Critical Thinking

Background: of immune reconstitution inflammatory syndrome (IRIS) following

Background:

To our knowledge Sarcoidosis has never been described as a cause of interstitial lung pathology associated with HIV in Saudi Arabia. In fact it has been rarely implicated as an association in literature worldwide and was more commonly reported as a part of immune reconstitution inflammatory syndrome (IRIS) following Highly Active Anti-Retroviral Therapy (HAART)1. Sarcoidosis is believed to be a rarity in Native Saudi with the earliest mention of the disease in 1993 by Khan J and colleagues where they reported twenty cases followed up in their tertiary care center 2. The epidemiology of sarcoidosis in Saudi Arabia or Middle East in general is quite lacking and incidence and prevalence is yet unknown. The current literature available suggest that the most common presentations of sarcoidosis in native Saudis are dyspnea (48.64%), cough (44.59%), joint pain (39.18%), weight loss (28.37%) and fever (24.32%) as reported in the three studies done in central, western and eastern regions of Saudi Arabia in 1993, 1999 and 2011 respectively Table 12,3,4. Although relative lack of cardiac, parotid, eye, and central nervous system involvement has been observed, nevertheless, clinical presentation is comparable to that of western world 3,4. The most common stage was found to be stage II (51.35%) compared to stage I in western world 2,3,4. When it comes to difference in clinical presentation and pathology of sarcoidosis identified in HIV infected patients to that of HIV non-infected patients there was no significant difference. Nevertheless, it is established that CD4+ > 200 associated with worsening of symptoms probably due to activation of immune system while CD4+ < 200 is associated with improvement of symptoms for the opposite reason5. Unfortunately there is lack of data of such correlation in Saudi Arabia and comparison to the west cannot be made at the time being. Material and Methods: Search through PubMed with the keyword of Sarcoidosis, HIV, AIDS  was done to find and review similar reported cases worldwide and in Saudi Arabia. Around three cases were mentioned in literature were Sarcoidosis was complicated by or was diagnosed prior to HIV identification worldwide 6. No cases of sarcoidosis and HIV association were reported in Saudi.

Case Report:

A 55-year-old native Saudi male who is known to have hypothyroidism diagnosed 3 years ago, history of 60 pack-year cigarette smoking. He presented to our medical services with 2 year history of weight loss and fatigability. They were associated with cyclic fever occurring every two to three days ranging between 37.4oC to 38oC and productive cough of yellowish sputum. On further questioning patient admit that he has been suffering from persistent right neck swelling and tongue pain for 9 years, vague abdominal pain for 8 years. He has multiple emergency department (ED) visits for these symptoms with no apparent cause identified after extensive investigation including Abdominal Ultrasound and Contrast enhanced computed tomography (CT) Neck, Chest and Abdomen. The Ultrasound showed enlarged liver and hemangioma. While the contrast enhanced CT Neck and Chest showed multiple bilateral neck lymphadenopathy, Aortic arch atherosclerotic calcification, no mediastinal lymphadenopathy or lung pathology. Enhanced Abdominal CT was unremarkable.

 

On examination patient was alert, conscious, oriented. He was distressed, appeared ill, pale, with temporal muscle wasting, and generalized muscle weakness. He was vitally stable saturating well on room air. Cardiovascular examination was unremarkable, chest was clear to auscultation with no adventitious sounds, abdominal examination revealed right upper quadrant fullness and mildly tender hepatosplenomegaly. Patient was admitted as a case of unexplained weight loss, possible COPD, and hepatosplenomegaly in light of possible extrapulmonary Tuberculosis (TB) for further evaluation.

 

CXR showed multiple small lung nodules the largest was in the lower right lung zone .

figure1. Blood work showed microcytic hypochromic anemia with RDW of 21.6, Leukopenia with neutriopenia and lymphopenia. Iron study showed ferritin of 613 ug/l, normal transferrin saturation, low serum iron, CRP of 33.4 mg/L, Amylase of 324 u/l, Low normal calcium. ESR of 116 Table 2. Abdominal Ultrasound showed hepatosplenomegaly and redmonstration of hemangioma. CT Abdomen with contrast showed hepatosplenomegaly with multiple cystic lesions in the liver figure 2. The findings were not conclusive and we could not reach a satisfactory diagnosis therefore, and after lengthy discussion with the patient we decided to look somewhere else. At this time patient admitted having risky sexual behavior outside marriage boundaries which he denies at admission. Thus, we began extensive serology work-up in addition to Contrast Enhanced Chest CT.

