Sulfhemoglobin under the spotlight - Detection and characterization of SHb and HbFeIII-SH.

Sulfhemoglobinemia is an incurable disease caused by an overdose of sulfur-containing drugs with oxidizing properties. Its diagnosis remains hindered due to the similarity of symptoms to other pathological state - methemoglobinemia, as well as contradictory information on the structure and characteristics of sulfhemoglobin. Herein, we present sulfhemoglobinemia model on living functional human erythrocytes, designed to recreate processes which could take place in a patient body in order to complement missing information and highlight distinctiveness of two hemoglobin (Hb) adducts formed after interaction with sulfur donors. Employed techniques, UV-Vis absorption, Raman, Fourier transformed infrared (FT-IR) and electronic circular dichroism (ECD) spectroscopies, allowed to distinguish and characterize Hb adduct with sulfur atom bounded directly to the iron ion (HbFeIII-SH), and irreversibly connected to the porphyrin ring (SHb - sulfhemoglobin). Presented herein results provided also new evidence on formation of both these hemoglobin adducts inside functional erythrocytes under oxidative conditions and during sulfur-containing drug presence, what can be further translated into future physiological studies. Moreover, we found that sulfur attachment to the porphyrin ring altered Hb structure and lead to changes in protein packing inside RBCs, eventually. Interestingly, measurement of blood drop smear by Raman spectroscopy occurred the most accurate method to differentiate HbFeIII-SH and SHb, indicating potential of this technique in sulfhemoglobinemia diagnosis.

On the noninvasive optical monitoring and differentiation of methemoglobinemia and sulfhemoglobinemia.

There are several pathologies whose study and diagnosis is impaired by a relatively small number of documented cases. A practical approach to overcome this obstacle and advance the research in this area consists in employing computer simulations to perform controlled in silico experiments. The results of these experiments, in turn, may be incorporated in the design of differential protocols for these pathologies. Accordingly, in this paper, we investigate the spectral responses of human skin affected by the presence of abnormal amounts of two dysfunctional hemoglobins, methemoglobin and sulfhemoglobin, which are associated with two life-threatening medical conditions, methemoglobinemia and sulfhemoglobinemia, respectively. We analyze the results of our in silico experiments and discuss their potential applications to the development of more effective noninvasive monitoring and differentiation procedures for these medical conditions.

Acrocyanosis from phenazopyridine-induced sulfhemoglobinemia mistaken for Raynaud phenomenon.

Rheumatologists are often asked to evaluate patients with Raynaud phenomenon. Occasionally, an alternate explanation is revealed such as acrocyanosis. Methemoglobinemia and sulfhemoglobinemia are rare causes of cyanosis that can be medication-induced. Both are known complications of therapy with phenazopyridine. We report an unusual case of a 45-year-old woman in whom sulfhemoglobinemia from chronic therapy with phenazopyridine was misdiagnosed as due to Raynaud phenomenon and limited scleroderma. This case illustrates the importance of taking into account medication-related adverse events when evaluating patients with Raynaud-like phenomenon.

Identification of sulfhemoglobinemia after surgical polypectomy.

Sulfhemoglobinemia (SHb) is an uncommon cause of cyanosis that is predominantly drug-induced in adults. We report an unusual case of sodium sulfate-induced sulfhemoglobinemia in a 61-year-old woman after surgical polypectomy. Fractional hemoglobin derivates were assayed by spectrophotometry and high-performance liquid chromatography. The SHb ratio was 8.6% in the first sample and 3.77% a month later measured by spectrophotometry. In the blood hemolysate, a new peak was identified as SHb with high-performance liquid chromatography (HPLC). HPLC showed the presence of 9.37% SHb in the first sample and 4.88% a month later. After removing the suspected toxic agent the cyanosis decreased significantly. The findings underline the importance of routine SHb detection in cyanosis of unknown origin especially in emergency cases.

Phenazopyridine-induced sulfhemoglobinemia.

OBJECTIVE: To report a case of sulfhemoglobinemia in a patient receiving phenazopyridine for a urinary tract infection. CASE SUMMARY: A 63-year-old white woman presented to the emergency department with complaints of fatigue and bluish discoloration of her body that had gradually progressed over the previous 6-8 weeks. About 4 months prior to presenting to the emergency department, she had started taking phenazopyridine, an over-the-counter medication for symptoms of dysuria. Because the cyanosis did not improve after the patient received oxygen and methylene blue, sulfhemoglobinemia was suspected and confirmed by spectrophotometer analysis. DISCUSSION: Sulfhemoglobin is a green-pigmented molecule containing a sulfur atom in one or more of the porphyrin rings. It is a rare cause of cyanosis, which is usually drug induced. Sulfhemoglobinemia is suspected when a cyanotic patient has normal to near-normal oxygen tension, laboratory reports of elevated methemoglobin, and does not respond to methylene blue therapy. Sulfhemoglobinemia is relatively rare, despite the widespread use of drugs that have been reported to cause it. Predisposing factors, such as chronic constipation, present in our patient, have been suggested as a source of hydrogen sulfide. CONCLUSIONS: This case of sulfhemoglobinemia, which occurred after the patient took phenazopyridine, is considered a probable adverse event according to the Naranjo probability scale.

Pseudomethemoglobinemia: a case report and review of sulfhemoglobinemia.

OBJECTIVES: To see if methemoglobin could potentially be misdiagnosed and the limitation of present cooximeters. PATIENT: A 17-year-old girl who overingested a combination of cimetidine, acetaminophen, ibuprofen, and naproxen in a suicide attempt. METHOD: Use of pulse co-oximeters to aid in the diagnosis of suspected sulfhemoglobinemia. RESULTS: Diagnosis of sulfhemoglobinemia achieved with final confirmation made with gas chromatography. Patient steadily improved with supportive care. CONCLUSIONS: There is a potential for the diagnosis of methemoglobin with some of the limitations of present co-oximeters. The laboratory diagnosis of sulfhemoglobinemia can be difficult to make.

Phenacetin-induced sulfhemoglobinemia: report of a case and review of the literature.

Phenacetin-induced sulfhemoglobinemia was diagnosed in a middle-aged woman with a 6-month history of cyanosis and a 10-year history of ingestion of analgesics. The laboratory and clincial diagnosis of sulfhemoglobinemia and methemoglobinemia are discussed. The reviewed medical literature suggests that the cyanosis of chronic phenacetin or acetanilid use is generally due to sulfhemoglobinemia rather than methemoglobinemia.