infection and may disappear before the onset of AIDS

10.  Cervical nodes most commonly involved Usual course of lymph node disease is as follows: Firm, discrete nodes ? fluctuant nodes matted together ? skin breakdown, abscesses, chronic sinuses ? healing and scarring

11. Fine-needle aspiration of the involved lymph node   Extra-thoracic lymph node aspiration   Positive smears for acid-fast bacilli on fine-needle aspirates of the involved lymph nodes (high rate in HIV patients)   In smear-negative pulmonary TB, it is worthwhile aspirating extra-thoracic lymph nodes to confirm diagnosis of TB (80% positive) Diagnostics

13. Management and Treatment Treatment should be started following the national TB Guidelines. For further details, see Part A Module 2, Session 3.

14. Unique features, Caveats One of the most common forms of extra-pulmonary TB in HIV patients Fluctuant cervical nodes that develop over weeks to months without significant inflammation or tenderness suggest infection with M. tuberculosis, atypical mycobacteria, or scratch disease (Bartonella henselae). In severe immunocompromised patients, tuberculosis lymphadenopathy may be acute and resemble acute pyogenic lymphadenitis Miliary TB is an important consideration in patients with generalized lymphadenopathy

15. Nocardiosis Presenting Signs and Symptoms Clinical Symptoms may evolve Chronic lymphadenopathy Abscesses (skin, pulmonary, etc.)

16. Fine-needle aspiration of the involved lymph node Organism may stain weakly on acid-fast staining. The organisms are different from the Koch bacilli because of their thread-like filaments Nocardia organisms are easily recognized on Gram stain Diagnostics

17. Management and Treatment TMP/SMX 10/50 mg/kg bid or minocycline 100 mg bid combined with amikacin 15-25 mg/kg daily or ceftriaxone 2 gm daily combined with amikacin. The use of aminoglysides should be limited to 2 weeks

18. Unique features, Caveats While norcardiosis is a rare cause of lymphadenitis in immune-competent patients, the diagnosis should be considered in HIV-infected patients with chronic lymphadenopathy and abscesses (skin, pulmonary, etc.)

19. Fungal infections (histoplasmosis, penicilliosis, cryptococcosis)  Clinical Symptoms may evolve Fever Lymphadenopathy Often skin lesions or lung lesions

20. Biopsy for histology and culture of skin lesions or lymph nodes often reveals the diagnosis Diagnostics

21. Management and Treatment Initial treatment for histoplasmosis and penicillinosis: amphotericin B for moderate-to-severe cases Itraconazole 200 mg daily is the preferred lifelong maintenance therapy If itraconazole is not available, use ketaconazole 400 mg daily For cryptococcosis give: amphotericin B (IV) o.7 mg/kg daily for 14 days, followed by fluconazole 400 mg daily for 8-10 weeks. After that, maintenance therapy consists of fluconazole 200 mg once a day

22. Secondary syphilis Clinical Symptoms may evolve Generalized painless lymphadenopathy Maculo-papular, papular, or pustular rash on entire body, especially on palms and soles Highly infectious lesions on mucous membranes (lips, mouth, pharynx, vulva, glans penis) which are silvery grey superficial erosions with a red halo and not painful unless there is a secondary infection. 40% of these patients will have CNS involvement with headache and meningismus 1-2% will develop acute aseptic meningitis

23. CSF exam  CSF shows increased protein and lymphocytic pleocytosis Diagnostics

24. Management and Treatment Although there is some doubt about treatment efficacy in HIV patients, the CDC recommends the same treatment for primary and secondary syphilis as in HIV-negative individuals: benzathine penicillin 2.4 million units IM single dose In case of penicillin allergy, give: doxycycline 100 mg PO bid for 21 days or ceftriaxone 1 gm IM/IV daily for 14 days

25. Lymphoma and Kaposi’s Sarcoma  Presenting Signs and Symptoms Clinical Symptoms may evolve Lymphadenopathy Characteristic skin lesions in oral cavity, GI tract, and respiratory tract

28. Diagnosis confirmed by histopathology Diagnostics

29. Management and Treatment For treatment and management, see Part One, Module 2/ Session 11