 

Contrast enhanced CT Chest showed significant interval developmental changes, multiple enlarged mediastinal lymph nodes, multiple pulmonary nodules mainly in the right side; the largest one seen in the superior segments of the right lower lobe with speculated margin surrounded multiple satellite nodules and redemonstration of previously seen subpleural cyst in the right lower lobe figure3. The differential diagnosis was broadened to include bronchogenic carcinoma owing to his high smoking index and infectious disease such as TB, CMV, HIV and HIV-related infection were suspected. After gaining patient informed consent CT-Guided lung biopsy was obtained for definitive diagnosis while awaiting serology and septic screen results. Full septic screen and serology yielded negative results. However, CMV IgM +ve, HIV result were pending. The biopsy taken showed Chronic interstital pneumonitis with non-necrotizing granulomas and fibrosis. It was negative for acid-fast bacilli, fungal organisms, atypia and malignancy figure 4,5,6,7. The daignosis of sarcoidosis at this time was strongely suspected since we exhausted other possible diagnosises and therefore, patient was referred to ophthalmology, cardiology to exclude sarcoid-related diseases and to Rheumatology for their expert opinion. Rheumatology team started sarcoidosis treatment with pulse steroid. Patient condition started to improve and was discharged home and to come back for his HIV result, PFTs and further assessment on the following week. PFTs testing showed restrictive lung pathology in keeping with his diagnosis. HIV was positive however, his CD4+ count was as low as 11 I/mm3 which is not in keeping with available literature that established the CD4+ dependency of manifesting sarcoidosis in HIV patient making his presentation extremely atypical and even more challenging. ID team was informed and he was started on HAART. His symptoms of sarcoidosis did not worsen with improvement of his CD4+ count and his IRIS manifested as CMV retinitis rather than worsening of sarcoidosis symptoms.

 

Discussion:

Sarcoidosis is a diagnosis of exclusion. Sarcoidosis is rare with estimated incidence of 6 cases in 100,000 person per year in the US 07. In Saudi Arabia there has been only 4 major studies on sarcoidosis featuring approximately 180 cases. However incidence nor prevalence has not been studied yet. The association of HIV has been discussed in multiple publication in the western world and patient typically present with HIV and after initiation of HAART sarcoidosis and other autoimmune diseases became unmasked by the reactivation of patient immune system9 Our patient was in his fifties which is in keeping with sarcoidosis bimodal peak. The history of smoking and the nature of his complaints that lack dyspnea and cough combined with lack of findings in chest examination are extremely atypical. The changes found in the Plain Chest X-ray were easily link to undiagnosed COPD in light of his smoking history and was not as probative as his abdominal symptoms which were more alarming. Chronic sepsis, abdominal malignancy, and extrapulmonary TB were on top of our differential diagnosis. However, when his septic screen, enhanced abdominal computed tomography, and PPD testing were not conclusive  led us to look somewhere else. Early cuts of Abdominal enhanced computed tomography lead us to pursue a chest CT and luckily enough we had a previous CT to compare with. The developmental changes and enlarged lymph nodes found in the new contrast enhanced chest Computed Tomography encourage us to go for lung biopsy to exclude malignancy since features of COPD were not found. Lung biopsy results showed non-caseating granuloma figure 4,5,6,7 However some of his symptoms were not conveniently explained by sarcoidosis (e.g. Pancytopenia, HSM, liver mass that was not granulomatous and cyclic fever) so HIV and other viral serology testing was done. The result came out positive after patient has been started on sarcoidosis therapy and discharged. Interestingly his CD4+ was low and  according to available literature sarcoidosis typically would not be observed with low CD4+ count due to its dependency on it.  Patient CD4/CD8 ratio was depressed however the ratio has many limitation and no longer used to diagnose sarcoidosis. His symptom did not worsen after initiation of HAART and subsequent increase in CD4+ count 8. He kept on showing improvement of symptoms, which may be attributed to the ongoing treatment of corticosteroids. This case report present the first case of histologically proved sarcoidosis that was diagnosed in a patient with low CD4+ HIV in Saudi Arabia and Middle East.

 

Conclusion:

Sarcoidosis is still under diagnosed and has not been properly studied in Saudi Arabia. Sarcoidosis associated with HIV is quite rare and diagnosis is challenging and the association between the two pathology need to be studied in Saudi Arabia. Multidisciplinary effort and cooperation between different medical and surgical services is important for timely diagnosis and appropriate management. Outcome of Sarcoidosis in HIV infected is similar to that of non-HIV infected patients. Involving patient and his beloved ones improve the dynamic of diagnosis and management dramatically.